Bombyx mori, as a lepidoptera model insect, has numerous advantages in life science and can be used as an important model in various research areas. However, few nucleases on RNA insensitivity or virus defense have been studied in B. mori. In this study, we identified a protein asteroid (BmAst) in silkworm B. mori, containing the PIN domain and XPG domain. BmAst gene was highest expressed in hemocytes and fat body of the 5th larvae. The BmAst gene expression was significantly induced by Bombyx mori nucleopolyhedrovirus (BmNPV) or dsRNA. By interference with BmAst gene expression, the proliferation of BmNPV in B. mori was significantly increased, whereas the survival rate of silkworm larvae was significantly lower when compared with the control. Our results indicate that BmAst is involved in silkworm resistance to BmNPV infection.Nucleases are highly diverse enzymes that cleave phosphodiester bonds of nucleic acids with highly diverse enzymes. A widespread superfamily of nucleases contains PIN-like domains, which are identified in eukaryotes and prokaryotes. The domesticated silkworm Bombyx mori nucleopolyhedrovirus (BmNPV) infection in silkworm B. mori has been found. In this study, a protein asteroid (BmAst) containing the PIN domain and XPG domain was identified in silkworm B. mori. BmAst gene was highest expressed in hemocytes and fat body of the 5th instar larvae, and high expression in the pupa stage. The transcriptional levels of the BmAst gene in 5th instar larvae were significantly induced by BmNPV or dsRNA. After knocking down BmAst gene expression by specific dsRNA, the proliferation of BmNPV in B. mori was increased significantly, whereas the survival rate of larvae was significantly lower when compared with the control. Our findings indicate that BmAst is involved in silkworm resistance to BmNPV infection.Nuclease is a type of protein that degrades nucleic acids, which plays an important role in biological processes, including RNA interference efficiency and antiviral immunity. However, no evidence of a link between nuclease and  Cylas puncticollis [Leptinotarsa decemlineata [Spodoptera litura [The metabolism of nucleic acids plays an important role in biological processes in all kingdoms of life. Nucleases are highly diverse enzymes that cleave phosphodiester bonds of nucleic acids with highly diverse enzymes . DNA/RNAticollis , Coloradmlineata , tobaccoa litura .2+-dependent exonucleases [Ostrinia furnacalis, contains a PIN domain at the 5′-end and encodes a nuclease that contributes to RNAi insensitivity in lepidoptera insect order [PIN-like domains, annotated type IV pili twitching motility protein , constitute a widespread superfamily of nucleases . PIN domucleases . The PINucleases . A lepidct order .Bombyx mori, as a lepidoptera model insect, has numerous advantages in life science and can be used as an important model in various research areas [B. mori gene functional analysis and the development of silkworms as bioreactors [Bombyx mori nucleopolyhedrovirus (BmNPV) is a major pathogen in silkworm breeding that causes serious economic loss to the sericulture industry worldwide [B. mori have been reported against BmNPV infection by overexpression in transgenic silkworms, such as PEPCK, hycu-ep32, Bmlipase-1, and BmHsp19.9 [IE-0 and IE-2, lef8 and lef9, BmFerHCH, and BmATG13 [The domesticated silkworm ch areas ,15. Genereactors . Howeverorldwide . BmNPV iorldwide . ImprovimHsp19.9 ,21,22. A BmATG13 ,24,25,26 BmATG13 . Spry is BmATG13 . HoweverB. mori (BmAst) was identified as a nuclease belonging to the PIN superfamily. The gene expressions of BmAst were analyzed in the B. mori larvae treated by dsRNA or BmNPV. The relationship between BmAst expression and proliferation of BmNPV in B. mori was measured by RNA interference. Our results showed that BmAst gene expressions were significantly induced by BmNPV or dsRNA. After knocking down the BmAst gene, the proliferation of BmNPV in B. mori was significantly increased, whereas the survival rate of silkworm larvae was significantly lower compared with the control. Our results suggest that BmAst has a role in silkworm resistance to BmNPV infection.Several techniques have been developed as a result of research on the interaction between viruses and the siRNA pathway, including methods for detecting hidden viruses in insect cell lines, improving baculovirus expression systems, and the potential application of virus-induced gene silencing (VIGS) for the control of pests and diseases . RNAi paBombyx mori (Nistari strain) was maintained in our laboratory. The B. mori larvae were reared with fresh mulberry leaves at 25 ± 1 °C under a 12L:12D photoperiod and 60 ± 10% relative humidity. BmNPV T3 strain, bacterial , or fungus (Beauveria bassiana) were stored at −20 °C in our laboratory and purified according to the protocol reported [The experimental reported .B. mori tissues using a TRIzol reagent  and reverse-transcribed into complementary DNA (cDNA) using a TransScript® First-Strand cDNA Synthesis SuperMix (Transgen) according to the manufacturer’s instructions. Based on the sequence at GenBank (GenBank No. XM_021350017.2), a pair of primers (BmAst-F and BmAst-R) , and then sequenced by Sangon Biotech. The conserved domains of predicted BmAst protein were searched at the NCBI (http://blast.ncbi.nlm.nih.gov/Blast.cgi (accessed on 11 June 2023)) and Pfam (http://pfam.xfam.org/ (accessed on 11 June 2023)). Homologous sequences of BmAst protein in insects were obtained from the NCBI. The phylogenetic tree was constructed using the neighbor-joining method by MEGA 7 and was tested for reliability using 1000 bootstrap repetitions [Total RNA was isolated from BmAst-R)  was desietitions .B. mori using a TRIzol reagent and reverse-transcribed into cDNA using ReverTra Ace® qPCR RT Master Mix with gDNA Remover . For quantitative real-time polymerase chain reaction (qRT-PCR) analysis, the diluted cDNAs (10×) were used as the template, and the BmActin A3 gene (GenBank No. U49854) was used as the internal control gene [https://primer3.ut.ee/ (accessed on 11 June 2023)) based on their known sequences. A melting curve (65–95 °C) was analyzed to test the unique and specific PCR product for each reaction. The result data were analyzed using the 2−ΔΔCt method [Total RNA was extracted from different tissues of rol gene . qRT-PCRt method . All theBmAst gene in B. mori larvae. The head and six tissues  were collected. For the developmental stages expression analysis of BmAst, egg stages, the whole body of B. mori in five larval stages , pupa, and moth were collected. The expressions of BmAst mRNA were measured by qRT-PCR.The day 3, fifth-instar larvae were dissected on ice to analyze the tissue expression of the B. mori larvae  were injected with the heated-inactivated Gram-negative bacterium , a Gram-positive bacterium , fungus , virus /mL) or phosphate-buffered saline buffer , respectively. The fat body of B. mori was collected at 1.5, 3, 6, 12, 24, and 48 h post-infection by dissecting the larvae. All the experiments were carried out in three biological replicates. The expressions of BmAst mRNA were measured by qRT-PCR. Because of the low expression of BmActin A3 after microbial infection, the B. mori glyceraldehyde-3-phosphate dehydrogenase gene  was used as an internal control for microbial infection [nfection ,34,35.BmAst or EGFP were synthesized and purified by the T7 RiboMAXTM Express RNAi System  according to the manufacturer’s instructions. The target gene-containing plasmids were used in the PCR procedure. The specific primers for BmAst or EGFP containing a T7 promoter sequence  were injected with dsEGFP  to test the dsRNA effect on BmAst gene expression. The PBS was injected as a control. After 4 h injection, the fat body was collected for analyzing BmAst expression by qRT-PCR. The RNAi core gene, Ago-2 (GenBank No. NM_001043530) and Dicer-2 (GenBank No. NM_001193614.1) in B. mori, which can be induced by dsEGFP, were analyzed.B. mori larvae (first day of 5th instar) were injected with dsBmAst , or dsEGFP  as a control. After 24 h or 48 h of dsBmAst injections, the mRNA expression of BmAst in B. mori fat body was analyzed by qRT-PCR. The larvae were fed with BmNPV  on mulberry leaves after 48 h dsBmAst injection. B. mori larvae continued feeding with fresh mulberry leaves. The larvae challenged with BmNPV only served as controls. The mortality of silkworms was calculated after being infected with BmNPV. Each biological sample (30 larvae) was carried out in three replicates.B. mori fat body after 48 h BmNPV feeding was extracted using Ezup Column DNA Extraction Kit  for analyzing BmNPV proliferation. DNA concentrations were tested by a NanoDrop instrument. The primers for the VP39 gene (GenBank No. NC_001962.1) were used to determine BmNPV proliferation  in B. mori by qPCR. Primer information used for qPCR is shown in DNA from the p < 0.05 was considered a significant difference (* p < 0.05 and ** p < 0.05).The data in this study were presented as the mean ± standard error. Data were analyzed using a one-way analysis of variance analysis (ANOVA) (Tukey’s test) by DPS software . p < 0.0B. mori (BmAst) contains an open reading frame of 2241 base pairs encoding a 746-residue polypeptide (GenBank No. XM_021350017.2). SignalP5.0 analysis shows there is no signal peptide in the BmAst protein, indicating that BmAst protein may not be secreted outside the cell and belongs to intracellular protein. The predicted molecular weight of the protein is 87.72 kDa, and the theoretical isoelectric point is 6.77. The conserved domain analysis shows that the protein contains a PIN (PilT N terminus) domain and an XPG (Xeroderma pigmentosum complementation group G) domain  domain A. The ph species B.BmAst gene is widely expressed in all tested tissues of 3-day-old fifth-instar larvae, with the highest expression level in hemocytes and fat body and the lowest expression in the epidermis , B. thuringiensis (Gram-positive bacterium), and B. bassiana (Fungus) compared with the control group injected with PBS, and their expression level remain almost unchanged  pathway are also detected by qRT-PCR. The results show that exogenous dsRNA can significantly up-regulate the expression of BmAst compared with the control . It belongs to the PIN domain superfamily, which is one of the largest and most diverse nuclease superfamilies [O. furnaclis and C. elegans. REase with a PIN domain at the 5′-end in O. furnaclis, could degrade various types of nucleic acids, such as dsRNA, dsDNA, ssRNA, ssDNA, and plasmid [C. elegans is involved in regulating the persistence of RNA interference [In this study, we reported the characteristic of a protein asteroid in families . The PIN plasmid . The SMG plasmid . Smg-5 wrference . Nucleasrference  and can rference .BmAst gene was up-regulated by dsRNA and BmNPV and had no obvious response after larvae were infected with a Gram-positive bacterium, Gram-negative bacterium, or a fungus. This suggests that BmAst may be involved in RNAi efficiency and the defense against BmNPV infections. The dsRNA stability in insects is connected to RNAi efficiency, but the RNAi efficiency was variable in different species. Knockdown of nuclease activity in the insect gut enhanced RNAi efficiency is variable in the Colorado potato beetle, Leptinotarsa decemlineata, but not in the desert locust, Schistocerca gregaria [Drosophila is often associated with higher mortality rates [dcr-2 null mutation Drosophila, inoculation with the same dose of FHV resulted in 60% mortality by 6 dpi and 95% by 15 dpi [Our study showed that the gregaria . Nucleasgregaria . Recent ty rates . Flock hy 15 dpi . RNA sily 15 dpi .BmAst gene in silkworms, the proliferation of BmNPV was significantly increased, and the mortality rate after BmNPV infection was also increased. In conclusion, BmAst could indeed inhibit the proliferation of the BmNPV virus, which plays a crucial role in antiviral infections. The Dicer2 gene in the RNAi pathway was involved in the anti-BmNPV virus in B. mori [Dicer2 gene, as an RNAi component, has also been reported to affect the replication of other DNA viruses, such as Invertebrate iridescent virus 6 (IIV-6) [Helicoverpa armigera single nucleopolyhedrovirus (HaSNPV) [D. melanogaster, the RNA-silencing endonuclease Argonaute 2 mediates specific antiviral immunity [Drosophila bidirectionally transcribed IIV-6 DNA genome-specific AT-rich regions to generate dsRNA. Both replicative and naked IIV-6 genomes triggered the production of dsRNA in Drosophila cells. So, the RNAPII complex recognized invading viral DNA to synthesize virus-derived dsRNA, which activated the antiviral siRNA pathway in Drosophila [By knocking down the expression of the  B. mori . The Dic (IIV-6) , Helicov(HaSNPV)  and Auto(HaSNPV) . In D. mimmunity . dsRNA iimmunity . RNA polosophila . BmAst mosophila . Therefoosophila .B. mori. Our results provide a target gene to improve virus resistance in B. mori. However, how BmAst affects BmNPV replication and the interaction between BmAst and RNAi pathway was unclear. The mechanism of BmAst involvement in antiviral function by the RNAi pathway will be investigated in the future.Altogether, our results suggest that BmAst protein containing a PIN family domain plays an important role in BmNPV infection in


The human body is colonized by abundant and diverse microorganisms, collectively known as the microbiome. The oral cavity has more than 700 species of bacteria and consists of unique microbiome niches on mucosal surfaces, on tooth hard tissue, and in saliva. The homeostatic balance between the oral microbiota and the immune system plays an indispensable role in maintaining the well-being and health status of the human host. Growing evidence has demonstrated that oral microbiota dysbiosis is actively involved in regulating the initiation and progression of an array of autoimmune diseases.Oral microbiota dysbiosis is driven by multiple factors, such as host genetic factors, dietary habits, stress, smoking, administration of antibiotics, tissue injury and infection. The dysregulation in the oral microbiome plays a crucial role in triggering and promoting autoimmune diseases via several mechanisms, including microbial translocation, molecular mimicry, autoantigen overproduction, and amplification of autoimmune responses by cytokines. Good oral hygiene behaviors, low carbohydrate diets, healthy lifestyles, usage of prebiotics, probiotics or synbiotics, oral microbiota transplantation and nanomedicine-based therapeutics are promising avenues for maintaining a balanced oral microbiome and treating oral microbiota-mediated autoimmune diseases. Thus, a comprehensive understanding of the relationship between oral microbiota dysbiosis and autoimmune diseases is critical for providing novel insights into the development of oral microbiota-based therapeutic approaches for combating these refractory diseases. The human microbiota, which consists of approximately 10–100 trillion symbiotic microorganisms, defines the sum of all microbes forming communities present in any habitat, including the skin, oral cavity, respiratory system, gastrointestinal tract, and urogenital tract . On the Porphyromonas gingivalis can transform arginine to citrulline in proteins via arginine gingipains and peptidylarginine deiminases (PADs) [Aggregatibacter actinomycetemcomitans (Aa) is the key bacterium triggering autoimmune responses in RA, and it is a known periodontal pathogen that can secrete the pore-forming toxin leukotoxin-A (LtxA). LtxA induces the production of citrullinated antigen by abnormally activating citrullinating enzymes in neutrophils [Aa, P. gingivalis, Treponema denticola, and Capnocytophaga. ochracea were found in SLE patients positive for anti-dsDNA antibodies. In particular, antibodies against Aa were significantly associated with SLE disease activity [The oral cavity harbors the second largest and most diverse microbiota after the gastrointestinal tract, with 770 opportunistic, commensal, and pathogenic bacterial species . Many uns (PADs) . The imms (PADs) . Aggregatrophils . In addiactivity .Fig. 1ThOral microbiome is readily accessible and easily sampled, thereby dissecting the composition and function of oral microorganisms is crucial for elucidating the underlying molecular mechanisms for the development of autoimmune diseases. The current review comprehensively covers the pathological changes affecting the bilateral cross-talks between oral microbiota and immune system, which might result in the initiation and progression of autoimmune diseases. We also discussed the major molecular mechanisms that oral microbiota dysbiosis affects autoimmune diseases . The potential therapeutic strategies for balancing the oral microbiota are also focused on, which may provide evidence for the precision management and improvement of the efficacy of oral microbiota-mediated autoimmune diseases.Lactobacilli produce indole-3-aldehyde, and this microbial metabolite stimulates the production of IL-22 and IL17 by activating the aryl hydrocarbon receptor, contributing to the balance of the intestinal mucosal immune system [The microbiota plays a decisive role in the induction, training and functions of the host immune system. Early microbial exposure to infants is essential for regulating and influencing the formation of the immune system . The bace system . Severe e system . Interese system . Similare system . These fe system .Conversely, the immune system also plays a fundamental role in establishing a sustainable and harmonious host-microbial relationship. The immune response to pathogenic microorganisms is the leading cause of host-mediated tissue damage, which might create a microenvironment that is beneficial for microbiota dysbiosis and invasion by pathogenic microbes. For example, the inflammatory response promotes the growth of aerobic bacteria and significantly decreases the survival of resident colonic bacteria, resulting in IBD . DiffereFirmicutes/Bacteriodetes ratio [Bifidobacterium spp. was important for maintaining gut/intestinal barrier function, and they were found to be absent in the gut microbiota of mice fed a high-fat diet [P. gingivalis induces microbial dysbiosis by affecting the normal function of the complement system [P. gingivalis activated Notch-1 signaling in oral epithelial cells to promote the expression of PLA2-IIA that was associated with oral dysbiosis [Microbiota dysbiosis, an imbalance in the composition and function of the microbiome, has a prominent impact on the initiation and progression of many systemic diseases, such as immunological disorders, cardiovascular diseases, diabetes, and respiratory diseases . Dysbioses ratio . Moreovefat diet . Comparefat diet . Furtherfat diet . High-sufat diet . Intake fat diet –44. Excefat diet . In addifat diet . The numfat diet . Upon tifat diet . Moreovet system . The P. ysbiosis .Fig. 2MuP.gingivalis lipopolysaccharide-stimulated B cells was inhibited by miR-146a [Capnocytophaga) has been found in patients with loss of STAT3 function [To date, more than 80 autoimmune diseases has been identified, affecting a wide range of human body parts . A healtmiR-146a . In addimiR-146a , 58. Dysfunction . Oral mifunction . Autoimmfunction . Polymorfunction , 63. Impfunction . These ifunction . In addifunction , 67. Colfunction .Under harmonious host-microbial relationships, the microbiota provides vitamins, protects mucosal immunity and prevents colonization by pathogenic microorganisms, while the host offers an ecological niche and survival substances for the microbiota. Under dysbiosis, the mutually beneficial relationship between the host and microbes is disrupted, leaving the host more vulnerable to attacks by exogenous and endogenous pathogenic microorganisms. The host immune system in turn triggers a series of immune response processes, which might further aggravate microbiota dysbiosis.P. gingivalis inhibited the host-protective TLR2-MyD88 pathway by proteasomal degradation of MyD88 and concurrently activated the host-detrimental TLR2-Mal-PI3K pathway, which destroyed immune function by blocking cellular phagocytosis [Toll-like receptors (TLRs), which are germline-encoded pattern recognition receptors (PRRs), recognize pathogenic microorganisms and activate host signaling pathways to induce the production of cytokines and other inflammatory mediators . In addiocytosis .Accumulating evidence has demonstrated that microbiota dysbiosis is the critical factor for engendering autoimmune diseases . For insCampylobacter species were detected in the intestinal tissues and stool samples [The oral cavity is exposed to the external environment and anatomically connected with the gastrointestinal tract. Thus, oral bacteria escaping the inhibition of stomach acid can spread through the gastrointestinal tract and are closely correlated with various systemic diseases, such as IBD and RA , 81. Zha samples . A signi samples . Thus, tP. gingivalis significantly altered the gut microbiota in the mice. At the phylum level, Deferribacteres was increased and Bacteroidetes was decreased. Increased Deferribacteriaceae, Gemellaceae, and Clostridiaceae and decreased Paraprevotellaceae and Mogibacteriaceae were observed at the family level. Increased Coriobacteriaceae, Gemellaceae, and Clostridiaceae and decreased Prevotellaceae, Mogibacteriaceae, Dorea, Butyricicoccus, and Bilophila were found at the genus level [P. gingivalis, with elevated levels of phylum Bacteroidetes and serum endotoxin and a decreased level of phylum Firmicutes [Porphyromonadaceae and Fusobacterium. In addition, the levels of pro-inflammatory cytokines and chemokines such as IL-1β, IL-6 and colony-stimulating factor 1 were elevated, while the expression of anti-inflammatory cytokines such as IL-10 were decreased in colon tissue [P. gingivalis, followed by aggravation of collagen-induced arthritis [P. gingivalis promotes the production of RA-related cytokines and activation of monocytes through TLR pathways [P. gingivalis [Administration of us level . The comrmicutes . It was rmicutes . The endrmicutes . Intestirmicutes . Oxidatirmicutes . Gut barrmicutes . Also, irmicutes . Thus, tn tissue . Apart frthritis . P. gingpathways . Intestingivalis . The levngivalis . Thus, ongivalis .Streptococcus mutans and colitis. The results demonstrated that S. mutans may increase the severity of colitis, as it promoted the secretion of IFN-γ when entering the bloodstream [Fusobacterium nucleatum colonized tumor tissues [P. gingivalis, more severe cartilage destruction and higher expression of IL-17 in joints were found in mice orally treated with a mixture of P. gingivalis, T. denticola, and Tannerella forsythia [The main possible pathways by which oral pathogenic bacteria reach distant tissues and organs to trigger autoimmune diseases are the hematogenous and enteral routes. Invasive oral treatments, oral mucosal ulcers, injuries, and periodontitis provide convenient entry points for oral pathogenic microorganisms to invade the circulatory system. Subsequently, the oral bacteria and their soluble bacterial products can reach distant organs via the bloodstream , 96. Forodstream . In addi tissues . In addi tissues . Due to orsythia .P. gingivalis, have the ability to withstand stomach acidity and colonize the intestine [P. gingivalis [Klebsiella strains, as oral-derived intestinal pathogenic bacteria, possess the ability to resist a variety of antibiotics, including ampicillin (Amp) and tylosin (Tyl). For instance, compared with antibiotic-naïve mice, mice treated with Amp or Ty1 had a perturbed gut microbial profile, which was beneficial for colonization by Kp-2H7. Klebsiella strains strongly induce the accumulation of intestinal TH1 cells, leading to exacerbation of inflammatory diseases through abnormal activation of the intestinal immune system [Campylobacter concisus, THP-1 cells promoted the release of cytokines  and consequently increased the permeability of the intestinal epithelium [Klebsiella and Enterobacter derived from ligature-induced periodontitis and DSS-treated mice stimulated inflammasome production in colonic mononuclear phagocytes, followed by increased inflammation in the colonic mucosa. Additionally, Klebsiella and Enterobacter activated oral pathobiont-reactive Th17 cells, which had a tendency to migrate toward the inflamed gut [In addition to the hematogenous route, the enteral route is a major route for oral bacterial dissemination. Increased intestinal permeability is associated with the pathogenesis of many autoimmune diseases, such as type I diabetes, multiple sclerosis (MS), and SLE . An enorntestine . The gutngivalis . Generale system . To inveithelium . Oral paamed gut . Thus, cP.gingivalis and Aa) express the GroEL-like protein, which is a form of HSP60 family [Streptococcal M protein exhibits structural similarities with cardiac myosin, which underlies a potential pathogenic mechanism of chronic rheumatic heart disease [P. denticola and Bacillus cereus have a high degree of similarity with the self-autoantigen Ro 60KDa, which is often detected in SLE and Sjögren’s syndrome (SS). In addition, P. gingivalis, Streptococcus spp., and F. nucleatum have similar epitopes as the self-autoantigen pyruvate dehydrogenase complex E2 (PDC-E2), which is the possible mechanism underlying the initiation and progression of primary biliary cirrhosis (PBC) [“Molecular mimicry” was coined by R.Damian in 1964. It is demonstrated that more than 30 viral proteomes, especially the proteomes of human T-lymphotropic virus 1, Rubella virus, and hepatitis C virus, have a substantial pentapeptide overlap with the human proteome . These o0 family , 109. Of0 family . It was  disease . Increas disease . For insis (PBC) .Borrelia burgdorferi [P. gingivalis effectively cleave fibrinogen, fibronectin and type I collagen, which may promote the production of autoantibodies [P. gingivalis gives rise to the production of bacterial PADs, which catalyzes the citrullination of proteins [Aa produces pore-forming toxin LtxA to induce neutrophil hypercitrullination in patients with chronic periodontitis, and citrullinated autoantigens are the main immune targets in RA [Cytokines regulate some proteolytic enzymes to hydrolyze extracellular proteins, generating remnant epitopes. The remnant epitopes serve as autoantigens . Immune gdorferi . Of notetibodies . In addiproteins . Proteinproteins , 121. Futs in RA .P. gingivalis promotes the production of RA-related cytokines and monocyte activation through TLR pathways. Similarly, F. nucleatum enhances the expression of TNF-α, IFN-gamma, IL-1β, IL-6, and IL-17, which further exacerbates IBD [C. concisus promotes the secretion of proinflammatory cytokines from THP-1 cells, such as TNF-α, IL-1β, and IL-6, which increase the antigen permeability of the colonic epithelial barrier [A large body of evidence has revealed that cytokines are actively involved in the initiation and progression of autoimmune diseases . Thus, tates IBD . In addi barrier . It shou barrier . IL-1β s barrier . Amplifi barrier . The majUlcerative colitis (UC) and Crohn's disease (CD) represent two common types of IBD with chronic and recurrent characteristics . GeneticSaccharibacteria (TM7), Absconditabacteria (SR1), Leptotrichia, Prevotella, Bulleidia, and Atopobium was found in saliva specimens from patients with IBD [Streptococcus and Enterobacteriaceae species were enriched, while Lachnospiraceae and Prevotella were depleted, in saliva samples from patients with UC. Veillonellaceae was abundant, while significant depletion of Neisseriaceae and Haemophilus were observed, in saliva samples from patients with CD [Prevotella in the above two studies. The salivary microbiota profile of CD patients with periodontitis was significantly different from that of those with periodontitis alone and healthy individuals, characterized by an increase in the abundance of Proteobacteria and Firmicutes [Proteobacteria often leads to an imbalanced gut microbiota [g.Prevotella, f.Prevotellaceae, and p.Bacteroidetes, were more abundant in saliva samples from patients with active CD than in samples from control subjects or those in the remission phase [Streptococcus salivarius was consistently detected in saliva and fecal samples from patients with CD by whole-genome shotgun sequencing, which provides compelling evidence for the occurrence of ectopic gut colonization [Campylobacter species detected in the intestinal tissues and stool samples from patients with IBD were human oral Campylobacter species [ C. concisus, is significantly higher in colonic biopsy samples of UC patients than in control samples [C. concisus is rarely observed in healthy intestines [C. concisus in the intestine manifests as destruction of the colonic epithelial barrier, which results in the enhancement of antigen permeability and further facilitates the damage caused by other enteric bacterial species [Recently, there has been growing evidence that dysbiosis of the oral microbiome plays a key role in triggering and exacerbating IBDs. A significant increase in the abundance of with IBD . Strepto with CD . Differermicutes . It is wcrobiota . In addion phase . Streptonization , 139. It species . The det samples . In genetestines . The pat species , 142.Klebsiella strains isolated from the salivary microbiota with multidrug resistance were capable of colonizing the colon and increasing the numbers of proinflammatory TH1 cells, which subsequently aggravated the progression of IBD [P. gingivalis, promotes the production of Th17 cells and IL-17, causing aggravation of UC [P. gingivalis dramatically increases the severity of colitis by breaking down TJPs to increase the permeability of the intestinal epithelium [F. nucleatum is one of the resident bacteria and opportunistic pathogens in the human oral cavity [F. nucleatum [F. nucleatum exacerbated UC by promoting intestinal epithelial cell autophagy. In addition, F. nucleatum activates both the endoplasmic reticulum stress and IL-17F/NF-kappaB pathways, leading to the destruction of the intestinal mucosal barrier [F. nucleatum regulates proinflammatory M1 macrophages via the AKT2 signaling pathway to exacerbate UC [Mechanistically, the salivary microbiota from patients with periodontitis not only significantly changes the structure of gut microbes but also exacerbates colitis by reducing the level of unsaturated fatty acids and enhancing arachidonic acid metabolism . Klebsien of IBD . In addion of UC . It has ithelium . F. nucll cavity , 147. Itl cavity . More seucleatum . Su et a barrier , 150. Morbate UC .RA is a chronic autoimmune disease with a complex multifactorial etiology. The typical clinical manifestations of RA are symmetrical inflammation and pain in the small joints of the hands and feet. The concordance rate of RA in twins is extremely low, indicating the significance of environmental risk factors for the initiation and development of RA .P. gingivalis is closely correlated with the occurrence and development of RA, and the detailed molecular mechanisms of P. gingivalis for triggering and promoting autoimmune diseases have been summarized in Fig. P. gingivalis was significantly higher in tongue biofilms from non-remission RA patients than in those from remission patients [P. gingivalis was significantly increased in individuals positive for anti-cyclic citrullinated peptide compared with controls [P. gingivalis triggered the initiation of periodontitis and joint inflammation in rats [P. gingivalis developed more severe synovial inflammation and bone destruction in joints [P. gingivalis suffered from more severe arthritis. Interestingly, P. gingivalis affects the progression of RA by directly migrating into joints and inducing the secretion of ACPAs. The fimbriae function of P. gingivalis and the assistance of dendritic cells, macrophages, and neutrophils might contribute to its migration. collagen-induced arthritis mice injected with anti-FimA antibody had less severe arthritis, as anti-FimA antibody inhibited the attachment and aggregation of P. gingivalis [P. gingivalis IgG levels was observed in patients with PD after periodontal treatment. However, inflammation and the level of ACPAs changed little in the joint due to ectopic colonization by P. gingivalis [streptococcal species. Moentadj et al. found that Streptococcus species were abundant in the oral cavity of RA patients. Following the administration of streptococcal cell walls (SCWs) from Streptococcus. parasalivarius strains, ZAP-70-mutant SKG mice developed chronic arthritis [Treponema was greatly enriched in the PD and RA groups compared with the healthy controls by analyzing subgingival plaques [Prevotella and Veillonella in saliva samples [Streptococcus parasanguinis and Actinomyces meyeri were higher in subgingival plaque samples of RA patients than in non-RA individuals [It has been demonstrated that patients . The expcontrols . P. ging in rats . In addin joints . Similarngivalis . A reducngivalis . The devrthritis . A case‒ plaques . In addi samples . Moreoveividuals . The curSLE is a type of chronic autoimmune connective-tissue disease of unknown etiology that affects multiple organs and leads to tissue damage and extensive inflammation. SLE is more common in women, with a global widespread prevalence of 0.02–0.24% . NotablyT. denticola and T. forsythia were increased in SLE-active periodontal sites compared with SLE-inactive sites and sites in healthy controls [Veillonella, Streptococcus, and Prevotella were the predominant bacteria detected in saliva samples [Sphingomonadaceae, Halomonadaceae, and Xanthomonadaceae were dramatically decreased in SLE patients [Recently, a growing body of evidence has indicated the close correlation between the oral microbiota and SLE , 166. Pecontrols . The mic samples . Howeverpatients . The incBacteroides was negatively linked to SLE disease activity, indicating that manipulating the composition of the oral microbiota might be an effective strategy for treating SLE [Notably, periodontitis might activate immune responses by maintaining high expression of TLR2 and TLR4, resulting in aggravation of the occurrence and progression of SLE. Potential cross-recognition was observed between human self Ro60 and homologous peptides from the oral microbiota, which illustrated the potential ability of bacterial antigens to induce an autoimmune response . The expting SLE .Actinobacteria and Firmicutes, including Streptococcus spp., Actinomyces spp. and Rothia spp were the predominant bacteria detected in oral swabs of T1D patients [Streptococcus was increased in the unstimulated saliva samples from T1D patients by using 16S rRNA sequencing [Aggregatibacter was found only in patients with T1D, while it was absent in the healthy controls and patients with periodontal diseases [Capnocytophaga sputigena and C. ochracea were the more common detected bacterial in subgingival samples from patients with T1D [T1D is a T-cell mediated autoimmune disease characterized by insulin deficiency due to the destruction of pancreatic β-cells. T1D is the most common type of diabetes in children and adolescence . Accumulpatients . In addiquencing . Aggregadiseases . Capnocywith T1D . Noteworwith T1D , 184. Imwith T1D .Alistipes and Faecalibacterium prausnitzii) contributed to maintain the function of the mucous barrier, microvilli adhesion, and exocrine pancreas were depleted in new-onset T1D [Bifidobacterium, Peptostreptococcus, Atopobium, Mannheimia, Campylobacter, Olsenella, Lactobacillus, and Acidpropionibacterium were abundant in periodontitis-associated microbiota-administered (PAO) mice, while Cutibacterium, Streptococcus, Actinomyces, Faecalibaculum, Granulicatella, Gemella, Alloprevotella, and Staphylococcus were enriched in HAO mice [Bacteroides and Staphylococcus and reduced level of Lactobacillus spp may result in a decrease in Th17 cells and an increase in the M1/M2 macrophage ratio [Bacteroides fragilis (BF) tends to aggravate T1D under the condition of increased gut permeability [P. gingivalis or F. nucleatum that increase the intestinal mucosa permeability, BF-like gut microorganisms promote the progression of T1D [Microbial communities residing in oral and intestinal niches may synergistically promote the progression of T1D, highlighting the important role of oral-gut microbiota axis. Metaproteomics revealed that the microbial taxa  . AIH, a patients . Howeverpatients . In addie levels .autochthonous families and an increased abundance of Enterobacteriaceae and Enterococcaceae were observed in the saliva samples from cirrhotic patients [Eubacterium and Veillonella were increased in saliva samples from PBC patients, while that of Fusobacterium was decreased [Bacteroidetes, Campylobacter, Prevotella, and Veillonella were found to be enriched in the saliva samples of PBC patients, while Enterococcaceae, Granulicatella, Rothia, and Streptococcus were depleted. In addition, saliva supernatants from PBC patients induced the production of inflammatory mediators, and the levels of inflammatory cytokines were significantly decreased following effective tooth brushing, indicating that a dysregulated oral microbiota may stimulate inflammatory responses to promote the development of PBC [Streptococcaceae were found to be significantly increased in small intestinal lining in cirrhotic mice [PBC is a chronic cholestatic liver disease that occurs predominant in women and is characterized by damage to small intrahepatic bile ducts. PBC may be driven by microbial imbalance, which leads to liver inflammation towards fibrosis and subsequent cirrhosis. A decreased abundance of patients . Furtherecreased . By usint of PBC . Of notetic mice . Due to tic mice . The immtic mice . Moreovetic mice . The bactic mice .Veillonella, Scardovia, and Streptococcus were greatly enriched, while native bacteria were depleted, in the saliva samples from PSC patients by using 16S rRNA sequencing [Rothia and Haemophilus were less abundant in saliva samples from PSC patients than in healthy controls [PSC is a rare chronic cholestatic disease characterized by progressive inflammation and fibrosis of the intrahepatic and extrahepatic bile ducts. PSC might develop into cirrhosis, portal hypertension, and liver decompensation in the advanced stages . Recentlquencing . Furthercontrols . By usincontrols . Notablycontrols . It was controls . Due to IgAN is an immune-mediated and idiopathic glomerulonephritis characterized by mesangial hyperplasia with IgA deposition. The long-term prognosis for IgAN remains poor, with approximately 30–40% of IgAN patients developing end-stage renal failure within 10–20 years , 232. ToGranulicatella abundance and a marked reduction in Prevotella and Veillonella abundance were found in the saliva samples of IgAN patients [Firmicutes to Proteobacteria was significantly reduced, while the Pasteurellaceae family was found to be enriched, in saliva samples of IgAN patients [Neisseria was significantly higher in saliva samples from the IgAN group [Capnocytophaga, Rothia, and Haemophilus in saliva samples. In particular, the abundance of Capnocytophaga was found to be positively correlated with the level of proteinuria [Proteobacteria and Actinobacteria at the phylum level, Betaproteobacteria, Bacilli, Actinobacteria, Flavobacteriia, and Gammaproteobacteria at the class level, and Bergeyella, Capnocytophaga, Actinomyces, Corynebacterium, Comamonas, Lautropia, and Streptococcus at the genus level were significantly abundant in the subgingival microbiome from CP patients with IgAN compared to those without IgAN. In addition, the bacterial composition in subgingival plaque differed greatly between CP patients with and without IgAN [Accumulating evidence has demonstrated that the oral microbiome might be actively involved in the pathogenesis of IgAN. By using high-throughput sequencing technology, a dramatic increase in patients . Piccolopatients . CompareAN group . In additeinuria . The chaout IgAN .S. mutans might be involved in the incidence and progression of IgAN [S. mutans was significantly abundant in saliva samples of IgAN patients. In addition, a higher Cnm protein-positive rate in tonsil specimens was observed in patients with IgAN [S. mutans [S. mutans might promote the deposition of IgA1 in mesangial areas in glomeruli by abnormal glycosylation of serine or threonine amino acids of IgA1 [In particular, Cnm- ( +)  of IgAN . First, ith IgAN . Recentl. mutans . More im of IgA1 . The detS. mutans and Streptococcus. gordonii [Due to the indispensable role of oral microbiota dysbiosis in the initiation and progression of autoimmune diseases, targeting the oral microbiota might be an effective strategy for preventing and treating autoimmune diseases Fig. . Maintengordonii . Interesgordonii . TargetiFecal microbiota transplantation (FMT) is an emerging strategy for the treatment of refractory diseases in recent years. For example, this approach has demonstrated promising effects in maintaining remission status in CD and inducing remission in UC , 248. InEnhancing the synergistic effects of balancing the oral microbiota might be important for achieving better therapeutic outcomes. TNF-α siRNA nanomedicine-targeted macrophages significantly attenuated TNF-α levels and improved IBD in an animal model , 253. FuIt is now well recognized that oral microbiota dysbiosis plays a crucial role in modulating the initiation and development of many autoimmune diseases, and targeting oral microbes might be a promising strategy for ultimately achieving the goal of curing autoimmune diseases. Unfortunately, few clinical trials have evaluated the beneficial effects of microbiota-based therapies on autoimmune diseases. In addition, effective strategies for balancing the oral microbiota to treat autoimmune diseases are urgently needed. Moreover, the underlying molecular mechanisms by which host-microbe interactions in the oral cavity remotely trigger and exacerbate autoimmune diseases remain unclear. Systematic combination of metabolomics, metagenomics, metatranscriptomics, and proteomics might improve our understanding of the complex interactions between the oral microbial ecosystem and immune system, which might provide novel oral microbiota targets for treating autoimmune diseases.


Salmonella pathogenicity island 2 (SPI-2)-encoded type III secretion system (injectisome) is assembled following uptake of bacteria into vacuoles in mammalian cells. The injectisome translocates virulence proteins (effectors) into infected cells. Numerous studies have established the requirement for a functional SPI-2 injectisome for growth of Salmonella Typhimurium in mouse macrophages, but the results of similar studies involving Salmonella Typhi and human-derived macrophages are not consistent. It is important to clarify the functions of the S. Typhi SPI-2 injectisome, not least because an inactivated SPI-2 injectisome forms the basis for live attenuated S. Typhi vaccines that have undergone extensive trials in humans. Intracellular expression of injectisome genes and effector delivery take longer in the S. Typhi/human macrophage model than for S. Typhimurium and we propose that this could explain the conflicting results. Furthermore, strains of both S. Typhimurium and S. Typhi contain intact genes for several ‘core’ effectors. In S. Typhimurium these cooperate to regulate the vacuole membrane and contribute to intracellular bacterial replication; similar functions are therefore likely in S. Typhi.The  Salmonella enterica are intracellular bacterial pathogens that cause different diseases among many different mammalian hosts. The broad-host-range serovar Typhimurium usually causes self-limiting gastroenteritis in otherwise healthy humans but can spread to cause invasive non-typhoidal Salmonella disease among individuals with impaired immunity. Serovars Typhi and Paratyphi are the causes of the systemic disease typhoid fever. Infection of certain mouse strains with Salmonella Typhimurium leads to substantial bacterial colonization and replication in macrophages in the liver and spleen [Salmonella Typhi and non-typhoidal serovars, including the Typhi-specific capsule [Serovars of d spleen . Althougd spleen  and viru capsule  and its  capsule .S. enterica is the Salmonella pathogenicity island 2 (SPI-2)-encoded type III secretion system (hereafter referred to as the SPI-2 injectisome), which is assembled following uptake of bacteria into Salmonella-containing vacuoles (SCVs) in mammalian cells. The injectisome comprises a needle-like structure on the surface of the bacterial cell and translocon proteins that are secreted through the needle then insert into the vacuole membrane to form a pore. This provides a conduit for the translocation of up to 30 different virulence proteins (effectors) into infected cells, including epithelial cells, macrophages, dendritic cells and other cell types. Almost all sequenced strains of serovars of S. enterica carry intact copies of the 28 genes involved in the assembly and function of the SPI-2 needle and translocon [A major virulence system of anslocon , as wellanslocon .S. Typhimurium [S. Typhi are not consistent. Some have shown that it is required for replication in human epithelial cells [S. Typhi SPI-2 injectisome. If its functions differ substantially from those of S. Typhimurium, then we need to understand the differences and their underlying mechanisms. An inactivated SPI-2 injectisome forms the basis for live attenuated S. Typhi vaccines that have undergone extensive trials in humans [S. Typhimurium SPI-2 injectisome, this would highlight further distinctions between the mouse infection model with S. Typhimurium and typhoid fever in humans.Various mutations that inactivate the SPI-2 injectisome (generating SPI-2 null mutant strains) have been used to assess its overall contribution to intracellular growth and virulence. Whereas numerous studies have established the requirement for a functional injectisome to enable intracellular growth of himurium , the resal cells  and in hal cells . Howeveral cells . It is in humans . Therefoet al. [S. Typhi in human-derived THP1 macrophages and reported no differences between these strains. However, while numbers of wild-type and SPI-2 mutant c.f.u. recovered from infected macrophages were similar at various time points up to 24 h post-uptake, at 48, 72 and 96 h post-uptake, consistently fewer SPI-2 mutant c.f.u. were recovered [Experiments using SPI-2 null mutants to assess the contribution of the injectisome to intracellular survival and growth in host cells lines have relied mainly on counting the number of intracellular colony-forming units (c.f.u.) of bacteria recovered at different times post-uptake. Forest et al. , examineecovered . The difecovered , but perS. Typhi with serial 24 h passages of mutants through THP-1 macrophages, followed by comparison of input and output ratios with a fourfold change threshold as cut off. This led to the identification of 130 attenuated mutants, including 3 carrying mutations in ssaN, ssaP and ssaQ, which were significantly underrepresented in the output pools . In S. function . HoweverP mutant . The autet al. [S. Typhi in human-derived epithelial cells and U937 macrophages. In epithelial cells, loss of injectisome function caused an approximately eightfold reduction (c.f.u.) and fourfold reduction (flow cytometry) in intracellular proliferation. However, very little growth of either wild-type or SPI-2 mutant S. Typhi occurred in U937 macrophages at 24 h post-uptake [In a third study, Reuter et al. , used bot-uptake , making et al. [aroC double-mutant strain and compared it with an aroC single mutant, both in the presence and absence of additional aromatic compounds (to complement the aroC mutation). They showed that in both cases, the SPI-2 null mutation reduced the growth of S. Typhi within these cells. In follow-up work, Stratford et al. [et al. [In contrast to the work described above, two papers have reported an effect of a SPI-2 injectisome null mutation on intracellular growth in U937 macrophages at 48 h post-uptake. Khan et al.  used a Sd et al.  used the [et al.  measuredS. Typhi virulence have exploited mice engrafted with human haematopoietic stem cells (hu-SRC-SCID). Unlike non-engrafted mice, these animals support the growth of S. Typhi and were used to screen transposon mutant libraries for in vivo growth defects [Salmonella, as well as a direct measurement of SPI-2-dependent growth in THP-1 macrophages. These tests also failed to show any attenuation for the SPI-2 mutant over a 24 h infection period [et al. but involving a lower dose of mixed inoculum and a 5 day infection period, fewer SPI-2 mutants than wild-type bacteria were recovered from spleens (but not livers) of mice [Other tests for the involvement of SPI-2 in  defects . While nn period . However of mice .S. Typhi infection is based on immunodeficient Rag2−/−γc−/− mice engrafted with human foetal liver haematopoietic stem and progenitor cells [S. Typhi, which can be detected in haematopoietic cells in the spleen and a more persistent infection is established, allowing analysis up to 4 weeks post-inoculation. Therefore, it would be very interesting to examine SPI-2-dependent infection dynamics in these mice.A different mouse model for or cells . These met al. paper [S. Typhimurium bacteria expressing the SPI-2 ssaG promoter was over 90 % at 8 h post-uptake, while for S. Typhi the percentage rose steadily from approximately 50 % at 8 h to 77 % at 24 h post-uptake. Similarly, expression from S. Typhi of a fluorescent reporter, derived from a fusion to the promoter of the SPI-2 injectisome effector gene sifA, was delayed at 8 and 16 h post-uptake in epithelial cells compared to S. Typhimurium, but reached similar levels of induction by 24 h [S. Typhi/human macrophage model than for S. Typhimurium, and in keeping with the results of Khan et al. [et al. [What can explain the apparently conflicting results from these studies? The Reuter l. paper  also inc by 24 h . Therefon et al. , and StrS. Typhi induce cytotoxicity has not been investigated, but many S. Typhi strains encode the effector SseL [S. Typhimurium-infected mouse macrophages [S. Typhi with a functional SPI-2 injectisome.It should also be kept in mind that when using approaches based on c.f.u. counts or flow cytometry of constitutively fluorescent bacteria, any difference in macrophage cytotoxicity caused by wild-type or mutant bacteria has the potential to yield an underestimation of the true level of intracellular bacterial replication for one of the strains. Whether SPI-2 injectisome effectors of tor SseL , which hrophages . TherefoS. Typhimurium effector gene repertoire is absent among sequenced strains of S. Typhi  inhibition of innate immune signalling pathways, (2) suppression of T cell responses and (3) bacterial survival and replication within host cells . This laudogenes , it is nS. Typhi . While tS. Typhimurium, sseF, sseG, steA and sifA single mutants are all attenuated for growth in mouse macrophages [trans-Golgi network-derived pathway. This could provide membrane for expanding SCVs and/or nutrients for bacterial growth [S. Typhimurium or S. Typhi and have been implicated in intracellular S. Typhimurium nutrient acquisition [S. Typhimurium is unstable [Salmonella.In rophages . SseF anrophages . In epitl growth . Translol growth . It prevl growth  and is ruisition . In macruisition . Withoutunstable  and its unstable  and SopDunstable . SteA isunstable . PipB2 aunstable . Collectet al. found only low levels of cytosolic sifA mutant S. Typhi, concluding that this might reflect lower levels of proliferation and lower dependence on SifA function to maintain the integrity of the expanding SCV [sseJ and sopD2 are frequently pseudogenes in S. Typhi [S. Typhi strain used by Reuter et al. [sifA mutant S. Typhi. Regardless, Hamblin et al. [S. Typhi pipB2 and sifA mutants at 24 h post-uptake, indicating that the encoded proteins contribute to replication of S. Typhi in human THP-1 macrophages.Reuter ding SCV . HoweverS. Typhi  and if nr et al. , an alten et al.  detectedS. Typhi, most strains contain intact genes for pipB, sseL and sifB, whose functions are poorly understood. Their apparent functionality suggests that they are under selection and carry out important physiological activities. Clearly, further study of these effectors is needed to improve our understanding of the intracellular biology of S. enterica in general. Strikingly, most S. Typhi strains lack several effectors  that in S. Typhimurium interfere with innate immune signalling pathways [S. Typhi of the polysaccharide Vi capsule, which is linked to a lack of intestinal inflammation by interfering with access of pathogen-associated molecular patterns (PAMPs) to pattern recognition molecules, resulting in less proinflammatory cytokine production [S. Typhi contain an intact copy of a gene encoding the SPI-2 injectisome effector SteD [S. Typhimurium SteD suppresses the activation of T cell responses [Salmonella in humans [With respect to other SPI-2 injectisome effectors in pathways . It is poduction . Sequenctor SteD ; in S. Tesponses , which an humans .S. Typhi SPI-2 effector function is epithelial cells [S. Typhi in deeper tissues [S. Typhi SPI-2 injectisome in intramacrophage growth, and we suggest that more studies need to be done, involving a detailed analysis of the secretion kinetics of individual effectors of the two serovars, more extended periods of infection than those used in the majority of experiments to date and using more sensitive assays for bacterial replication than bulk c.f.u. counts.It remains possible that the main host cell type for al cells , but sin tissues , it seem


Talaromyces purpureogenus strains isolated from bee bread against Paenibacillus alvei (associated with European foulbrood disease) and three Aspergillus species that cause stonebrood disease. We found that methanol extracts of T. purpureogenus strains B18 and B195 inhibited the growth of P. alvei at a concentration of 0.39 mg/mL. Bioactivity-guided dereplication revealed that the activity of the crude extracts correlated with the presence of diketopiperazines, a siderophore, and three unknown compounds. We propose that non-pathogenic fungi such as Talaromyces spp. and their metabolites in bee bread could be an important requirement to prevent disease. Agricultural practices involving the use of fungicides can disrupt the fungal community and thus negatively affect the health of bee colonies.Honey bees coexist with fungi that colonize hive surfaces and pollen. Some of these fungi are opportunistic pathogens, but many are beneficial species that produce antimicrobial compounds for pollen conservation and the regulation of pathogen populations. In this study, we tested the in vitro antimicrobial activity of  Apis mellifera, Linné 1758) (Hymenoptera: Apidae) play a key role in agroecosystems by augmenting wild pollinators and thus ensuring crop quality and yield stability. However, an array of biotic and abiotic stressors associated with agricultural intensification, parasites, and pathogens negatively affect the health of managed bees ⁺ and m/z 211.1438 [M+H]⁺, corresponding to the molecular formulae C14H16N2O2 and C11H18N2O2, respectively. The compounds were identified as the diketopiperazines cyclo-Phenyl- alanyl-Prolyl and cyclo-Leucyl-Prolyl  also retrieved no hits. The identity of the compound remains unknown. An isomer of the same compound was identified in fractions 33–34. In addition, these fractions contained 5,6,8-trihydroxy-3-methyl-2-benzopyran-1-one  -, trimol. ester, -(9CI)  (m/z 516.2204 [M+H]+) could not be dereplicated. Ultimately, fraction 114 contained one major ion (m/z 281.2482 [M+H]⁺) and a minor ion (m/z 379.3368 [M+H]⁺). Neither compound aligned with any reference compound spectrum. The predicted molecular formula search of the major ion (C18H32O2) retrieved >100 candidates in the DNP, including ubiquitous linolenic acid. However, the nonspecific fragmentation did not allow structural assignment.The B18 extract yielded five zones of consecutive fractions that inhibited the growth of the test strain, namely fractions 26–28, 30–31, 33–34, 39, and 114 . The fral-Prolyl : 1–2. Frl-Prolyl : 1 as weH2O+H]⁺) : 3. Frac [M+H]⁺) : 4. A seTalaromyces recently found in honey bee bread and tested the antimicrobial activity of methanol extracts against bacteria associated with EFB  and opportunistic pathogens of the genus Aspergillus.The role of non-pathogenic fungi as regulators of pathogens in the hive and in bee bread has been addressed in several studies ,33,34. IT. purpureogenus , formerly known as Penicillium purpureogenum . Talaromyces species have previously been recovered from A. mellifera honey [A. cerana bee bread [A. dorsata  [Melipona spp.) [T. purpureogenus had not been identified in honey bees before, although it has been found in Coleoptera (bark beetles), Diptera (mosquitoes), Hymenoptera (ants), Hemiptera, and Trichoptera [Based on morphology, DNA barcoding, and phylogenetic analysis, we assigned all seven strains to the species ra honey , A. ceraee bread , dead ads, 1793) , and stina spp.) . Howeverchoptera .Talaromyces in bee bread, its presence is not surprising because this ubiquitous genus can be collected by bees from various sources [Talaromyces strains from some of the hives in one rural location, an urban area, and the city periphery. Seasonal factors may be relevant because we found the Talaromyces strains only in spring. Other studies exploring the composition of fungi in bee bread in Europe did not find any Talaromyces species, but samples were collected in the summer [Talaromyces is consistent with our results. In worker bees, the prevalence of fungi was higher in fall and winter [Although few studies have reported the presence of  sources . Bees pa sources ,83. Inte sources . We isole summer ,84, whend winter . The comTalaromyces species in apiaries located directly on agricultural land. The foraging distance of A. mellifera ranges from several hundred meters to several kilometers, depending on the available pasture [Talaromyces in bee bread. However, more research is needed to correlate the presence and seasonal prevalence of T. purpureogenus and other Talaromyces species in bee bread.We did not find any  pasture ,86. The  pasture  and cult pasture . Our resTalaromyces strains B18 and B195 showed antibacterial activity against the pathogen P. alvei and other tested strains of P. lautus and P. lactis. Bioactivity-guided dereplication in assays against P. lautus revealed multiple fractions and corresponding inhibitory compounds  that are also likely to show activity against the other Paenibacillus species. Siderophores are metal chelators that facilitate the uptake, intracellular transport, and storage of iron in plants, fungi, and bacteria, making them useful for both medical and environmental applications [Talaromyces [Our in vitro assays revealed that extracts of ications . Most fuications , such asaromyces . The bioaromyces . The abiaromyces . Severalaromyces  and lovaaromyces . Given tT. purpureogenus. Depending on the strain and cultivation conditions, T. purpureogenus isolated from the bee bread can affect colony health and pathogen resistance in different ways, such as the production of antimicrobial compounds as discussed here, as well as mycotoxins such as the rubratoxins found in our previous study [Talaromyces may consist of an assemblage of species/strains with various metabolic activities, as described for bee-related Aspergillus species [Penicillium and Alternaria [Most sequence-based studies identify fungi to the genus or species level. Our results highlight the metabolic diversity of different strains of the species us study . The gen species . These f species . Similarternaria ,95, are T. purpureogenus, can produce protective antimicrobial compounds as well as lethal mycotoxins. The strain-level balance is therefore important for the beneficial function of the mycobiome. Anthropogenic activity, such as the use of fungicides in agriculture, can disrupt this balance and negatively affect colony health.Fungi in bee bread play an important role in the regulation of pathogens, conferring resistance and promoting colony survival. Many bee bread fungi, including


Tamarix L. is of great ecological and economic significance in arid desert ecosystems. This study reports the complete chloroplast (cp) genomic sequences of T. arceuthoides Bunge and T. ramosissima Ledeb., which are currently unknown, by high-throughput sequencing. The cp genomes of T. arceuthoides 1852 and T. ramosissima 1829 were 156,198 and 156,172 bp in length, respectively, and contained a small single-copy region , a large single-copy region , and a pair of inverted repeat regions . The two cp genomes possessed 123 genes arranged in the same order, including 79 protein-coding, 36 tRNA, and eight rRNA genes. Of these, 11 protein-coding genes and seven tRNA genes contained at least one intron. The present study found that Tamarix and Myricaria are sister groups with the closest genetic relationship. The obtained knowledge could provide useful information for future phylogenetic, taxonomic, and evolutionary studies on Tamaricaceae. Tamarix L. contains approximately 100 species that are primarily distributed in the arid and semi-arid areas of continental Asia and North Africa, along with intermittent distribution along the west coast of South Africa and parts of Europe  have been published  genomes present an effective means of improving the rate of species identification and has been developed as a tool for plant phylogenetic studies at different taxonomic levels , and voucher specimens were deposited at the Specimen Museum of Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences  with collection number LWJ-W-4, LWJ-W-7 and identifier Xi. Y. Wang. All materials utilized in the present study are listed in Supplementary Table.Samples of Leaf samples were dried in silica gel and stored at −20 °C for DNA extraction, which was performed using a plant genome extraction kit (DP320) obtained from Tiangen Biochemical Technology  as per the manufacturer’s instructions. Extracted DNA was sequenced with 2 × 150 bp paired-end reads on the Illumina HiSeq X Ten platform at the Molecular Biology Experiment Center, Germplasm Bank of Wild Species in Southwest China.https://github.com/quxiaojian/PGA), prior to manual adjustments using Geneious version 9.1.7  as a reference. The sequence data of T. arceuthoides and T. ramosissima are publicly available in the GenBank (https://www.ncbi.nlm.nih.gov/) under accession numbers ON620259 and ON620260. Organellar Genome Draw (OGDRAW)  analyses were conducted using RAxML-HPC v. 8 . The evaluation of the most appropriate substitution models and the construction of the phylogenetic tree were both carried out on the CIPRES Science Gateway portal .The new cp genomic sequences were found to occupy a circular confirmation, 156,172 and 156,198 bp in length, respectively, comprising a small single-copy region  as well as a large single-copy region  that were separated by a pair of inverted repeat regions . Both the cp genomes possessed 123 genes that were arranged in the same order, including 79 protein-coding genes, 36 tRNA genes, and eight rRNA genes. Of these, 11 protein-coding and seven tRNA genes contained at least one intron . These tTamarix and Myricaria were sister groups (BS = 100%). Tamarix was divided into three main lineages, the new sequences T. arceuthoides and T. ramosissima clustered with T. karelinii together (The phylogenetic tree analysis revealed that together .T. arceuthoides and T. ramosissima. The structures obtained for the two cp genomes in this study are consistent with previous findings (Pang T. arceuthoides and T. ramosissima, indicating that the molecular identification of the genus Tamarix might require to select highly variable regions in cp genomes, or add additional nrDNA sequences.We report the cp genomes of ngs Pang . Our stuClick here for additional data file.Click here for additional data file.Click here for additional data file.Click here for additional data file.Click here for additional data file.Click here for additional data file.


Pericytes are microvascular mural cells that directly contact endothelial cells. They have long been recognized for their roles in vascular development and homeostasis, but more recently have been identified as key mediators of the host response to injury. In this context, pericytes possess a surprising degree of cellular plasticity, behaving dynamically when activated and potentially participating in a range of divergent host responses to injury. Although there has been much interest in the role of pericytes in fibrosis and tissue repair, their involvement in the initial inflammatory process has been understudied and is increasingly appreciated. Pericytes mediate inflammation through leukocyte trafficking and cytokine signaling, respond to pathogen-associated molecular patterns and tissue damage-associated molecular patterns, and may drive vascular inflammation during human SARS-CoV-2 infection. In this review, we highlight the inflammatory phenotype of activated pericytes during organ injury, with an emphasis on novel findings relevant to pulmonary pathophysiology. Pericytes are integral to the microvascular unit during development and in homeostasis . PericytOriginally described in human lung capillaries by Weibel  in 1974,In the healthy state, the microvascular unit is characterized by a state of quiescence. Endothelial cells form tight junctions with adjacent endothelial cells, express low levels of inflammatory markers and leukocyte adhesion molecules, exhibit anticoagulative properties, and in the lung, high nitric oxide synthesis to maintain vasodilation . SignaliWith injury, the microvasculature becomes “activated” with a series of physiological events: inflammatory cell recruitment, vascular leakage, coagulopathy, and disruption to nitric oxide synthesis or responsiveness. Investigation of these events has traditionally focused on the role of endothelial cells. In recent years, however, it has become increasingly recognized that the subendothelial layer of the microvascular unit, marked by pericytes and extracellular matrices, also plays crucial roles in inflammation and repair.Seminal studies of pericytes as progenitors of scar-forming cells in the skin, central nervous system (CNS), kidneys, and lungs positioned this stromal subtype as a dynamic population in fibrosis , 30–33. In this review, we focus on the mechanisms by which pericytes activate local inflammatory responses after lung injury. Work from our group, using transgenic models that label mouse lung pericytes, has demonstrated robust inflammatory responses in pericytes and attenuated lung inflammation when pericytes are selectively depleted –16, 34. An important component of the initial inflammatory response to tissue injury in the lung and other organs is recruitment of circulating leukocytes. In the alveolar compartment of the lung, leukocytes transmigrate across alveolar capillary walls following luminal interaction with endothelial adhesion molecules such as intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) . After cActivated pericytes induce adhesion molecule expression in endothelial cells , 39. TwoIn addition to leukocyte adhesion, pericytes also facilitate leukocyte trafficking through cytokine release. Like other stromal cells, pericytes are capable of sensing damage-associated and pathogen-associated molecular patterns . Pericytes in multiple organs express functional pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) and NOD-like receptors (NLRs). Human neurovascular pericytes, for instance, express TLR 2, 4, 5, 6, and 10 and NOD1, NOD 2, NLRPs 1–3, 5, 9, 10, and NLRX at the transcript level in vitro. Activation of select PRRs in cultured human neurovascular pericytes leads to inflammasome formation and secretion of inflammasome-cleaved pro-IL-1β . In respWork by our group and by our collaborators demonstrate a similar proinflammatory secretome in both murine and human lung pericytes . Pericyt+ monocytes to the lung during lung injury. We showed that conditioned media from activated pericytes enhance chemotactic migration of bone marrow-derived macrophages (BMDMs), which is reversed with CCR2 blockade (receptor for CCL2 and CCL7) using a small molecular antagonist . The 50 kDa full-length protein is secreted and cleaved into C-terminus and terminus products by furin and other proteases in the extracellular space . In cancby ELISA . Moreovenockdown . These fNos2 is significantly upregulated in activated lung pericytes and leads to increased nitrites (a stable breakdown product of nitric oxide) in conditioned media of activated lung pericytes. NOS2 is an inducible nitric oxide synthase that metabolizes l-arginine to nitric oxide. Nitric oxide is a well-recognized regulator of endothelial cell proliferation and microvascular tone  to transgenic mice with pericyte-restricted simian DT receptor (iDTR) expression . Direct day 3  and day 3  R03HL155075 and R01HL166273-01 (to C.F.H.) and Institutional KL2 training award 5KL2TR002317-04 (to S.G.R.).No conflicts of interest, financial or otherwise, are declared by the authors.S.G.R. and C.F.H. prepared figures; S.G.R. and C.F.H. drafted manuscript; S.G.R., C.F.H., W.C.L., and W.A.A. edited and revised manuscript; S.G.R., C.F.H., W.C.L., and W.A.A. approved final version of manuscript.


However, its efficacy in hospitalized patients has not been well-studied. We assessed the impact of LV-BP on time to colonoscopy, hospital LOS, and bowel preparation quality among inpatients.Delays in inpatient colonoscopy are commonly caused by inadequate bowel preparation and result in increased hospital length of stay (LOS) and healthcare costs. Low-volume bowel preparation . LV-BP was also significantly associated with decreased hospital LOS among older patients (age ≥ 75 years), patients with chronic kidney disease, and patients who were hospitalized with gastrointestinal bleeding.Among 1,807 inpatients included in this study, 293 and 1,514 patients received LV-BP and HV-BP, respectively. Among the propensity score-matched population, LV-BP was associated with a shorter time to colonoscopy  while having similar odds of adequate preparation (odds ratio: 1.02 [95% confidence interval: 0.71–1.46]; LV-BP is associated with decreased time to colonoscopy in hospitalized patients. Older inpatients, inpatients with chronic kidney disease, and inpatients with gastrointestinal bleeding may particularly benefit from LV-BP. Prospective studies are needed to further establish the role of LV-BP for inpatient colonoscopies. Adequate bowel cleansing is a critical component in the care of hospitalized patients undergoing diagnostic or therapeutic colonoscopy. Inadequate bowel preparation is associated with worse clinical outcomes, including increased rates of complications, missed pathologic lesions, repeated bowel preparation medication administration, and even aborted colonoscopy procedures –6. In tusodium sulfate, potassium sulfate, and magnesium sulfate (Suprep), have been found to increase preparation quality and tolerability in outpatients, representing an attractive alternative to the standard high-volume polyethylene glycol (PEG) preparations (Low-volume bowel preparations (LV-BPs), such as arations ,14. Howearations ,16. As sThe aim of this study was to evaluate the impact of LV-BP on time to colonoscopy, quality of bowel preparation, and hospital LOS in hospitalized patients as compared with a propensity score-matched (PSM) historical cohort who received traditional high-volume PEG-based preparation.This single-center, retrospective, observational study, performed at a quaternary academic medical center, compared the differences between low-volume and high-volume bowel preparations for inpatient colonoscopies. Hospitalized adult patients (18 years or older) from January 1, 2018, to January 31, 2021, undergoing colonoscopy at this center were included in this study. Patients who had ileus, toxic megacolon, evidence of gastrointestinal obstruction, an allergy to either bowel preparation, received bowel preparation for other reasons before their colonoscopy, or who were unable to give consent to the procedure were excluded from the analysis.The suitability of the patient for colonoscopy was determined by the inpatient gastroenterology consult team, consisting of fellows and an attending gastroenterologist. Patients received either traditional high-volume PEG-based bowel preparation  or low-volume bowel preparation containing sodium sulfate, potassium sulfate, and magnesium sulfate . LV-BP became available starting on June 16, 2020, and became the primary bowel preparation medication ordered by inpatient providers. HV-BP could still be used at the discretion of the consulting team based on underlying patient comorbidities . Both bowel preparations were administered using split-dose administration . If the colon preparation was still incomplete after this, an additional split dose was given to the patient.Colonoscopies were performed in the endoscopy unit at Massachusetts General Hospital. The Massachusetts General Hospital endoscopy unit has 1 procedure room dedicated each day for inpatient procedures alone and is also open for procedures on both weekend days. One anesthesiologist supervises the certified registered nurse anesthetist assigned to the inpatient endoscopy room. Procedures were performed under moderate sedation (midazolam and fentanyl) or deep sedation  at the discretion of the gastroenterologist and anesthesia providers.The fellow performed the colonoscopy under the direct supervision of an attending gastroenterologist. Procedure notes were documented in Provation, an endoscopy procedure documentation software, by the fellow and reviewed by the attending. All colonoscopies were performed using Olympus 190-series (CF-HQ190AL and PCF-H190L) colonoscopes. The success of cecal intubation was established by visualization of the appendiceal orifice and ileocecal valve.International Classification of Disease, 10th revision codes  . Additio2 tests for continuous, count/score, and binary variables, respectively. For continuous and count/score variables, the median and interquartile range  and mean and 95% confidence intervals (CIs) were also calculated, respectively.Characteristics and outcomes of patients in both bowel preparation groups were compared using Mann-Whitney U , Poissonhttp://links.lww.com/CTG/A789)  . The matTG/A789) . If the Using the PSM population, 3 multivariate regression models were developed to assess the association between LV-BP and each of the study outcomes. The multivariate regression models were used to reduce biases in the estimated treatment effect of LV-BP that stem from the nonexact balance of covariates after propensity score matching ,22. To ahttp://links.lww.com/CTG/A789).To improve model interpretability and reduce overfitting of the final regression models, minimum-maximum scaling of the feature values  and featInternational Classification of Disease, 10th revision or Medicare severity diagnosis-related group related to gastrointestinal bleeding and kidney disease, respectively. For each subpopulation, the propensity scores used for 1:2 matching were recalculated using a multivariate logistic regression model fit on the subpopulation only.Further analysis was performed in 4 subgroups: older inpatients (age ≥ 75 years), inpatients who received opioids before colonoscopy, inpatients with chronic kidney disease, and inpatients whose hospitalization was related to gastrointestinal bleeding. The gastrointestinal bleeding and kidney disease subpopulations were defined as patients with an http://links.lww.com/CTG/A789).Among 1,807 inpatients undergoing colonoscopy from January 2018 to January 2021 (full population), 293 (16.2%) and 1,514 (83.2%) patients received LV-BP and HV-BP, respectively. A comparison of the baseline patient characteristics between both groups is provided in Table P < 0.001) and with a trend toward shorter hospital LOS  compared with HV-BP (Table P = 0.35), patients receiving LV-BP had a significantly higher frequency of “Excellent”  preparations . No significant differences were seen for in-hospital mortality and physician-reported procedure complication rates between the 2 groups.While examining unadjusted outcomes within the full population, LV-BP was associated with a significantly shorter time to colonoscopy (median: 1.1 [Interquartile Range (IQR) IQR: 0.9–1.9] vs 1.5 [IQR: 1.0–2.1] days; http://links.lww.com/CTG/A789). Unadjusted outcomes in the propensity-matched population were similar to those in the full population  who received LV-BP were matched to 459/1,514 patients (30.3%) who received HV-BP. A comparison of baseline characteristics of the PSM populations is summarized in Table P < 0.001) (Table P < 0.12) . Adequate bowel preparation was not associated with LV-BP  for HV-BP . Overall, our findings demonstrate that LV-BP is associated with a significantly decreased time to colonoscopy without a difference in the frequency of adequate bowel preparation.We next developed a multivariate regression model fit on the PSM population to evaluate the adjusted association of LV-BP with each of the study outcomes. For our primary outcome, we found that LV-BP was significantly associated with a decreased time to colonoscopy  Table . Among thttp://links.lww.com/CTG/A789). The unadjusted patient outcomes in each of the matched subpopulations are presented in Table To perform exploratory investigations as to how LV-BP may affect outcomes in specific patient groups, we performed subgroup analyses for inpatients older than 75 years, receiving opioids before colonoscopy, with chronic kidney disease, and hospitalized for gastrointestinal bleeding. These patient groups were selected because rapid and adequate bowel preparation either is critical for their clinical management ,27 or reP < 0.05), followed by patients presenting with gastrointestinal bleeding , older patients , and patients with chronic kidney disease .LV-BP was associated with a significant decrease in time to colonoscopy among all 4 subgroups Figure . The impP < 0.01), patients with chronic kidney disease , and older patients . LV-BP was associated with a trend toward decreased LOS among patients who received opioids before the colonoscopy .The potential impact of LV-BP on decreasing hospital LOS was observed in this matched subgroup analysis Figure . LV-BP wP = 0.08).Finally, the odds of adequate bowel preparation with LV-BP were not significantly different compared with HV-BP in any of the subpopulations Figure . HoweverIn this study, we performed a retrospective PSM analysis assessing the impact of LV-BP on hospitalized patients undergoing colonoscopy. We found that LV-BP administration was associated with a significantly decreased time to colonoscopy compared with HV-BP. In addition, we found that LV-BP use was significantly associated with decreased hospital LOS for patients undergoing inpatient colonoscopy for gastrointestinal bleeding, for kidney disease, and for older patients (age ≥ 75 years), as well as strongly associated with decreased LOS for patients receiving opioids, suggesting that the benefits of the reduced preparation completion time may ultimately improve patient flow. Collectively, these results suggest that LV-BP use may reduce delays to inpatient endoscopy, which may potentially lead to improvements in hospital LOS and overall expenditures.The primary finding in our study was that LV-BP was associated with decreased time to colonoscopy in hospitalized patients compared with HV-BP. Importantly, the reduced time to colonoscopy occurred without reduction in the likelihood of adequate bowel preparation. In fact, patients given LV-BP had a significantly higher proportion of “Excellent” bowel preparation scores compared with those given HV-BP. Although the value of “Excellent” bowel preparation in comparison with that of “Good” for diagnostic yield warrants further investigation and may only lead to limited diagnostic benefits , 30, higWe also found that LV-BP may lead to decreased hospital LOS among certain inpatient subpopulations, indicating the potential benefits of LV-BP in reducing hospital costs and improving patient flow. For instance, we found that LV-BP was associated with a reduced hospital LOS among patients hospitalized specifically for gastrointestinal bleeding, a population in which adequate bowel preparation is particularly important to definitively identify and treat a bleeding source , 27. RedAmong our overall population, we found that LV-BP was associated with a nonsignificant trend toward reduced LOS. This may be because relatively healthy patients with fewer comorbidities who are able to tolerate high-volume preparations would not be expected to see the same benefits of using lower volume preparations. In addition, hospital LOS is an outcome that depends on a complex interplay between multiple patient and hospital-related factors , which eImportantly, we noted no increased adverse events in the LV-BP group compared with the HV-BP group. Low-volume preparations are hyperosmotic agents that carry theoretical risks of electrolyte disturbances and hypovolemia, particularly in patients with cardiac, renal, or hepatic dysfunction. This is particularly salient in the hospitalized population because there is a greater prevalence of such comorbidities, compared with outpatient populations. Our results suggest that with careful monitoring of laboratory results and administration of fluid as necessary, LV-BP use is likely safe for use in hospitalized patients.Our study had several limitations. First, we were limited by the retrospective nature of our study, which may lead to bias. However, we were able to use a propensity score-matched analysis that allowed us to account for many variables that may be important to our outcomes of interest. Moreover, each multivariate regression model controlled for patient and hospitalization characteristics identified through a feature selection algorithm, further reducing possible biases stemming from imperfect matches after propensity-matched analysis. In addition, although we could not assess the role of endoscopy scheduling and anesthesia availability to potential delays to colonoscopy, the fact that the endoscopy suite at the medical center examined in this study is open 7 days a week with a dedicated procedure room with anesthesia availability should mitigate such contributions. Second, we were unable to gather data explicitly describing tolerability of preparation. However, the decreased time to colonoscopy and similar rates of adverse events between the 2 groups strongly suggest that LV-BP is at least as well tolerated than standard HV-BP. Third, bowel preparation quality was documented according to the Aronchick scale, which has large interobserver variability compared with other scales including the Boston Bowel Preparation Scale . Fourth,Finally, our study was a single-center analysis, which limits generalizability. However, to the best of our knowledge, our study is the largest to date specifically exploring the impact of a LV-BP formulation on hospitalized patients undergoing colonoscopy. Moreover, our patient population was diverse, and thus, our study should be representative of most tertiary and quaternary care hospitals.Our study demonstrates that LV-BP use among inpatient populations can substantially reduce the time from bowel preparation to colonoscopy as well as related avoidable hospital bed days and potentially excess healthcare costs. Moreover, it builds on emerging data that suggest that LV-BPs may lead to similar degrees of bowel preparation quality compared with traditional HV-BPs in the hospitalized setting. Cost-effectiveness analyses and randomized controlled trials comparing the efficacy and tolerability of LV-BPs vs HV-BPs in hospitalized patients are needed to provide support in determining whether the use of LV-BPs should be widely adopted in inpatients requiring bowel preparation for colonoscopy.Guarantor of the article: James M. Richter, MD.Specific author contributions: Study concept and design: C.L.F.S., D.K.L., A.C.Z., R.L., and J.M.R. Acquisition of data: C.L.F.S. and J.H. Analysis and interpretation of data: C.L.F.S., D.K.L., M.A.B., P.C., B.D., S.E., A.M., K.S., B.J.Y., P.D., R.L., and J.M.R. Manuscript writing: C.L.F.S. and D.K.L. All authors approved the final draft submitted.Financial support: C.L.F.S. is a recipient of a Canadian Institutes of Health Research Fellowship.Potential competing interests: J.M.R. consults with Iterative Scopes  and WorldCare International . A.M. discloses a financial relationship with Amazon Pharmacy through a family member. All other authors have no disclosures.✓ Delays in inpatient colonoscopy are commonly caused by inadequate bowel preparation.✓ Few strategies exist to reduce the risk of inadequate bowel preparation in hospitalized patients.✓ Low-volume bowel preparation (LV-BP) use in hospitalized patients is associated with decreased time to colonoscopy.✓ LV-BP is associated with a similar frequency of adequate bowel preparation compared with traditional high-volume bowel preparation.✓ LV-BP is associated with decreased hospital length of stay in older patients, patients with chronic kidney disease, and patients presenting with gastrointestinal bleeding.