{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:28:07Z","timestamp":1790094487273,"version":"4.0.1"},"reference-count":58,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"County-School Cooperation Project in Suichang County, China","award":["2024-HZ12"],"award-info":[{"award-number":["2024-HZ12"]}]},{"name":"Ecological Discipline Construction Fund of Lishui University, China","award":["2024-HZ12"],"award-info":[{"award-number":["2024-HZ12"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>The intestinal microbiota regulates host metabolic homeostasis through production of bioactive microbial metabolites. These microorganisms facilitate digestion, enhance immune function, maintain osmoregulation, and support physiological balance via these bioactive compounds, thereby enhancing environmental adaptation. Our study investigated intestinal microbiota\u2013liver metabolic interactions in Leptobrachium liui using 16S rRNA gene sequencing and non-targeted liquid chromatography\u2013tandem mass spectrometry metabolomics. Key findings include (1) comparable alpha diversity but distinct microbial community structures between the small intestine (SI) and large intestine (LI), with the SI dominated by Enterobacteriaceae (72.14%) and the LI by Chitinophagaceae (55.16%); (2) segment-specific microbe\u2013metabolite correlations, with predominantly positive correlations in the SI and complex patterns in the LI involving fatty acids, amino acids, and energy metabolites; and (3) significant correlations between specific bacterial families (Aeromonadaceae, Enterobacteriaceae, Chitinophagaceae) and hepatic metabolites related to fatty acid metabolism, amino acid synthesis, and energy pathways, indicating potential gut\u2013liver axis associations. These findings provide insights into amphibian intestinal microbiota\u2013hepatic metabolite associations and may inform future studies of host\u2013microbe interactions.<\/jats:p>","DOI":"10.3390\/ani15131973","type":"journal-article","created":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T11:20:11Z","timestamp":1751628011000},"page":"1973","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Integrated Microbiome\u2013Metabolome Analysis Reveals Intestine\u2013Liver Metabolic Associations in the Moustache Toad"],"prefix":"10.3390","volume":"15","author":[{"given":"Shui-Sheng","family":"Yu","sequence":"first","affiliation":[{"name":"Laboratory of Amphibian Diversity Investigation, College of Ecology, Lishui University, Lishui 323000, China"},{"name":"Administration Center of Zhejiang Jiulongshan National Nature Reserve, Suichang, Lishui 323312, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Wen","family":"Xiang","sequence":"additional","affiliation":[{"name":"Laboratory of Amphibian Diversity Investigation, College of Ecology, Lishui University, Lishui 323000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9295-1684","authenticated-orcid":false,"given":"Lin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hubei Shizhen Laboratory, School of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Hua","family":"Guo","sequence":"additional","affiliation":[{"name":"Ecological Forestry Development Center, Suichang, Lishui 323300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Administration Center of Zhejiang Jiulongshan National Nature Reserve, Suichang, Lishui 323312, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2484-5855","authenticated-orcid":false,"given":"Guo-Hua","family":"Ding","sequence":"additional","affiliation":[{"name":"Laboratory of Amphibian Diversity Investigation, College of Ecology, Lishui University, Lishui 323000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua-Li","family":"Hu","sequence":"additional","affiliation":[{"name":"Administration Center of Zhejiang Jiulongshan National Nature Reserve, Suichang, Lishui 323312, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4456","DOI":"10.1016\/j.csbj.2023.08.030","article-title":"Stability of human gut microbiome: Comparison of ecological modelling and observational approaches","volume":"21","author":"Akulinin","year":"2023","journal-title":"Comput. Struct. Biotec."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/nri.2016.42","article-title":"Gut microbiota, metabolites and host immunity","volume":"16","author":"Rooks","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1186\/s12964-023-01219-9","article-title":"Short-chain fatty acids in diseases","volume":"21","author":"Zhang","year":"2023","journal-title":"Cell Commun. Signal."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.chom.2015.03.005","article-title":"Crosstalk between microbiota-derived short-chain fatty acids and intestinal epithelial HIF augments tissue barrier function","volume":"17","author":"Kelly","year":"2015","journal-title":"Cell Host Microbe"},{"key":"ref_5","first-page":"21","article-title":"The role of the gut microbiota in bile acid metabolism","volume":"16","year":"2018","journal-title":"Ann. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"403","DOI":"10.4062\/biomolther.2024.009","article-title":"Gut microbiota metabolite messengers in brain function and pathology at a view of cell type-based receptor and enzyme reaction","volume":"32","author":"Lee","year":"2024","journal-title":"Biomol. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.bbr.2014.07.027","article-title":"Serotonin, tryptophan metabolism and the brain-gut-microbiome axis","volume":"277","author":"Clarke","year":"2015","journal-title":"Behav. Brain Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"16079","DOI":"10.3748\/wjg.v20.i43.16079","article-title":"Gut microbiota and metabolic syndrome","volume":"20","author":"Festi","year":"2014","journal-title":"World J. Gastroentero."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"733992","DOI":"10.3389\/fcimb.2022.733992","article-title":"The gut microbiota in inflammatory bowel disease. Front","volume":"12","author":"Qiu","year":"2022","journal-title":"Cell. Infect. Mi."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1111\/1751-7915.13524","article-title":"The gut microbiota and its interactions with cardiovascular disease","volume":"13","author":"Xu","year":"2020","journal-title":"Microb. Biotechnol."},{"key":"ref_11","first-page":"1463","article-title":"Regulation of intestinal barrier function by microbial metabolites","volume":"11","author":"Ghosh","year":"2021","journal-title":"Cell. Mol. Gastroenter."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1016\/j.cell.2019.08.010","article-title":"Antibiotics-driven gut microbiome perturbation alters immunity to vaccines in humans","volume":"178","author":"Hagan","year":"2019","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s11154-019-09512-0","article-title":"Dietary lipids, gut microbiota and lipid metabolism","volume":"20","author":"Schoeler","year":"2019","journal-title":"Rev. Endocr. Metab. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1017\/S0029665120006916","article-title":"SCFA: Mechanisms and functional importance in the gut","volume":"80","author":"Marinelli","year":"2021","journal-title":"Proc. Nutr. Soc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1126\/science.aaw3134","article-title":"The intestinal microbiota programs diurnal rhythms in host metabolism through histone deacetylase 3","volume":"365","author":"Kuang","year":"2019","journal-title":"Science"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/s41569-018-0108-7","article-title":"Dietary metabolism, the gut microbiome, and heart failure","volume":"16","author":"Tang","year":"2019","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/nm.4517","article-title":"Current understanding of the human microbiome","volume":"24","author":"Gilbert","year":"2018","journal-title":"Nat. Med."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Rastogi, S., Mohanty, S., Sharma, S., and Tripathi, P. (2022). Possible role of gut microbes and host\u2019s immune response in gut\u2013lung homeostasis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.954339"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.18203\/2319-2003.ijbcp20184211","article-title":"The role of liver in metabolism: An updated review with physiological emphasis","volume":"7","author":"Alamri","year":"2018","journal-title":"Int. J. Basic Clin. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1016\/j.cmet.2022.09.017","article-title":"Gut-liver axis: Pathophysiological concepts and clinical implications","volume":"34","author":"Tilg","year":"2022","journal-title":"Cell Metab."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Zhu, M., Xie, R.S., Xu, L.Y., Xu, Y.G., Luo, H.M., and Lan, X.T. (2024). The gut-liver axis in fatty liver disease: Role played by natural products. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1365294"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/s41579-023-00904-3","article-title":"The gut\u2013liver axis and gut microbiota in health and liver disease","volume":"21","author":"Hsu","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1146\/annurev-environ-102014-021358","article-title":"State of the world\u2019s amphibians","volume":"40","author":"Catenazzi","year":"2015","journal-title":"Annu. Rev. Environ. Resour."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/s41586-023-06578-4","article-title":"Ongoing declines for the world\u2019s amphibians in the face of emerging threats","volume":"622","author":"Luedtke","year":"2023","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Santos, B., Martins, F.M., Sabino-Pinto, J., Licata, F., and Crottini, A. (2023). Skin and gut microbiomes of tadpoles vary differently with host and water environment: A short-term experiment using 16S metabarcoding. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-43340-2"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"wrad009","DOI":"10.1093\/ismejo\/wrad009","article-title":"Gut microbiota reflect adaptation of cave-dwelling tadpoles to resource scarcity","volume":"18","author":"Zhu","year":"2024","journal-title":"ISME J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1111\/1749-4877.12749","article-title":"The intestinal microbiota and metabolic profiles of Strauchbufo raddei underwent adaptive changes during hibernation","volume":"19","author":"Cao","year":"2024","journal-title":"Integr. Zool."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"13699","DOI":"10.1038\/ncomms13699","article-title":"Amphibian gut microbiota shifts differentially in community structure but converges on habitat-specific predicted functions","volume":"7","author":"Bletz","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.scitotenv.2020.140142","article-title":"Environmental and host factors shaping the gut microbiota diversity of brown frog Rana dybowskii","volume":"741","author":"Tong","year":"2020","journal-title":"Sci. Total Environ."},{"key":"ref_30","unstructured":"Fei, L., and Ye, C.Y. (2016). Amphibians of China, Science Press."},{"key":"ref_31","first-page":"14","article-title":"The classification of the Leptobrachium species in Jiulong Mountain, Zhejiang Province is discussed from the perspective of its horny black spines","volume":"14","author":"Huang","year":"1984","journal-title":"J. Hangzhou Norm. Univ. Nat. Sci."},{"key":"ref_32","first-page":"22","article-title":"The Chong\u2019an moustache toad in Jiulong Mountain, Zhejiang Province","volume":"6","author":"Liu","year":"1987","journal-title":"Chin. J. Wildl."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/j.ympev.2007.09.019","article-title":"A phylogenetic analysis of the frog genera Vibrissaphora and Leptobrachium, and the correlated evolution of nuptial spine and reversed sexual size dimorphism","volume":"46","author":"Zheng","year":"2008","journal-title":"Mol. Phylogenet. Evol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Zhou, Q., Xiang, H.M., Zhang, M.Y., Liu, Y., Gu, Z.R., Lan, X.Y., Wang, J.X., and Jiang, W.S. (2023). Two complete mitochondrial genomes of Leptobrachium (Anura: Megophryidae: Leptobrachiinae): Characteristics, population divergences, and phylogenetic implications. Genes, 14.","DOI":"10.3390\/genes14030768"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5588","DOI":"10.11646\/zootaxa.4732.4.8","article-title":"The advertisement call of the moustache toad Leptobrachium liui Pope, 1947 (Anura: Megophryidae) from eastern China","volume":"4732","author":"Ding","year":"2020","journal-title":"Zootaxa"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"192","DOI":"10.3724\/ahr.2095-0357.2024.0045","article-title":"Environmental and morphological determinants of advertisement call variability in a moustache toad","volume":"16","author":"Hu","year":"2025","journal-title":"Asian Herpetol. Res."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Zhang, C.Y., Hu, H.L., Wang, Y., Zhang, L., and Ding, G.H. (2024). Combined effects of thermal environment and gene regulation on metabolic enzyme activities of major metabolic tissues in a winter-breeding amphibian. J. Therm. Biol., 125.","DOI":"10.1016\/j.jtherbio.2024.104000"},{"key":"ref_38","unstructured":"Core Team (2023). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Wickham, H. (2016). ggplot2: Elegant Graphics for Data Analysis, Springer.","DOI":"10.1007\/978-3-319-24277-4_9"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.eng.2022.12.011","article-title":"The fish microbiota: Research progress and potential applications","volume":"29","author":"Luan","year":"2023","journal-title":"Engineering"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1016\/j.chom.2023.07.008","article-title":"Symbiotic Firmicutes establish mutualism with the host via innate tolerance and resistance to control systemic immunity","volume":"31","author":"Jordan","year":"2023","journal-title":"Cell Host Microbe"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"112471","DOI":"10.1016\/j.ecoenv.2021.112471","article-title":"Ammonia stress influences intestinal histomorphology, immune status and microbiota of Chinese striped-neck turtle (Mauremys sinensis)","volume":"222","author":"Khan","year":"2021","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1053\/j.gastro.2022.10.018","article-title":"Gut microbiota modulation of efficacy and toxicity of cancer chemotherapy and immunotherapy","volume":"164","author":"Chrysostomou","year":"2023","journal-title":"Gastroenterology"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Brenes-Soto, A., Dierenfeld, E.S., and Janssens, G.P. (2018). The interplay between voluntary food intake, dietary carbohydrate-lipid ratio and nutrient metabolism in an amphibian, (Xenopus laevis). PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0208445"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Yang, K., Li, G., Li, Q., Wang, W., Zhao, X., Shao, N., Qiu, H., Liu, J., Xu, L., and Zhao, J. (2025). Distribution of gut microbiota across intestinal segments and their impact on human physiological and pathological processes. Cell Biosci., 15.","DOI":"10.1186\/s13578-025-01385-y"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1089\/can.2019.0014","article-title":"Effects of oleamide on the vasomotor responses in the rat","volume":"5","author":"Mascher","year":"2020","journal-title":"Cannabis Cannabinoid"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1840765","DOI":"10.1080\/19490976.2020.1840765","article-title":"Altered gut bacterial and metabolic signatures and their interaction in gestational diabetes mellitus","volume":"12","author":"Wang","year":"2020","journal-title":"Gut Microbes"},{"key":"ref_48","first-page":"1668","article-title":"Potential role of microRNAs in response to Aeromonas infection in fish","volume":"78","author":"Sadeghi","year":"2023","journal-title":"Arch. Razi Inst."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Casta\u00f1o-Rodr\u00edguez, N., Goh, K., Fock, K.M., Mitchell, H.M., and Kaakoush, N.O. (2017). Dysbiosis of the microbiome in gastric carcinogenesis. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-16289-2"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Liang, P., Ma, Y.N., Yang, L.Y., Mao, L.S., Sun, Q., Sun, C.Z., Liu, Z.J., Mazhar, M., Yang, S.J., and Ren, W. (2022). Uncovering the mechanisms of active components from toad venom against hepatocellular carcinoma using untargeted metabolomics. Molecules, 27.","DOI":"10.3390\/molecules27227758"},{"key":"ref_51","first-page":"1128","article-title":"Whole-genome sequence of Filimonas lacunae, a bacterium of the family Chitinophagaceae characterized by marked colony growth under a high-CO2 atmosphere","volume":"4","author":"Takano","year":"2016","journal-title":"Genome Announc."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/s41579-019-0278-2","article-title":"The pan-immune system of bacteria: Antiviral defence as a community resource","volume":"18","author":"Bernheim","year":"2020","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-Bravo, A., and Figueras, M.J. (2020). An update on the genus Aeromonas: Taxonomy, epidemiology, and pathogenicity. Microorganisms, 8.","DOI":"10.3390\/microorganisms8010129"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1080\/14756366.2017.1350658","article-title":"New sulfurated derivatives of cinnamic acids and rosmaricine as inhibitors of STAT3 and NF-\u03baB transcription factors","volume":"32","author":"Gabriele","year":"2017","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Zhang, X.J., Tao, F.Y., Cui, T., Luo, C., Zhou, Z.G., Huang, Y.C., Tan, L.L., Peng, W., and Wu, C.J. (2022). Sources, transformations, syntheses, and bioactivities of monoterpene pyridine alkaloids and cyclopenta [c] pyridine derivatives. Molecules, 27.","DOI":"10.3390\/molecules27217187"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"113436","DOI":"10.1016\/j.jep.2020.113436","article-title":"Dingxin Recipe IV attenuates atherosclerosis by regulating lipid metabolism through LXR-\u03b1\/SREBP1 pathway and modulating the gut microbiota in ApoE-\/-mice fed with HFD","volume":"266","author":"Zhang","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Chen, Q., Zhou, T., Yuan, J.J., Xiong, X.Y., Liu, X.H., Qiu, Z.M., Hu, L.L., Lu, H., He, Q., and Liu, C. (2023). Metabolomics profiling to characterize cerebral ischemia-reperfusion injury in mice. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1091616"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Ye, X.W., Pi, X.G., Zheng, W.X., Cen, Y.X., Ni, J.H., Xu, L.Y., Wu, K.F., Liu, W., and Li, L.J. (2022). The methanol extract of Polygonatum odoratum ameliorates colitis by improving intestinal short-chain fatty acids and gas production to regulate microbiota dysbiosis in mice. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.899421"}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/15\/13\/1973\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:04:42Z","timestamp":1760033082000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/15\/13\/1973"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,4]]},"references-count":58,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["ani15131973"],"URL":"https:\/\/doi.org\/10.3390\/ani15131973","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,4]]}}}