Coregonusintermundiasp. nov. and C.suspensussp. nov., are described. Coregonusnobilis Haack, 1882, C.suidteri Fatio, 1885, and C.zugensis Nüsslin, 1882, are redescribed. Genetic studies have shown that C.suidteri and C.zugensis are composed of several distinct species endemic to different lakes. The names C.suidteri and C.zugensis are restricted to the species of lakes Sempach and Zug, respectively. The whitefish populations previously referred to as C.suidteri and C.zugensis from Lake Lucerne are described as C.litoralissp. nov. and C.muellerisp. nov., respectively. Furthermore, the whitefish from Lake Zug that were previously referred to as C.suidteri are described as C.supersumsp. nov. A holotype is designated for C.supersum that was previously one of two syntypes of C.zugensis. The other syntype is retained for C.zugensis. Coregonusobliterussp. nov. is described from Lake Zug, and C.obliterus and C.zugensis from Lake Zug are extinct. Finally, we describe C.sarnensissp. nov. from lakes Sarnen and Alpnach. Coregonussuidteri from Lake Sempach shows strong signals of introgression from deliberately translocated non-native whitefish species, which questions if the extant population still carries a genetic legacy from the original species and thus may need to be considered extinct. Coregonussuspensus is genetically partially of allochthonous origin, closely related to the radiation of Lake Constance. It is therefore compared to all known and described species of Lake Constance: C.wartmanni Bloch, 1784, C.macrophthalmus Nüsslin, 1882, C.arenicolus Kottelat,1997, and C.gutturosus Gmelin, 1818.The taxonomy of the endemic whitefish of the lakes of the Reuss River system  and Lake Sempach, Switzerland, is reviewed and revised. Lake Lucerne harbours five species.  Coregonus spp.) are a classic example of recent postglacial adaptive radiations spanning the Palearctic temperate zone with several lakes in the boreal, subarctic, or pre-alpine regions harbouring multiple coexisting and closely related species  and from Lake Constance . Furthermore, we studied contemporary specimens of all whitefish species from Lake Lucerne and from Lake Sarnen . We also studied historical specimens of C.litoralis and C.muelleri from Lake Lucerne, of C.obliterus, C.zugensis, and C.supersum from Lake Zug and of all described species from Lake Constance.We studied the type material listed by Museum d’Histoire Naturelle, Genève (MHNG), Switzerland and in the Steinmann and Seehausen-Eawag collection of Eawag, Switzerland, now curated in theNaturhistorisches Museum Bern (NMBE).All contemporary specimens are part of the Seehausen-Eawag collection, which is planned to also be curated at a later stage at the NMBE. For the Steinmann collection some jars contain more than one fish and thus we provide the individual labels of each fish with ‘Eawag’ followed by the individual identification number, next to the NMBE number in brackets.Type material of all currently valid species , Lake Sarnen , Lake Sempach , Lake Zug , Lake Constance , Lake Lugano  and Lake Maggiore .The different whitefish species in this study derive from different lakes, namely Lake Lucerne  solutions. Muscle tissue and scales below the dorsal fin, as well as a part of the pectoral fin were taken for genetic and isotopic analysis and to determine the age of each fish. Each fish was photographed and then fixed in 4% formalin solution for at least 1 month and afterwards transferred through a series of ethanol of increasing concentration  to the final concentration of 70% for storage. Permits for collecting fish in the lakes were issued by the cantons adjacent to the lakes. In the field the fish were identified to species level as good as possible. Sex and fresh mass were noted. Immature fish, where the sex could not be determined externally, were examined internally. For the historical specimens the sex could only be determined when the abdominal cavity had already been opened. The age was determined by counting the annual growth rings of four scales under a confocal microscope following The collection of contemporary specimens differed slightly between projects, but in general was as follows: upon capture, fish were anaesthetised and subsequently euthanised with appropriate concentrations of phenoxyethanol, clove oil or tricaine methanesulfonate  for all loci per population, multilocus neutral genetic diversity within populations and pairwise genetic differentiation between populations  were calculated with Genodive  was reconstructed using the software package PHYLIP 3.69 (To identify genetic clusters (K) of populations and obtain genetic assignment proportion for individuals in a dataset with all whitefish species from Lakes Lucerne, Sarnen, Sempach, and Zug we used an individual-based Bayesian clustering approach implemented in STRUCTURE . The number of characters used for each analysis is explicitly mentioned in the results section. A description and illustrations of each character can be found in Table C.obliterus, C.zugensis, C.suidteri, C.gutturosus), which has been attributed to anthropogenic-induced eutrophication of many lakes in Switzerland in the middle of the 20th century with subsequent environmental changes that had effects on the morphological characters of whitefish species   , b, we dLDA) on morphological ratios (LDA) on all or a part of the measured characters to calculate the first two LDA ratios of characters that best separate the two species in each of the pairwise species’ comparisons. This was done among all contemporary specimens from lakes Lucerne and Sarnen and among all historical specimens from Lake Zug, as well as between historical specimens of the species from the lakes Lucerne and Zug that were previously all grouped under C.zugensis or C.suidteri. This method also allows to estimate the extent of shape change with size  which is given as δ and describes how good shape discriminates in comparison to size  of documented historical introductions of allochthonous whitefish from lakes Lucerne, Sempach, and Zug into Lake Sarnen (1888–1900: https://doi.org/10.5061/dryad.8cz8w9gvx). The specimens used for taxonomic work in this study and in NMBE). However, many of the specimens used for genetic work in this study have yet to be processed by the NMBE and are thus labelled in the accompanied dataset to this study with unique identifiers from the Seehausen-Eawag laboratory.All the data from this manuscript is available at Dryad Data Repository  contains the species C.litoralis, C.intermundia, C.suspensus and the whitefish population from Lake Alpnach. The two additional clusters in our analysis are a cluster  containing all whitefish from Lake Zug and Sempach and a cluster  containing the species C.sarnensis from Lake Sarnen. Few individuals from Lake Sempach that grouped in cluster 3 show high assignment likelihoods to cluster 2 of Lake Lucerne and vice versa. We have also identified a few individuals in Lake Sarnen that had moderately high individual assignment likelihoods to the Lake Lucerne cluster 2 and a few individuals in Lake Alpnach, a side-arm of Lake Lucerne that is connected to Lake Sarnen, that had high individual assignment likelihoods to the Lake Sarnen cluster 4  between the species ranged from 0.02 to 0.4 . nat. Coregonusschinziisupersumvar.lucernensisC.supersum). : Coregonus sp. ‘Bodenbalchen’: Coregonus sp. ‘large’: CoregonussuidteriC.supersum and C.suidteri). : Holotype. Contemporary specimen (year: 2007): NMBE-1078103, 326 mm SL, male; Switzerland: Lake Lucerne. Paratypes. All from Switzerland, Lake Lucerne: Contemporary samples : NMBE-1078064, NMBE-1078075, NMBE-1078079, NMBE-1078080, NMBE-1078083, NMBE-1078085, NMBE-1078091, NMBE-1078092, NMBE-1078098, NMBE-1078102-105, N = 12, 304–363 mm SL; Historical specimens : MHNG-717.046, NMBE-1076293-295 , N = 7, 222–392 mm SL.Coregonuslitoralis is a large whitefish  with strong pigmentation of all fins and body; greenish blue colour that sometimes has a pale mustard yellow undertone on the flanks above the lateral line; moderate to many pigmented small dots on the scales along the flank and the dorsum; deep bodied ; blunt snout; short head ; sub-terminal mouth; small eye  with a thick and triangular-shaped eye socket; short and stout caudal peduncle ; few and short gill rakers .Shape: Generally deep bodied with greatest body depth anterior of the dorsal fin. Dorsal profile from tip of snout to anterior origin of dorsal fin is strongly convex and ventral profile moderately convex from interorbital area to pelvic fin origin. Head short. Mouth short and sub-terminal. Rostral plate pronounced and a bit wider than deep resulting in a slightly rectangular shape. Tip of snout often blunt. Small eye with a thick and sickle cell-shaped eye-socket. Pectoral fin moderately tapered and moderately short. Dorsal fin long with anterior unbranched ray of the erected dorsal fin mostly 60–70 ° angle to body axis and slightly bent posteriorly at the end of the ray. Dorsal fin longest anteriorly and progressively shortening posteriorly with the outer margin of dorsal fin straight. Caudal peduncle stout and short with caudal fin moderately forked. Unbranched rays of anal fin slightly bent posteriorly. Anal fin longest anteriorly and progressively shortening posteriorly with the outer margin of anal fin mostly straight and only rarely slightly concave. Meristics: Few and short gill rakers. Colour: Pigmentation of fins and body overall strong in live specimens. Pectoral fin moderately pigmented at median to distal parts of the fin. All other fins are strongly pigmented. Silvery appearance along flanks with moderate to many pigmented small dots (aggregation of melanophores) on the scales along flank and dorsum. Distribution of dots bound to scale patterning such that dots are found at edge of the scales or at boundary point of two scales. Dorsally above lateral line the silvery appearance changes to a pale greenish or dark greenish blue colour. Seldomly, especially in older specimens, general greenish blue colour can have a pale mustard yellow ground colour   is larger than that of C.muelleri , C.suspensus  and C.intermundia   distinguishes i) Table . FurtherCoregonuslitoralis – CoregonusintermundiaC.litoralis differ from those of C.intermundia in being deeper bodied  and having a smaller eye   and a larger ‘snout length / maxilla length’ ratio (SN/M: 1.17–1.39 vs. 1.02–1.17) , having a longer dorsal fin base , a deeper caudal peduncle , a smaller eye , a deeper head  and shorter gill rakers   and a larger ‘caudal peduncle depth / predorsal length’ ratio (CD/PreD: 0.16–0.18 vs. 0.15–0.16) , having a longer dorsal fin base , a anteriorly longer erected and depressed dorsal fin , a deeper caudal peduncle  and shorter gill rakers   and a smaller ‘pectoral fin length / length of erected anterior part of dorsal-fin’ ratio (PecF2/DFAe: 0.84–0.92 vs. 0.94–1.1) , having a longer dorsal fin base , a shorter adipose fin base , a shorter head , a smaller eye , eye socket shape (sickle cell-shaped vs. roundish), deeper head , a shorter lower jaw , a shorter maxilla , a deeper snout , a wider head  and shorter gill rakers   and a larger ‘head depth / snout width’ ratio (HD/SW: 4.45–5.55 vs. 3.45–4.45) , having a deeper caudal peduncle , smaller eye , longer postorbital length , a deeper head , more transverse dorsal scales  and less gill rakers   overlaps mostly with the historical gill raker ranges given in C.litoralis can be distinguished from C.muelleri by having a larger ‘caudal peduncle depth / dorsal head length’ ratio (CD/DHL: 0.46–0.58 vs. 0.37–0.44)  and parts of the year on zooplankton   in an experimental setting . sp. ‘Schwebbalchen’: Holotype. Contemporary specimen (year: 2007): NMBE-1078097, 274 mm SL, male; Switzerland: Lake Lucerne. Paratypes. All from Switzerland, Lake Lucerne: Contemporary specimens (year: 2007): NMBE-1078076, NMBE-1078077, NMBE-1078078, NMBE-1078084, NMBE-1078086-1078090, NMBE-1078093-1078096, N =13, 232–278 mm SL.Coregonusintermundia is a medium-sized whitefish  with moderate pigmentation of all fins and the body; greenish blue colour on the flanks above the lateral line; moderate number of pigmented small dots on the scales along the flank; short head ; sub-terminal mouth; thick  and triangular-shaped eye socket; rather short and stout caudal peduncle .Shape: Only slightly deep bodied with greatest body depth anterior of dorsal fin. Dorsal profile from tip of snout to anterior origin of dorsal fin and ventral profile from interorbital area to pelvic fin origin are moderately convex. Head moderately short. Mouth moderately long and mostly sub-terminal and rarely terminal. Lower jaw moderately wide. Rostral plate equally wide as deep, not strongly pronounced with tip of the snout often more pointed than blunt. Eye-socket thick and sickle cell-shaped. Pectoral fin moderately tapered and moderately short. Dorsal fin rather short with anterior unbranched ray of erected dorsal fin mostly 70–80° angle to body axis, almost straight and only very slightly bent posteriorly at end of the ray. Dorsal fin longest anteriorly and progressively shortening posteriorly with outer margin of dorsal fin mostly straight and rarely concave. Caudal peduncle stout and moderately short with caudal fin moderately forked. Unbranched rays of anal fin slightly bent posteriorly. Anal fin longest anteriorly and progressively shortening posteriorly with outer margin of anal fin mostly straight and only rarely slightly concave. Meristics: Moderately many and moderately long gill rakers. Colour: Pigmentation of fins and body overall moderately strong in live specimens. Pectoral fin slightly pigmented at distal parts of fin. Pelvic fin moderately pigmented at the median to distal parts of fin. All other fins strongly pigmented. Silvery appearance along flanks with moderate number of pigmented small dots (aggregation of melanophores) on scales along flank and dorsum. Distribution of dots bound to scale patterning such that dots are found at edge of the scales or at boundary point of two scales. Dorsally above the lateral line the silvery appearance changes to a pale greenish to dark greenish blue colour and sometimes with pale mustard yellow ground colour. Dorsal part of head and snout around nostrils moderately pigmented. Pre-operculum and operculum silvery with one black spot on lower margin of pre-operculum. Preserved specimens pale in colouration with similar pigmentation as described for live specimens. The silvery, translucent, not coloured or unpigmented parts of body become yellowish brown, whereas pigmented parts are conserved and coloured parts  become brownish.C.litoralis and C.sarnensis are given under those species’ accounts.The differential diagnosis against Coregonusintermundia – CoregonussuspensusCoregonusintermundia can be distinguished from C.suspensus based on having a smaller ‘predorsal length / eye diameter’ ratio (PreD/ED: 9.92–10.59 vs. 10.73–11.4) , a shallower snout  and head  , a shorter head , smaller eye , differently shaped eye socket (sickle cell-shaped vs. roundish), a longer postorbital length  and a shorter lower jaw    from C.muelleri .  Table . FurtherCoregonusintermundia occurs in all basins of Lake Lucerne  at 3 years of age of C.intermundia is smaller than that of C.litoralis, considerably larger than that of C.muelleri and almost equal to that of C.suspensus .This species was not recognised by local fisheries, fisheries authorities, researchers, or the public before the works of Taxon classificationAnimaliaSalmoniformesCoregonidae042C18DB-D996-5D16-82E1-9B24F429D354https://zoobank.org/6063EEA5-E663-484D-A61F-6B349E18F81FCoregonus sp. ‘pelagic intermediate’: CoregonusC.intermundia). sp. ‘Schwebbalchen’: Holotype. Contemporary specimen (year: 2007): NMBE-1078100, 258.5 mm SL, male; Switzerland: Lake Lucerne. Paratypes. All from Switzerland, Lake Lucerne: Contemporary specimens (years: 2007): NMBE-1078081, NMBE-1078082, NMBE-1078099, NMBE-1078101, N = 4, 255–301.5 mm SL.Coregonussuspensus is a medium-sized whitefish  with weak pigmentation of the pectoral fin and moderate pigmentation of all other fins and body; greenish blue colour on the flanks above the lateral line; none to a few pigmented small dots on the scales on the flanks; tip of the snout pointy; triangular eye socket; many and moderately long gill rakers .Shape: Only slightly deep bodied with greatest body depth anterior of dorsal fin. Dorsal profile from the tip of snout to anterior origin of dorsal fin and ventral profile from interorbital area to pelvic fin origin is straight and only rarely is dorsal profile from tip of snout to interorbital area slightly convex. Head moderately short. Mouth moderately long and subtly sub-terminal. Lower jaw moderately wide. Rostral plate equally wide as deep, not strongly pronounced with tip of snout often more pointed than blunt. Eye-socket moderately thick and sickle cell-shaped. Pectoral fin moderately tapered and moderately short. Dorsal fin rather short with anterior unbranched ray of erected dorsal fin mostly 60–70° angle to body axis and slightly bent posteriorly. Dorsal fin longest anteriorly and progressively shortening posteriorly with outer margin of dorsal fin mostly concave and rarely straight. Caudal peduncle moderately stout with caudal fin moderately forked. Unbranched rays of anal fin moderately bent posteriorly. Anal fin is longest anteriorly and progressively shortening posteriorly with outer margin of anal fin mostly concave and only rarely straight. Meristics: Many and long gill rakers. Colour: Pigmentation of fins and body overall moderately strong in live specimens. Pectoral fin slightly pigmented at distal parts of fin. Pelvic fin moderately pigmented at median to distal parts of fin. All other fins strongly pigmented. Silvery appearance along flanks with few pigmented small dots (aggregation of melanophores) on scales along flank and dorsum. Distribution of dots bound to scale patterning such that dots are found at edge of scales or at boundary point of two scales. Dorsally above the lateral line silvery appearance changes to a pale greenish or dark greenish blue colour. Dorsal part of head and snout around nostrils moderately pigmented. Pre-operculum and operculum are silvery with one black spot on lower margin of pre-operculum. Preserved specimens pale in colouration with similar pigmentation as described for live specimens. Silvery, translucent, not coloured or unpigmented parts of the body brown-yellowish, whereas pigmented parts conserved and coloured parts  brownish.C.litoralis, C.intermundia, and C.sarnensis are given under those species’ accounts. Coregonussuspensus shows genetic ancestry contributions from whitefish of Lake Constance, besides its Lake Lucerne ancestry , a shallower head  and snout   , a shorter head , smaller eye , differently shaped eye socket (sickle cell-shaped vs. roundish), a longer postorbital length , a shorter lower jaw , a wider head  and a wider internarial width   and a larger ‘body depth / lower jaw’ ratio (BD/LJ: 2.71–3.33 vs. 2.01–2.63)  from C.muelleri   differentiates it from all species of Lake Constance, C.wartmanni (14.5% SL), C.macrophthalmus , C.gutturosus  and C.arenicolus .The shorter dorsal head length of Coregonussuspensus – CoregonuswartmanniCoregonussuspensus differs from C.wartmanni by having a longer adipose fin base , a larger eye , a shorter lower jaw , a shorter maxilla , longer gill rakers  and fewer branched pelvic fin rays  , a shorter lower jaw , a shorter maxilla , a wider head  and more lateral line scales  (Tables ) Tables .Coregonussuspensus – CoregonusgutturosusCoregonussuspensus differs from C.gutturosus by having a longer pelvic fin base , a shorter pelvic fin , a shorter pectoral fin , an anteriorly shorter erected dorsal fin , a shorter prepelvic length , a shallower head , a longer lower jaw , a shallower snout , longer gill rakers  and fewer gill rakers  , a shorter pelvic fin , a shorter pectoral fin base , an anteriorly shorter erected and depressed dorsal fin , an anteriorly shorter anal fin , a shallower caudal peduncle , a shorter dorsal head length , being shallower bodied , a larger eye , a shorter mouth width , a shallower snout , a less wide head , a less wide interorbital width , a less wide lower jaw , longer gill rakers , fewer predorsal scales  and more gill rakers (33–37 vs. 22–31)  at 3 years of age of C.suspensus is smaller than that of C.litoralis, considerably larger than that of C.muelleri and almost equal to that of C.intermundia , which grouped in their study closest to Lake Constance taxa and another species of partially allochthonous origin from Lake Thun, C.acrinasus. More recent work confirmed these findings, showing that C.suspensus has a genetic affinity  with C.wartmanni from Lake Constance  into Lake Lucerne, specifically in Lake Alpnach . These individuals have been named by the commercial fishermen after the colouration of their dorsum, which was blueish, as ‘Blaufelchen’ and were even noted in the commercial fisheries statistics of Lake Lucerne for a certain time period . This is the same local name that is given to C.wartmanni from Lake Constance. This could possibly be the first mention of C.suspensus in the scientific literature. However, already in the year 1661 Cysat described three forms of large-type whitefish in Lake Lucerne, the ‘Krautbalchen’, the ‘Schwembalchen’ and the ‘Steinbalchen’ and a local fisherman, J. Blättler, mentioned in 1908 that he was able to distinguish between three forms of large-type whitefish in the lake : MHNG-656.056, 207 mm SL, sex unknown; Switzerland: Lake Lucerne. Non-types. All from Switzerland, Lake Lucerne: Contemporary specimens (year 2005): NMBE-1078053-1078063, NMBE-1078065-1078074, N = 21, 253–315 mm SL. Historical specimens : MHNG-807.26, N = 2, 247 and 254 mm SL.Coregonusnobilis is a medium-sized whitefish with weak pigmentation of the pectoral and pelvic fin and moderate pigmentation of the anal, caudal, adipose and dorsal fin and body; pectoral and pelvic fin with yellowish undertone; pale olive-brown colouration on the flanks above the lateral line with pale greenish undertone that is most pronounced on dorsal part of the head; moderate number of pigmented small dots on the scales on the flanks; slender, elongated, and slightly torpedo-like body; caudal peduncle elongated ; tip of snout is fleshy and ranges from being square-like to roundish; large eye  with a thick  and triangular eye socket; many and long gill rakers .Shape: Slender body. Slender bodied with greatest body depth anterior of dorsal fin resulting in a slightly torpedo-like form. Dorsal and ventral profile similar and slightly arched. Dorsal and ventral profile from tip of snout to interorbital area mostly straight and then slightly convex to dorsal and pelvic fin origin respectively. Head moderately short. Mouth long and terminal or subtly sub-terminal. Lower jaw wide. Rostral plate equally wide as deep, quite pronounced with tip of snout fleshy and either roundish or blunt (square-like form). The eye is moderately large and that of historical specimens is larger than of contemporary specimens. Eye-socket thick and sickle cell-shaped. Pectoral fin moderately tapered and moderately long. Dorsal fin moderately long. Caudal peduncle narrow and elongated with caudal fin moderately forked and sometimes moderately to strongly asymmetrical. Meristics: Many and long gill rakers. Colour: Pigmentation of fins and body overall weak in live specimens. Pectoral and pelvic fin mostly transparent with yellowish ground colour, which is more pronounced in pectoral fin than pelvic fin. Pectoral fin rarely pigmented at distal part of fin and pelvic fin rarely moderately pigmented at median to distal parts of fin. Dorsal, anal, caudal and adipose fin moderately pigmented. Body weakly pigmented. Silvery appearance along flanks with moderate amount of pigmented small dots (aggregation of melanophores) on scales along flank and dorsum. Dorsally above the lateral line silvery appearance changes to a pale olive-brown and with a pale greenish ground colour that is most pronounced on dorsal part of head. Dorsal part of head and snout around nostrils moderately pigmented. Pre-operculum and operculum silvery with one black spot on lower margin of pre-operculum. Preserved specimens pale in colouration with similar pigmentation as described for live specimens. Silvery, translucent, not coloured or unpigmented parts of body become brown-yellowish, whereas pigmented parts are conserved and coloured parts  become brownish.C.nobilis to the contemporary specimens of the other species from Lake Lucerne. The differential diagnoses between C.litoralis, C.intermundia and C.suspensus, and C.sarnensis are given under those species’ accounts.We compare the contemporary specimens of Coregonusnobilis – CoregonusmuelleriCoregonusnobilis differs from C.muelleri by having an anteriorly shorter erected and depressed dorsal fin , a shorter caudal fin , a shorter dorsal head length , smaller eye , differently shaped eye socket (sickle cell-shaped vs. roundish), a deeper head and snout  and a wider head and lower jaw     . It is anomidae) . It is tto 214 m . During to 214 m  and ‘Vitto 214 m . Birrer Edelfisch.Taxon classificationAnimaliaSalmoniformesCoregonidaeB83A0FC4-C766-539C-B0F7-4E1947EE3E16https://zoobank.org/1D01BB7F-517B-4672-BC4D-B8700D56EFB2Coregonus ‘Albeli’: Coregonusexiguusalbellus : Coregonuslavaretusriusensis, oekot. nanus: C.zugensis and C.sarnensis). nat. Coregonus sp. ‘small’: Coregonus ‘Weissfelchen’: Coregonus ‘Weissfisch’: CoregonuszugensisC.zugensis). : Holotype. Contemporary specimen (year 2007): NMBE-1078123, 180 mm SL, male; Switzerland: Lake Lucerne. Paratypes. All from Switzerland, Lake Lucerne: Contemporary specimens (year 2007): NMBE-1078106–NMBE-1078122, NMBE-1078124–NMBE-1078135, N = 29, 158–198 mm SL. Historical specimens : NMBE-1076284, NMBE-1076289, NMBE-107628, NMBE-1076290 , NMBE-1076291, N = 8, 158–193 mm.Coregonusmuelleri is a small whitefish species  with weak pigmentation of all fins and body; pale olive-brown colouration on the flanks above the lateral line; elongate slender body; large eye  with a subtle triangular eye socket; tip of snout pointy; many and long gill rakers .Shape: Body elongated and slender. Greatest body depth anterior of dorsal fin. Ventral profile and dorsal profile similar and slightly arched. Dorsal and ventral profile from tip of snout to interorbital mostly straight and then slightly convex to dorsal and pelvic fin origin respectively. Head long. Snout long and tip of snout if often pointed and seldomly fleshy resulting in a not pronounced rostral plate. Mouth long and terminal. Large eye with a subtle sickle cell-shaped (seldom roundish) eye-socket in the historical specimens and a mostly roundish (seldom sickle cell-shaped) eye-socket in the contemporary specimens. The eye of the historical specimens is larger than those of the contemporary specimens. Pectoral fin moderately long and tapered. Anterior unbranched ray of the erected dorsal fin ranges from almost vertically straight to an ~ 70–80° angle to body axis and only bent slightly posteriorly at end of the ray. Caudal peduncle narrow and elongated with caudal fin forked and sometimes moderately to strongly asymmetrical with often ventral part being longer. Unbranched rays of anal fin straight and rarely bent posteriorly at end of ray. Anal fin longest anteriorly and progressively shortening posteriorly with outer margin of the anal fin slightly concave. Meristics: Many and long gill rakers. Colour: Pigmentation of fins and body weak in live specimens. Pectoral fin transparent and pelvic and anal fin mostly transparent. Pectoral fin very rarely pigmented at distal part of the fin and anal and pelvic fin rarely moderately pigmented at median to distal parts of fin. Dorsal, caudal and adipose fin moderately pigmented. Silvery appearance along flanks. Dorsally above the lateral line silvery appearance changes to a pale olive-brown. Dorsal part of head and snout around nostrils moderately pigmented. Pre-operculum and operculum silvery with one black spot on lower margin of the pre-operculum. Preserved specimens pale in colouration with similar pigmentation as described for live specimens. In contemporary specimens silvery, translucent, not coloured or unpigmented parts of body become brown-yellowish, whereas pigmented parts are conserved and coloured parts  become brownish. In historical specimens all body parts are brownish.C.litoralis, C.intermundia, C.suspensus, C.nobilis and C.sarnensis and against the historical specimens of C.litoralis from Lake Lucerne and C.zugensis from Lake Zug are given under those species’ accounts.The differential diagnoses against the contemporary specimens of Coregonusmuelleri occurs in all basins of Lake Lucerne  historically and is today the most abundant and commercially important whitefish species in Lake Lucerne  .rne Fig.  except f Lucerne . Coregonnomidae) . It is an caught . It has n caught . Coregonto 200 m . HoweverC.nobilis.The species is named after the late Dr. Rudolf Müller, a fisheries biologist and former department head and research group leader at EAWAG, Center for Ecology, Evolution and Biogeochemistry (CEEB) in Kastanienbaum, Switzerland. He dedicated a large part of his career to understanding the ecology of whitefish in Swiss lakes, and confirmed the re-discovery of Albeli.Taxon classificationAnimaliaSalmoniformesCoregonidaeBA3CB832-F9F2-546A-AF69-6C8564F07BDDhttps://zoobank.org/34B59895-283B-4081-B964-78FFA2FF9C32Coregonuslavaretusriusensis, oekot. primigenius: C.supersum, C.suidteri, and C.litoralis). nat. Coregonus ‘Sarnerbalchli’: Coregonus ‘Sarnerfelchen’: Coregonus sp. ‘Sarnerfelchen’: CoregonuszugensisC.muelleri and C.zugensis). : Holotype.NMBE-1078159, 230 mm SL, male; Switzerland: Lake Sarnen. Paratypes. All from Switzerland, Lake Sarnen: NMBE-1078143–NMBE-1078155, NMBE-1078157, NMBE-1078158, NMBE-1078160–NMBE-1078169, NMBE-1078171 – NMBE-1078173, NMBE-1078174, NMBE-1078175, N = 27, 188–261.5 mm SL.Coregonussarnensis is a medium-sized whitefish  with weak pigmentation of the pectoral and pelvic fin and moderate pigmentation of the anal, caudal, adipose and dorsal fin and body; pale green to pale olive-brown colouration on the flanks above the lateral line; moderate number of pigmented small dots on the scales on the flanks; slender, elongated body; caudal peduncle mostly elongated ; tip of snout is fleshy, roundish, and often has an ~ 40–50° angle to the body axis anterior of the eye, such that the profile from the tip of the snout to the vertical projection where the anterior part of the eye crosses the dorsal profile is straight and afterwards slightly convex; large eye ; many and long gill rakers .Shape: Body elongated and slender. Greatest body depth anterior of dorsal fin resulting in a slightly torpedo-like form. Ventral profile and dorsal profile similar and slightly arched. Dorsal and ventral profile from tip of snout to interorbital mostly straight and then slightly convex to dorsal and pelvic fin origin respectively. Head moderately long. Snout often has an ~ 40–50° angle to body axis anterior of eye, such that profile from tip of snout to vertical projection where anterior part of eye crosses dorsal profile is straight and afterwards slightly convex. Tip of snout if often roundish and seldomly fleshy resulting in a not strongly pronounced rostral plate. Mouth thick , long and often terminal and only rarely slightly sub-terminal. Large eye with a variable eye-socket shape ranging from sickle cell-shaped to roundish. Pectoral fin moderately long and tapered. Anterior unbranched ray of erected dorsal fin ranges from almost vertically straight to an ~ 70–80° angle to body axis and only bent slightly posteriorly at end of ray. Caudal peduncle often narrow and elongated (seldomly stout) with caudal fin forked. Unbranched rays of anal fin straight. Anal fin longest anteriorly and progressively shortening posteriorly with outer margin of anal fin slightly concave. Meristics: Many and long gill rakers. Colour: Pigmentation of fins and body moderate in live specimens. Pectoral fin transparent and pelvic and anal fin mostly transparent. Pectoral fin is only pigmented at distal part of fin and anal and pelvic fin are moderately pigmented at median to distal parts of fin. Dorsal, caudal and adipose fin moderately pigmented. Silvery appearance along flanks. Dorsally above lateral line silvery appearance changes from a pale green colouration  on scales. Preserved specimens pale in colouration with similar pigmentation as described for live specimens. Silvery, translucent, not coloured or unpigmented parts of body become brown-yellowish, whereas pigmented parts are conserved and coloured parts  become brownish.Coregonussarnensis – CoregonuslitoralisCoregonussarnensis can be differentiated from C.litoralis by having a shorter dorsal fin base , longer head , larger eye , a shallower head , less wide interorbital width , longer gill rakers  and more gill rakers    and a larger eye cavity  , a longer dorsal head length , longer head  and larger eyes   , longer caudal fin , deeper caudal peduncle , longer dorsal head length , larger eye  and a shallower snout   , being deeper bodied , having a wider eye socket  and wider head  . Thus, the spawning season of C.sarnensis is known only for November  and it spawns at depth of 20 metres down to the lake bottom at 50 metres.e Sarnen . Lake Sae Sarnen . The occe Sarnen : fig. S1sarnensis refers to Sarnen, a village on the shores of the lake to which it gave its name. An adjective.The specific name Sarnerfelchen, Sarneralbeli.Taxon classificationAnimaliaSalmoniformesCoregonidaeE28F2697-CFC6-530B-8FFB-9929C9CCD124https://zoobank.org/7502CA0A-1E34-4DC5-825D-DFEE7F4B1E0CCoregonus ‘Balchen’: CoregonuscrassirostriscompactusC.zugensis). : Coregonuslavaretusriusensis, oekot. primigenius: C.sarnensis, C.suidteri, and C.litoralis). nat. Coregonusschinziihelveticusvar.zugensisC.litoralis) : CoregonussuidteriC.litoralis and C.suidteri). : Coregonus sp. ‘Zugerbalchen’: Coregonus sp. ‘Zugerseebalchen’: Holotype. Historical specimen (year 1939): NMBE-1076275, 288 mm SL, male; Switzerland: Lake Zug. Paratypes. All from Switzerland, Lake Zug: Historical specimens : NMBE-1076265, NMBE-1076267, NMBE-1076268, NMBE-1076277, MHNG 2786.063, N = 5, 263–411 mm SL.Coregonussupersum is a large whitefish species with strong pigmentation of all fins and the body; greenish blue colour on the flanks above the lateral line; deep bodied ; blunt snout; short head ; sub-terminal mouth; small eye  with a thick and triangular-shaped eye socket; short and stout caudal peduncle ; few and short gill rakers .Shape: Generally, deep bodied with greatest body depth anterior of dorsal fin. Dorsal profile from tip of snout to anterior origin of dorsal fin is strongly convex and ventral profile moderately convex or almost straight from interorbital area to the pelvic fin origin. Head short. Mouth short, wide and sub-terminal. Rostral plate pronounced and a bit wider than deep resulting in a slightly rectangular shape. Tip of snout often blunt. Small eye with a thick and mostly sickle cell-shaped eye-socket. Pectoral fin moderately tapered and moderately short. Dorsal fin long. Caudal peduncle stout and short with caudal fin moderately forked. Unbranched rays of anal fin slightly bent posteriorly. Anal fin longest anteriorly and progressively shortening posteriorly with outer margin of anal fin mostly straight and only rarely slightly concave. Meristics: Few and short gill rakers. Colour: Pigmentation of fins and body overall strong. Pectoral fin moderately pigmented at the median to distal parts of the fin. All other fins are strongly pigmented. Silvery appearance along the flanks. The preserved specimens have moderate to many pigmented small dots (aggregation of melanophores) on the scales along the flank and the dorsum. Dorsally above the lateral line the silvery appearance changes to a greenish blue colour. The dorsal part of the head and the snout around the nostrils is strongly pigmented. The pre-operculum and operculum are silvery with one black spot on the lower margin of the pre-operculum. Preserved specimens are pale in colouration with similar pigmentation as described for live specimens. Preserved fish are brownish in colouration.Coregonussupersum – CoregonuszugensisCoregonussupersum can be differentiated from C.zugensis by having a shorter head , a smaller eye , a longer upper and lower jaw and maxilla , a deeper snout , shorter gill rakers  and less gill rakers   , a smaller eye  and longer longest gill raker   and a larger ‘adipose fin base / eye depth’ ratio (AdFB/ED: 1.15–1.42 vs. 0.64–1) (Table 1) Table .Coregonussupersum – CoregonuslitoralisCoregonussupersum can be differentiated from C.litoralis by having a shorter dorsal head length , a shorter middle gill raker  and by having a larger ‘mouth width / snout depth’ ratio (MW/SD: 1–1.21 vs. 0.75–1) , a shallower pectoral fin base , a shorter erected anterior anal fin , a longer distance from the posterior part of the adipose fin to the caudal fin base , a shorter pre-dorsal distance , a smaller eye , a less wide and shorter mouth , a wider interorbital width , a less wide internarial width  and lower jaw width  . sp. ‘Albeli-Albock’: CoregonuscrassirostriscompactusC.supersum). : Coregonuslavaretusriusensis, oekot. primigenius nanus: C.muelleri and C.sarnensis). nat. Coregonusmacrophthalmusvar.zugensis : CoregonuswartmannicompactusC.obliterus). : Coregonus sp. ‘Zugeralbeli’: Coregonus ‘Zugerseealbeli’: Syntypes. All from Switzerland, Lake Zug: Historical specimens : MHNG-715.093, NMBE-1076263 , NMBE-1076264 , NMBE-1076266 , NMBE-1076275 , N = 12, 173–236mm SL.Coregonuszugensis is a small whitefish species with weak pigmentation of all fins and body; pale olive-brown colouration on the flanks above the lateral line; elongate slender body ; large eye  with a subtle triangular eye socket ; many and long gill rakers .Shape: Body elongated and slender. Greatest body depth anterior of the dorsal fin. Ventral profile and dorsal profile similar and slightly arched. Dorsal and ventral profile from tip of snout to interorbital mostly straight and then slightly convex to dorsal and pelvic fin origin respectively. Head long. Snout long and tip of snout if slightly pointed resulting in a not strongly pronounced rostral plate. Mouth long and terminal. Large eye with a subtle sickle cell-shaped (seldom roundish) eye-socket. Pectoral fin long and tapered. Caudal peduncle moderately stout. Meristics: Many and long gill rakers. Colour: Pigmentation of fins and body weak in live specimens. Pectoral fin transparent and pelvic and anal fin mostly transparent. Pectoral fin very rarely pigmented at the distal part of the fin and the anal and pelvic fin rarely moderately pigmented at the median to distal parts of the fin. Dorsal, caudal and adipose fin moderately pigmented. Silvery appearance along the flanks. Dorsally above the lateral line the silvery appearance changes to a pale olive-brown. Pre-operculum and operculum with one black spot on the lower margin of the pre-operculum. Preserved specimens are brownish in colouration.C.supersum from Lake Zug are given under that species account.The differential diagnoses against the historical specimens of Coregonuszugensis – CoregonusobliterusCoregonuszugensis can be differentiated from C.obliterus by having a wider adipose fin base , a smaller eye cavity , a longer maxilla , a shallower snout , a less wide interorbital  and longer and more gill rakers . Based on ratios C.zugensis can be differentiated from C.obliterus by having a smaller ‘eye diameter / maxilla’ ratio (EC/M: 1.11–1.34 vs. 1.38–1.65) , a smaller eye cavity  and a deeper head . Based on ratios C.zugensis can be differentiated from C.muelleri by having a smaller ‘caudal peduncle depth / prepelvic length’ ratio (CD/PreP: 0.13–0.15 vs. 0.12–0.13) (Tables ) Tables .Coregonuszugensis occurred in Lake Zug and is extinct today  and the ‘Albeli-Albock’ (Coregonuswartmannicompactus). Interestingly, C.supersum and the Suppl. material C.zugensis, spawned in comparison to C.obliterus (‘Albock’) later in the year from mid-October to late December in deep waters of the lake. C.zugensis, spawns in the deeper parts of the lake (‘fond’ in French) and that the ‘Albock’, C.obliterus, spawns in even deeper waters of the lake (‘grand fond’ in French). Coregonuswartmannicompactus, which includes several other small and pelagic whitefish species from other lakes. This and the number and length of gill rakers of C.zugensis (many and long gill rakers) suggests, based on the functional properties of the number of gill rakers experimentally tested with specimens of other whitefish species from lakes Thun and Lucerne . sp. ‘Albeli-Albock’: Coregonuslavaretusriusensis, oekot. primigenius nanus: C.muelleri and C.sarnensis). nat. CoregonuswartmannicompactusC.zugensis). : Holotype. Historical specimen (year 1937): NMBE-1076268 (EAWAG-284-1), 281 mm SL, sex male; Switzerland: Lake Zug. Paratypes. All from Switzerland, Lake Zug: Historical specimens : NMBE-1076268 , NMBE-1076271, NMBE-1076276, NMBE-1076906 , N = 6, 250–288 mm SL.Coregonusobliterus is a small whitefish species with moderate pigmentation of all fins and body; elongated slender body ; short mouth ; pronounced rostral plate; very large eye  with a subtle triangular (seldom roundish) eye socket; few and very short gill rakers .Shape: Body elongated and slender. Greatest body depth anterior of the dorsal fin. Ventral profile and dorsal profile similar and slightly arched. Dorsal and ventral profile from tip of snout to interorbital mostly straight and then slightly convex to dorsal and pelvic fin origin respectively. Head long. Snout often 40–50° angle to the body axis anterior of the eye, such that the profile from the tip of the snout to the vertical projection where the anterior part of the eye crosses the dorsal profile is straight and afterwards slightly convex. Snout moderately long and tip of snout quite deep with a strongly pronounced rostral plate. Mouth short and terminal to sub-terminal. Very large eye with a subtle sickle cell-shaped (seldom roundish) eye-socket. Pectoral fin short and tapered. Caudal peduncle moderately stout. Meristics: Few and very short gill rakers. Colour: Pigmentation of fins and body moderate in preserved specimens. All fins moderately pigmented at the median to distal parts of the fin. Operculum with one black spot on the lower margin of the pre-operculum. Preserved specimens are brownish in colouration.C.supersum and C.zugensis from Lake Zug are given under those species’ accounts.The differential diagnoses against the historical specimens of Coregonusobliterus occurred in Lake Zug and is extinct today  and the ‘Albeli-Albock’ (Coregonuswartmannicompactus). Interestingly, C.zugensis, spawns in the deeper parts of the lake (‘fond’ in French) and that the ‘Albock’, C.obliterus, spawns in even deeper waters of the lake (‘grand fond’ in French). Based on the findings that Lake Zug did harbour three species of whitefish and taking into account the spawning table and notes referring to the table in C.obliterus. It seems based on the phenotype of C.obliterus including the spawning time and depth and the few and short gill rakers of this species, that this species must have occupied a similar ecological niche as is known for two whitefish species from two other lakes in Switzerland. C.gutturosus (today extinct) from Lake Constance and C.profundus from Lake Thun share many ecological and morphological characters with C.obliterus. More is known about the biology of these two species; C.gutturosus was (extinct today) and C.profundus is a profundal specialist feeding predominantly on benthic prey items and living and spawning in great water depths.obliterus means ‘erased from memory’ or ‘forgotten’. The name highlights that this species was forgotten for more than a century in the scientific literature. An adjective.The name in Latin We suggest the German name Zugeralbock.Taxon classificationAnimaliaSalmoniformesCoregonidaeFatio, 18856A3D31B3-779E-52A9-9F77-C9DDF814A9E1Coregonusannectus : Coregonusannectusballeoides : Coregonuslavaretusriusensis, oekot. Primigenius: C.sarnensis, C.supersum, and C.litoralis). nat. CoregonusSchinziihelveticusvar.zugensis : CoregonusSchinziihelveticusvar.lucernensis : Coregonus ‘Sempacherballen’: CoregonussuidteriC.litoralis and C.supersum). : Coregonuslavaretus fera natio vogti: Coregonuslavaretus natio riusensis: Syntypes. All from Switzerland, Lake Sempach: Historical specimens : MHNG-715.089, MHNG-816.026, N = 2, 311 mm and 312 mm SL, sex unknown; MHNG-676.007, branchial arch, which probably belongs to one of the syntypes (used for gill raker measurements).Coregonussuidteri is a large whitefish species with strong pigmentation of all fins and the body; greenish blue colour on the flanks above the lateral line; deep bodied (body depth: 25.4 and 29% SL); blunt snout; short head (20 and 22% SL); sub-terminal mouth; moderately large eye (eye diameter: 21.9 and 23.9% HL) with a thick (4.5 and 6.5% HL) and triangular-shaped eye socket; short and stout caudal peduncle ; many but rather short gill rakers .Shape: Generally, deep bodied with greatest body depth anterior of dorsal fin. Dorsal profile from tip of snout to anterior origin of dorsal fin strongly convex and ventral profile moderately convex or almost straight from interorbital area to pelvic fin origin. Head short. Mouth short, wide and sub-terminal. Rostral plate pronounced. Tip of snout blunt. Large eye with a thick and sickle cell-shaped eye-socket. Pectoral fin moderately tapered and short. Dorsal fin long. Caudal peduncle stout and short. Meristics: Many but rather short gill rakers. Colour: Pigmentation of fins and body overall strong with a silvery appearance along the flanks and dorsally above the lateral line the silvery appearance changes to a greenish blue colour , shorter snout , a larger eye cavity , a shorter postorbital length , a deeper head , a less wide interorbital width , a wider internarial width  and a wider lower jaw   historical records report several incidences of introductions of whitefish from other Swiss, German and even North American lakes into Lake Sempach  from Lake Lucerne into Lake Sempach. C.maraena and whitefish individuals from North America. Most likely many different whitefish species from Swiss lakes and beyond were introduced. This is not unique to Lake Sempach and was unfortunately common practice at that time. These deliberate introductions from other lakes took place after the population decline of whitefish in Lake Sempach, which were attributed to the lowering of the lake level in the 19th century (th century Lake Sempach seemed to harbour a large and productive whitefish fishery according to fisheries catch accountings (th century (375–750 grams) which led th century. C.suidteri that were given to Victor Fatio in the 1880s by Otto Suidter (C.suidteri), which he could examine in the last half of the 20th century, should be regarded as a ‘mixtum compositum’, i.e., a mixed population composed of different whitefish species including the original large-type whitefish species of Lake Sempach. Indeed, th century of smaller individuals of a putative small-type species resulting in fewer but larger individuals of a second large-type species, 2) deliberate introductions in the late 19th and early 20th century, and 3) a strong anthropogenic-induced eutrophication during the last half of the 20th century in Lake Sempach, which may have been accompanied (as has been shown for other lakes) by population collapse, speciation reversal, and extinction , NMBE-1076232 (Eawag-248-1), NMBE-1076233 , NMBE-1076232 , N = 10, 169–292 mm SL.: Taxon classificationAnimaliaSalmoniformesCoregonidaeKottelat, 1997B347496D-3707-59E3-B038-5C7172043F50Holotype.NMBE-1076223 (Eawag-239-1), 296 mm SL, sex unknown; Switzerland: Lake Constance. Paratypes.NMBE-1076223 , N = 3, 289–314 mm SL.(year 1950): Taxon classificationAnimaliaSalmoniformesCoregonidaeNüsslin, 1882E71AAC33-ACDA-50B1-BFB0-BEE0D03227F1Syntypes: MHNG 716.052, MHNG-716.051, MHNG-816.02, MHNG-715.094 (N = 2: MHNG-715.094), NMBE-1076211 , N = 7, 193–235 mm SL.: Taxon classificationAnimaliaSalmoniformesCoregonidaeBloch, 1784CF19C408-D928-5A2A-999F-43E6525B40B8Non-type: NMBE-1076206, Switzerland, 301 mm SL.(year 1895): C.nobilis. The species key needs to be followed completely to be able to distinguish C.nobilis from all other whitefish species of Lake Lucerne.This identification key is based on contemporary specimens of the five species from Lake Lucerne. The key leads in two distinct ways to All pre-alpine whitefish species have been shown based on phylogeographic studies to belong to a monophyletic clade of hybrid origin involving two anciently divergent glacial lineages that must have come into secondary contact several hundred thousand years after their separation. Independent events of intra-lacustrine speciation led to a series of adaptive radiations in each major lake system north of the Alps . Up to sC.suidteri and C.zugensis, which were previously thought to naturally occur in several lakes in Switzerland, namely for C.suidteri lakes Lucerne, Zug, Sempach, Hallwil, and Baldegg and for C.zugensis lakes Lucerne and Zug  group with the whitefish species from Lake Sarnen, C.sarnensis. Lake Zug and Lake Sempach have experienced strong anthropogenic-induced eutrophication, which is often accompanied by population collapse, speciation reversal, and extinction of endemic whitefish species (C.zugensis and C.obliterus in Lake Zug and possibly of C.suidteri in Lake Sempach. In the case of Lake Zug nothing is known about the possibility of speciation reversal, whereby extinct species leave traces in genomes of extant species through introgressive hybridisation. Future research will be needed to understand if the extant whitefish population of Lake Zug and the extant populations of the lakes Maggiore and Lugano that we group to the species C.supersum shows signs of introgression of the extinct species of Lake Zug, C.zugensis and C.obliterus, respectively.Many Swiss lakes experienced strong anthropogenic-induced eutrophication which among the lakes in this study was pronounced in lakes Zug and Sempach. It has been accompanied by population collapse, speciation reversals, and extinction of Swiss whitefish , b. Furt species , b. ThisMany of the unresolved Swiss whitefish diversity has been revised with this study coupled with the recent revision by


Dear editor,1 It is known that bone marrow adipocytes (BMA) can control bone mass by modulating the bone morphogenetic protein (BMP) and other signaling pathways. BMAs can secret soluble factors, which impact osteoblasts, osteoclasts, and osteocytes.2 Sclerostin is a potent inhibitor of bone acquisition that antagonizes Wnt/β-catenin signaling. Deleting sclerostin was recently reported to protect against cardiovascular disease.3 Furthermore, neutralizing monoclonal antibodies against sclerostin increase bone mass and are utilized to treat osteoporosis. Previous studies revealed that global ablation of sclerostin increased both trabecular and cortical bone mass4 and that sclerostin produced by the osteocytes located in the bone matrix negatively regulated bone mass in mice.5 However, it is not known whether sclerostin derived from other cell types also contributes to bone formation.The comorbidity of obesity and osteoporosis illustrates the communication and coordination of adipose and bone tissues. Leptin and adiponectin derived from adipocytes regulate osteoblast formation and function to impact bone mass through direct and indirect mechanisms.Sost gene, which encodes sclerostin, using the Adipoq-Cre that mainly targets adipose lineage cells. We found that mice lacking sclerostin in adiponectin-expressing cells (SostAdipoq) had similar body weight, fat mass, and organs weight compared to their control littermates   Fig. . Note: Ttes Fig. . We perfice Fig. . The inctes Fig. . We nextSost deletion did not change the serum levels of leptin and adiponectin, which are known to impact bone mass   Fig.  and colo-F) Fig. . IF stai-F) Fig. . The expice Fig. . Notablyice Fig. . Thus, fion Fig. . This unsupplement material


Staphylococcus aureus is a prevalent foodborne bacterium causing significant morbidity, mortality, and economic loss, due especially to pathogenic and multidrug-resistant (MDR) strains. This study focused on determining the prevalence of S. aureus in chicken meat in Egyptian markets and assessing the effectiveness of natural phenolic compounds as novel antibacterial agents against MDR S. aureus. The study found that 91.3% of chicken meat parts were contaminated with S. aureus, with 81.8% of the isolates being MDR. Twenty-two antibiotic resistance patterns were identified, and six strains showed the highest combination of virulence and resistance genes. The phenolic compound hydroquinone exhibited the most potent antibacterial activity compared to other compounds, making it a potential alternative to conventional antibiotics against the pathogenic MDR S. aureus found in raw chicken meat. This study highlights the need for urgent interventions to improve hygiene for safer meat in Egyptian markets and suggests hydroquinone as an effective natural compound for inhibiting foodborne pathogens.Staphylococcus aureus is one of the most widespread foodborne bacteria that cause high morbidity, mortality, and economic loss, primarily if foodborne diseases are caused by pathogenic and multidrug-resistant (MDR) strains. This study aimed to determine the prevalence of S. aureus in chicken meat in Egyptian markets. Thus, this study might be the first to assess the efficiency of different natural phenolic compounds as novel antibacterial agents against MDR S. aureus pathogens isolated from raw chicken meat in the Egyptian market. The incidence and quantification of pathogenic S. aureus were detected in retail raw chicken meat parts . In total, 73 out of 80 (91.3%) of the chicken meat parts were contaminated, with S. aureus as the only species isolated. Of the 192 identified S. aureus isolates, 143 were coagulase-positive S. aureus and 117 isolates were MDR . Twenty-two antibiotic resistance profile patterns were detected. One strain was randomly selected from each pattern to further analyze virulence and resistance genes. Extracted DNA was assessed for the presence of antibiotic-resistance genes, i.e., vancomycin-resistance (vanA), aminoglycosides-resistance (aacA–aphD), apramycin-resistance (apmA), and methicillin-resistance (mecA), penicillin-resistance (blaZ), and virulence genes staphylococcal enterotoxins (sea and seb), Panton–Valentine leucocidin (pvl), clumping factor A (clfA), and toxic shock syndrome toxin (tst). Clustering analyses revealed that six S. aureus strains harbored the most virulence and resistance genes. The activity of hydroquinone was significantly higher than thymol, carvacrol, eugenol, and protocatechuic acid. Therefore, phenolic compounds, particularly hydroquinone, could potentially alternate with conventional antibiotics against the pathogenic MDR S. aureus inhabiting raw chicken meat. Hence, this study indicates that urgent interventions are necessary to improve hygiene for safer meat in Egyptian markets. Moreover, hydroquinone could be a natural phenolic compound for inhibiting foodborne pathogens. Foodborne diseases (FBDs) arise from the consumption of food containing physical, chemical, or biological hazards, with most infections caused by biological agents such as bacteria, viruses, and parasites. FBDs pose significant health risks and present obstacles to sustainable development in all countries, particularly in developed countries ,2. The mStaphylococcus aureus, are prevalent in ASF. S. aureus, typically found as a commensal bacterium in humans, can act as an opportunistic pathogen, leading to a wide range of diseases from minor skin infections to severe and even fatal conditions [S. aureus and several coagulase-positive staphylococci (CPS) species, including foodborne diseases, produce various enterotoxins that can result in diverse clinical symptoms [S. aureus contamination, necessitating monitoring and control of its incidence in retail raw chicken meat, especially in developed countries [Among the main causes of foodborne illnesses, pathogenic bacteria, especially Gram-positive nditions . In partsymptoms . Despitesymptoms . Chickenountries .S. aureus exhibits a notable diversity in virulence and resistance genes, contributing to its rapid and aggressive pathogenicity [S. aureus in the food industry has led to far-reaching economic, social, and health implications [S. aureus strains have been found to harbor antibiotic-resistance genes, reducing the effectiveness of commonly used antibiotics in veterinary treatment [S. aureus exhibits a wide array of virulence genes. Moreover, the contamination of raw chicken meat and poultry products with S. aureus and its enterotoxins can pose a health risk, especially when stored at room temperature. Therefore, it is crucial to investigate the prevalence of resistance and virulence genes in the pathogens present in raw chicken meat to gather data on the extent and progression of this problem and to explore effective management strategies.genicity . The emegenicity ,13. The genicity ,15. Notaications . Zoonotireatment ,18. Abolreatment  reportedIn addition, bacterial biofilm development is another critical element contributing to a severe problem during infection treatment . BiofilmConsumers and the food industries are paying much attention to the use of natural antibacterial agents in the food industry. This is due to three essential aspects. First, the group of microorganisms, including foodborne pathogens, that are not only antibiotic-resistant but also more tolerant to various food processing and preservation methods has dramatically increased due to the abuse and improper management of antibiotics. Researchers are now more interested in creating and using natural ingredients in meals due to consumers’ growing knowledge of the possible health risks associated with synthetic preservatives compared to the advantages of natural additives. The second aspect represented is that this has compelled the food industry to search for substitute preservatives to improve food quality and safety. Because natural phenolic compounds exhibit antibacterial qualities that are effective against a wide variety of foodborne pathogens, substances produced from natural sources have the potential to be utilized to ensure the safety of food. The third factor is their bioactivities, such as antioxidant, anti-aging, cardioprotective, anticancer, and anti-inflammatory properties .Phenolic compounds, naturally present in essential oils, serve as common antibacterial agents . DependiIn Egypt, most citizens regularly buy fresh food, particularly fresh chicken meat, from traditional markets commonly known as wet markets . These tIn contrast, supermarkets typically maintain better standards, with access to clean water, refrigeration systems, and suitable processing facilities. As a result, poultry products sold in supermarkets may be comparatively safer than those in traditional marketplaces. However, supermarkets are not as prevalent in Egypt as in some high-income countries. Moreover, data on foodborne disease burdens in developing countries like Egypt, Cambodia, and Libya are scarce, as monitoring efforts are relatively limited compared to high-income nations with more extensive information resources .S. aureus strains with different virulence characteristics. Most existing research on phenolics’ effects has primarily focused on just one or two reference strains [S. aureus strains in chicken meat from Egyptian markets, while also assessing the presence of resistance and virulence genes within these strains. Additionally, the study aims to evaluate the bioactivity of natural phenolic compounds as antimicrobial and antibiofilm agents. The findings of this research will provide valuable insights for food safety management in the Egyptian market, shedding light on the occurrence of pathogenic MDR S. aureus strains. Moreover, this study proposes a viable approach to combat foodborne S. aureus pathogens by utilizing natural phenolic compounds as alternative antibacterial agents instead of conventional antimicrobial agents.Limited research has explored the antimicrobial activity of phenolic compounds against zoonotic MDR  strains . To thisS. aureus as the only isolated species. The incidence of CPS was detected in 100% (20/20) of the breast, 95% (19/20) of the thigh, and 85% (17/20) of both the giblet and fillet samples  were from giblets, 38 (26.6%) from breasts, 33 (23.1%) from thighs, and 28 (19.6%) from fillets (p = 0.1266). Also, there was an insignificant variation between the CPS count in the thigh and breast samples (p = 0.2296). However, there was a significant variation between the CPS count in the fillet and giblet samples at p = 0.0008 and between the fillet and breast samples at p = 0.008.Among the 80 cut-up chicken meat samples tested, 73 (91.3%) were found to be contaminated by  samples . Out of  fillets . The staAs illustrated in S. aureus strains against 11 antimicrobial agents was investigated. As shown in S. aureus strains against CTX was considerably higher in comparison with other antimicrobial agents. The maximum resistance was observed against CTX (70.6%), followed by IMP (66.4%) and PMB (65.7%), GEN (60.1%), ERY (58.7%), SAM and CAF (51%), and CHL (50.3%). The resistance to FA was 42.7%. The resistance to VAN and TET was 34.3% and 31.5%, respectively, as shown in the S. aureus strains showed that out of 143 S. aureus strains, 117 were MDR , while 5  were classified as pan drug resistant strains . The MAR index analysis revealed that all tested strains had a very high MAR index value of more than 0.2  incidence. The obtained data showed that 63.6% (14/22) of the tested strains harbored the aacA-aphD gene, 54.5% (12/22) harbored the mecA gene, and 50% (11/22) harbored the blaZ gene, and confirmed the incidence of MDR in the tested S. aureus strains inhabiting retail raw chicken meat samples. However, the apmA gene (6/22) and vanA gene (5/22) exhibited lower incidence in comparison with the other investigated ARGs (clfA (15/22), tst (11/22), and sea (13/22) exhibited significantly higher incidence in the investigated S. aureus strains in comparison with seb and pvl, which had incidence among the examined S. aureus strains with a percentage of 27.3% (6/22) and 13.6% (3/22), respectively.Out of the 117 identified MDR  pattern  to screeted ARGs . FurtherS. aureus, the phylogenetic tree of the six strains of cluster α (Staphylococcus aureus UP_1097 (CP047803), CPSA-11 showed an identity of 98.15% with Staphylococcus aureus Min-175 (CP086121), and CPSA-18 showed a 99.13% identity to Staphylococcus aureus AATYW (CP116909). CPSA-29 showed a 98.8% identity with Staphylococcus aureus CHU15-080 (CP065871). CPSA-34 and CPSA-47 showed a 98.60 and 9916% identity to Staphylococcus aureus 1549-SCV (LT992435) and Staphylococcus aureus SA 1807 (CP041634), respectively , followed by carvacrol and thymol. Furthermore, the mean MIC values against S. aureus for eugenol and protocatechuic acid were about 6–12 times and 16–24 times higher than hydroquinone  are listed in oquinone . The staS. aureus cells were detected by SEM analysis. S. aureus cells with hydroquinone, which exhibited relatively higher antimicrobial activity compared to other tested phenolic compounds. As observed in S. aureus cells treated with hydroquinone exhibited wrinkled, irregular outer surfaces, along with adhesion, fragmentation, and aggregation of cellular debris and damaged cells. Moreover, these cells displayed non-uniform sizes and distributions. These results indicate that hydroquinone treatment results in damage to S. aureus cells.The morphological changes in As illustrated in S. aureus were carried out following ISO 6888-1:1999/Amd.2:2018 [w/v), and the combination was mixed for 2 min in a stomacher  at 200 rpm. After that, a tenfold serial dilution (10−5–10−8) was prepared using 1 mL of the homogenate, and a volume of 100 µL of each dilution was spread onto Baird Parker agar medium enriched with egg yolk tellurite emulsion . After 48 h of incubation at 37 °C, a morphological characterization was conducted to inspect black or dark grey colonies with halo zones and selected as typical colonies for S. aureus [The morphological and biochemical identification and quantification of d.2:2018  procedur. aureus . Five ty. aureus . For fur. aureus .® 2 system  based on the manufacturer’s instructions. In this study, 11 antimicrobial agents (An AST was conducted using VITEKl agents  were tesS. aureus strains was conducted by polymerase chain reaction (PCR) specific primer pairs of 16S rRNA F 5′-GTAGGTGGCAAGCGTTATCC-3′ and R 5′-CGCACATCAGCGTCAG-3′ to amplify the 16S rRNA gene of S. aureus. PCR programming was begun with an initial denaturation step at 94 °C for 2 min followed by 35 cycles of 94 °C for 30 s, 50 °C for 30 s, and 72 °C for 45 s, ending with a final extension step at 72 °C for 4 min. S. aureus ATCC 25,923 was used as a positive control in this experiment. DNA sequencing was analyzed using a BLAST search (http://www.ncbi.nlm.nih.gov/BLAST/ (accessed on 29 April 2023)). A phylogenetic tree was constructed using MEGA software (V. 6) software.The molecular identification of the selected MDR and virulence blaZ, van, apmA, mecA, and aacA–aphD) and various genes involved in virulence  were investigated by PCR using the listed primers in http://www.ncbi.nlm.nih.gov/blast (accessed on 29 April 2023)). The evolutionary tree was analyzed and built using MEGA 6 software.Antimicrobial resistance genes (ARGs) . Stock solutions were freshly prepared following the method described by Gutiérrez-Larraínzar et al. . BrieflyS. aureus strains according to the ISO Standard (20776-1:2006) [6 CFU/mL.The procedure for performing a microdilution assay to evaluate the MIC values of tested phenolic compounds against pathogenic MDR -1:2006) . After tv/v) and a phenolic compound were used as negative controls. The microplates were sealed using a sterile microporous film, mixed manually, and incubated at 37 °C for 24 h. Afterward, the absorbance (OD620 nm) was detected using a microplate reader . MIC was considered the lowest concentration of the tested material that inhibited the visible growth of the tested strain [The microbial inhibition concentration was examined following the method described by Gutiérrez-Larraínzar et al. . Except d strain . Three tS. aureus cells before and after treatment, SEM analysis was performed. S. aureus was inoculated into Lauria Broth medium (LB) and cultivated at 35 °C for 12 h under shaking conditions. Samples containing S. aureus (107 CFU/mL) in LB, along with the selected antimicrobial agent at the MIC value, were incubated at 35 °C for 9 h. Bacterial cells were harvested by centrifugation at 5000 rpm for 10 min at 4 °C. The control was prepared, as previously mentioned, without the antimicrobial agent. Bacterial cells were fixed for 12 h in 2.5% glutaraldehyde. The fixed bacterial cells were washed three times with a 0.1 M phosphate buffer solution (PBS) for 2 h. Then, the bacterial cells were fixed again for 1.5 h with osmic acid and washed three times for 2 h using double-distilled water. Subsequently, the bacterial cells were dehydrated by two rounds of serial dehydration, in 50%, 70%, 80%, 90%, and 100% alcohol solutions, at 15 min intervals, followed by rinsing in isoamyl acetate for 30 min. Finally, the cells were dried by CO2 critical point drying , mounted, and platinized with an ion sputter coater (IB-5) and observed by SEM .To investigate the morphological changes of t-test was used to compare the variation between groups.The experimental analyses were carried out in triplicate as three independent variables, and the variations observed in the values of each experiment were statistically analyzed using GraphPad Prism version (8.0.2) software. A S. aureus in chicken meat in markets [S. aureus incidence in retail chicken meat might be because of different factors such as slaughtering practices, handling process, geographical location, sampling techniques, and hygienic practices. Consequently, monitoring the incidence of S. aureus in chicken meat products under different conditions is an essential practice to ensure product microbiological quality.The results obtained were consistent with numerous reports stating the high prevalence of  markets ,60,61. W markets  stated t markets  found thS. aureus. Also, Morshdy et al. [In this study, all findings suggest the existence of potential sources  of food contamination. These working conditions could promote the proliferation of microorganisms in places of sale and the contamination of chicken. These results conform to those of Guédé et al.  who claiy et al.  stated ty et al. .S. aureus strains. The strains of the P22 pattern showed a pan drug-resistant phenotype profile . However, the remaining 21 patterns (P1–P21) were MDR. Moreover, all MDR strains exhibited a high incidence of multiple antibiotic resistance (3–11), and ≥50% of the strains showed multiple resistance to ≥6 antibiotics. Enumerating the MAR index is a useful method for health risk assessment and isolates with values >0.2 suggest it is a possible means of contamination that could be categorized as ‘high risk’ [S. aureus strains reveal that S. aureus strains may employ numerous mechanisms of resistance simultaneously and may not always follow the same mode of action or behavior to resist various classes of antibiotics.Antibiogram resistance profiles (ARS) were remarkably varied because a total of 22 patterns (P1–P22) were observed among tested strains. P2 was the most common ARP, which was represented by 15 12.8%) gh risk’ . A MAR i.8% gh riS. aureus strains isolated from chicken meat could be a reservoir of resistance and virulence genes. In this regard, in Nigeria, Igbinosa et al. [Staphylococcus spp. and observed the incidence of MDR S. aureus species. Similar findings were observed in Bangladesh, where 43.5% of S. aureus isolates were Methicillin-resistant S. aureus [blaZ, mecA, and aacA–aphD, tetracycline , and erythromycin (ermB and ermC). Additionally, Al-sherees [aacA/aphD provides resistance to aminoglycosides . The synthesis of β-lactamases, which are expressed by blaZ and can encode the β-lactamase enzyme (penicillinase) which inactivates antibiotics through the hydrolysis of the peptide bond in the β-lactam ring, may be the root cause of S. aureus resistance to penicillin [mecA gene, which encodes a surrogate penicillin-binding protein (PBP2a), may have undergone modification due to penicillin resistance in zoonotic-origin S. aureus strains [S. aureus strains harbored the mecA gene. As a result, sanitary practices should be addressed in Egyptian markets. Liu et al. [cfr gene had been previously found in several Bacillus spp., Enterococcus spp., and Staphylococcus spp, which indicates the transferability of this resistance gene. Tsai et al. [cfr gene is a radical SAM (S-adenosyl-L-methionine). Moreover, the cfr gene’s mechanism is activated by a binding methyl group to the microbial ribosome, which reduces the binding of several antibiotics to the peptidyl transferase core of the microbial ribosomes. However, Bordeleau et al. [apmA is a unique aminoglycoside antibiotic acetyltransferase encoded gene that produces a 274 amino acid protein that results in resistance to chloramphenicol and/or streptogramin.Various diseases could be successfully treated after developing reliable antimicrobial agents in the 1940s. Still, in recent years, this has become much more challenging because of the organisms’ propensity to develop resistance to the antimicrobials commonly used in medical or industrial applications . In thisa et al.  found tha et al.  reported. aureus . Further. aureus  stated t-sherees  reportednicillin . Additio strains ,15. MRSAu et al.  stated ti et al.  also repu et al.  found thS. aureus may generate a wide range of enterotoxins, the exotoxin-encoding genes (sea and seb) are thought to be responsible for 95% of cases of food poisoning [S. aureus usually causes recurrent skin and soft tissue infections. PVL binds to and kills human neutrophils, causing neutrophil extracellular traps to develop. However, the pathomechanism has yet to be well investigated. In addition to being heat-resistant water-soluble proteins, staphylococcal enterotoxins also maintain their proteolytic resistance properties after ingestion [clfA) is required for endocarditis and arthritis and is a reason for S. aureus cells’ development in the bloodstream (platelets and plasma) [tst, and results in a variety of severe clinical disorders, including Kawasaki syndrome [S. aureus might be a factor in developing a more severe immune response syndrome. The emergence and spread of antibiotic resistance are still being tested as options for zoonotic infections by pathogenic S. aureus strains.While oisoning . It is koisoning ,75. Alsooisoning  stated tngestion . Staphyl plasma) . TSST-1 syndrome . Pérez esyndrome  reportedS. aureus. Hydroquinone emerged as the most potent agent compared with other tested compounds, i.e., carvacrol and thymol demonstrated comparatively lower effectiveness in their inhibitory activity against S. aureus. In this regard, Rúa et al. [S. aureus, outperforming butylated hydroxyanisole in all aspects. This dual capability might lower the total quantity of meal additives, resulting in more natural products. Gallic acid and hydroquinone, two other phenolic compounds employed as aromatizants in the European Union, are likewise efficient antimicrobials against S. aureus and have antioxidant activity. Similar findings were reported by Gutiérrez-Larraínzar et al. [S. aureus .The present study revealed a significant variation in the ability of different phenolic compounds to inhibit a et al.  reportedr et al.  who statr et al.  reportedS. aureus strains. Hydroquinone had a high MIC value  for some strains, with an average of 54 μg/mL, and showed an antibacterial effect against all tested strains, potentially inhibiting the growth of all pathogenic MDR strains. This effectiveness could be because of the different mechanisms of hydroquinone, which are related to its chemical structure .Generally, hydroquinone showed potential antibacterial activity compared with other tested natural antimicrobial agents  against pathogenic MDR tructure A and abia et al.  recentlyS. aureus strains isolated from retail raw chicken samples in this study. Although bacterial cells possess a sophisticated multilayered structure that protects them from external stimuli, phenolics may directly attach to and adversely impact their cell membranes. The intricacy of the cell membrane helps bacteria not only survive but also transport nutrients and waste. Gram-positive bacteria are the most susceptible to phenolic chemicals due to the presence of peptidoglycans on their surface and the lack of an outer membrane [S. aureus (Gram-positive) compared to E. coli (Gram-negative) strains.The antibacterial mechanism demonstrated that hydroquinone might degrade the bacterial cell wall and membrane, disrupt protein synthesis, cause intracellular substance leakage, enhance permeability, change gene expression, and inhibit enzymatic activity, as shown in membrane . In lineS. aureus cells using ɛ-poly-lysine and found that the control S. aureus cell appeared equal in size and distribution, smooth, and rounded. However, S. aureus cells treated with antimicrobial agents exhibited wrinkled and irregular surfaces, accompanied by the aggregation of dead bacterial cells in SEM analysis. These morphological changes can be attributed to the bioactivity of hydroquinone on the bacterial cell wall and membrane, which leads to an increase in the cellular permeability and leakage of the cytoplasmic contents. Moreover, hydroquinone can alter protein synthesis and influence the expression of genes, causing a lethal effect on bacterial cells [At this level, various reactions occur due to the presence of functional groups in the cell membrane. For example, phenolics can negatively impact the bacterial cell wall by interacting with the hydroxyl groups (-OH) that interact with the peptidoglycans in the cell membrane. The phenolic compound type and the bacterium’s type determine the bacterial resistance to this sort of antibacterial action. Unlike Gram-positive bacteria, Gram-negative bacteria have three cell membrane layers, all of which are resistant to the antibacterial action of phenolic compounds. The high number of phospholipids on the lipophilic outer membrane is linked to this resistance . In thisal cells .S. aureus compared to other examined phenolic substances containing two and one OH group. With respect to protocatechuic acid, the obtained data show that its antibacterial effectiveness is inversely related to its structure (number of OH groups). Notably, the impact of the OH groups may be less important for S. aureus, suggesting that this compound could employ a multitargeted action mechanism. However, Hirakawa and Sano [2O2), which induces hydroquinone antimicrobial activity, possibly through concentration-dependent hydrogen peroxide synthesis. Hydroquinone lacks the ability to directly alter the integrity of bacterial DNA on its own. The H2O2 synthesis process can alter the bacterial proteins’ expression, resulting in DNA impairment and aberrant transcription [Hydroquinone also affects the production and control of DNA in bacteria. Its structure comprises an aromatic ring and hydroxyl groups which enable hydroquinone to interact with the carboxylic or amino groups found in proteins . Becauseand Sano  proposedcription . This obAdditionally, Zhang et al.  reportedS. aureus strains in contrast to the tested phenolic compounds, in particular, hydroquinone, which can affect various microbial organelles. Consequently, this study strongly recommends performing further investigations and experimental studies to comprehensively understand the mechanisms underlying the potential use of phenolic compounds as alternatives to conventional antimicrobial agents.These diverse mechanisms by which phenolic compounds, such as hydroquinone, combat bacterial pathogens may indicate the ability of phenolic compounds and give these compounds potential advantages over conventional antimicrobial agents. The MAR index  indicateS. aureus incidence in raw retail chicken meat in the Egyptian market which can cause FBDs. These pathogens may contribute to common FBDs in Egypt. The antibiotic resistance and pathogenicity were assessed and exhibited severe problems for food industrial applications and quality control. The application of natural compounds as antimicrobial therapy is an expanding field of study in reference to developing a promising technology to combat food containing MDR pathogens. Hydroquinone showed outstanding activity against zoonotic-resistant and virulent S. aureus strains. Our findings provide scientific proof of hydroquinone implementation in food safety applications. Hence, hydroquinone applications as a food additive can also serve the industrial application field with particular reference to the inhibition of zoonotic and pathogenic MDR S. aureus strains. Therefore, this study suggests initiatives to enhance sanitary standards in Egyptian markets, particularly in traditional markets with higher contamination rates.The obtained data in this study revealed a high


Staphylococcus aureus which perpetuates the inflammatory reaction. Treatments for AD should help to restore microbial diversity in the skin and intestine, as well as epithelial barrier function. Pre-clinical models have shown that PPAR-γ agonists can suppress Th17 responses, IgE production and mast cell function, while improving the epidermal barrier and microbial homeostasis. Overall, PPAR-γ agonists may be effective in a subset of patients with AD, and future studies should distinguish their metabolic and anti-inflammatory effects in order to inform the best therapies.Atopic dermatitis (AD) is an inflammatory skin disease characterized by epidermal barrier disruption, Th2 immune responses to skin allergens and microbial dysbiosis within affected lesions. Studies within the past decade have revealed genetic and environmental factors contributing to AD in children. Obesity is a metabolic disorder that often manifests early in life and is associated with reduced bacterial diversity, leading to skin colonization with lipophilic bacteria and intestinal colonization with pro-inflammatory species. These changes impair epithelial barriers and promote Th17 responses, which may worsen the severity of AD symptoms. While few studies have examined the contribution of microbiota in obesity-induced allergies, there is emerging evidence that PPAR-γ may be an effective therapeutic target. This review discusses the microbiome in pediatric AD, treatment with probiotics, how disease is altered by obesity and potential therapeutic effects of PPAR-γ agonists. While healthy skin contains diverse species adapted for specific niches, lesional skin is highly colonized with  Atopic march describes the successive development of allergic diseases beginning in infancy, including atopic dermatitis (AD), allergic rhinitis, asthma and food allergy . The firEpithelial surfaces of the body are colonized with microorganisms, collectively referred to as the microbiome. Many studies have characterized bacterial and fungal species present in the gastrointestinal (GI) tract, skin and lungs in healthy and diseased individuals, revealing several immunomodulatory functions. Nevertheless, our molecular understanding of how microbial colonization impacts the immune system is incomplete. Beneficial and detrimental roles for microbes have been identified in pediatric allergies, with protection associated with breastfeeding, vaginal delivery, having pets and avoiding antibiotics . CollectObesity is a metabolic disorder that often manifests early in life and is associated with reduced bacterial diversity in the GI tract –6. SeverIL13, IL17A, IL17F, IL22, CCL17 and S100s , or eczema, is a chronic, relapsing inflammatory skin disease with a prevalence of up to 25% in children and 7% in adults . Symptomnd S100s . During Obese patients with immunologic diseases including atopy and asthma have more severe disease than their lean counterparts , 12. StuCutibacterium, Malassezia, Staphylococcus and Corynebacterium . Th. ThCutibanguinis . In addicomycota . Increas Candida , 22. ThuMalassezia spp. are lipophilic and can induce Th17 responses  correlated with an increased Shannon Diversity Index compared to normal weight or obese individuals . Ten genesponses , which mStreptococcus, Cutibacterium and Malassezia, accompanied by increases in Staphylococcus aureus, suggesting an antagonistic relationship between skin commensals -deficiency contributes to dysbiosis by increasing skin pH, facilitating colonization with . aureus . Virulenllergens . Skin micus spp. . In thisdulthood , suggest2, TTC27 , althougS. cohnii protected against spontaneous and chemical-induced AD by suppressing inflammation (S. cohnii strain-specific differences were observed. Roseomonas and Cutibacterium spp. may inhibit colonization with S. aureus and be suitable probiotics for AD skin (Cutibacterium spp. (C. acnes) also facilitate S. aureus biofilm formation. A probiotic formulation containing Roseomonas mucosa, poly(vinyl pyrrolidione), poly and sodium alginate demonstrated antimicrobial activity against S. aureus  rosiglitazone alleviated AD in response to a high fat diet, demonstrating a critical function for PPAR-γ . In this17 cells . Topicalysbiosis . Furtherysbiosis –83. The ysbiosis , facilitysbiosis , mast ceysbiosis , 87, andysbiosis , demonstysbiosis .Corynebacteria spp. rather than S. aureus (The etiology and pathophysiology of psoriasis bears some similarities with AD, including obesity, microbial dysbiosis and Th17-mediated inflammation . Clinica. aureus . Further. aureus . Other a. aureus , 94. Alt. aureus , 96, sugA surge of studies from the last decade helped to define the commensal microbiome in pediatric AD and how dysbiosis contributes to chronic diseases. Recent findings into the pathophysiology of obesity-driven AD have revealed PPAR-γ to be a potential therapeutic target. Future studies examining the efficacy of PPAR-γ modulators should distinguish their metabolic vs. anti-inflammatory effects in the gut, skin, adipose tissue and immune system, in order to inform the best therapies. The severity of AD and its role in initiating atopic march underscore the significance of utilizing effective treatments which may help to reduce the risk of asthma later in life.