{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T08:27:48Z","timestamp":1787646468832,"version":"build-2736575974"},"reference-count":70,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Gut-derived indole metabolites are implicated in the gut\u2013kidney axis, but the factors controlling the intestinal conversion of indole-3-acetic acid (IAA) to skatole remain incompletely defined. We developed a deterministic, hypothesis-generating framework that represents this conversion as a finite-pool allocation process governed by pH-dependent ecological permissiveness, terminal-conversion capacity, precursor availability, spatial progression, and competing loss. The model separates the available-pool scale from a dimensionless integrated conversion exposure, \u03a8. Across 5400 loss-free scenarios spanning 10 pH profiles and graded metabolic and host-associated constraints, the distal endpoint normalized to the available pool followed the analytically derived relationship 1\u2212exp\u2212\u03a8. Thus, distinct combinations of mechanistically relevant parameters produced the same normalized distal endpoint, demonstrating that this endpoint alone cannot uniquely identify the underlying mechanism. Competing loss further separated absolute, total-pool-normalized, and conditional outputs, showing that mechanistic interpretation depends on endpoint normalization. Analytical and numerical checks supported internal consistency. The framework was not fitted to biological data, and concentration values were used only as technical scaling references. This biologically unvalidated model generates experimentally testable hypotheses regarding the roles of pH, terminal-conversion capacity, precursor availability, and competing loss in intestinal IAA-to-skatole metabolism; it is not intended to provide physiological or clinical predictions.<\/jats:p>","DOI":"10.3390\/toxins18090362","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T14:49:34Z","timestamp":1787582974000},"page":"362","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Upstream Ecological Control of the IAA\u2013Skatole Branch: A pH-Dependent Triple-Lock Framework for Gut-Derived Uremic Toxin Precursors"],"prefix":"10.3390","volume":"18","author":[{"given":"Kana","family":"Yuasa","sequence":"first","affiliation":[{"name":"Graduate School of Natural Science and Technology, Shimane University, 1060 Nishikawatsu-Cho, Matsue 690-8504, Shimane, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0939-0098","authenticated-orcid":false,"given":"Hidehisa","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Graduate School of Natural Science and Technology, Shimane University, 1060 Nishikawatsu-Cho, Matsue 690-8504, Shimane, Japan"},{"name":"Faculty of Life and Environmental Sciences, Shimane University, 1060 Nishikawatsu-Cho, Matsue 690-8504, Shimane, Japan"},{"name":"Institute of Agricultural and Life Sciences, Academic Assembly, Shimane University, 1060 Nishikawatsu-Cho, Matsue 690-8504, Shimane, Japan"},{"name":"The United Graduate School of Agricultural Sciences, Tottori University, 4-101 Koyama-Minami, Tottori 680-8553, Tottori, Japan"},{"name":"Estuary Research Center, Shimane University, 1060 Nishikawatsu-Cho, Matsue 690-8504, Shimane, Japan"},{"name":"Interdisciplinary Center for Science Research, Shimane University, 1060 Nishikawatsu-Cho, Matsue 690-8504, Shimane, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"ref_1","unstructured":"GBD 2023 Chronic Kidney Disease Collaborators (2025). Global, regional, and national burden of chronic kidney disease in adults, 1990\u20132023, and its attributable risk factors: A systematic analysis for the Global Burden of Disease Study 2023. Lancet, 406, 2461\u20132482."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"111784","DOI":"10.1016\/j.cbi.2025.111784","article-title":"Oxidative stress and inflammation in renal fibrosis: Novel molecular mechanisms and therapeutic targets","volume":"421","author":"Liu","year":"2025","journal-title":"Chem. Biol. Interact."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Patera, F., Gatticchi, L., Cellini, B., Chiasserini, D., and Reboldi, G. (2024). Kidney Fibrosis and Oxidative Stress: From Molecular Pathways to New Pharmacological Opportunities. Biomolecules, 14.","DOI":"10.3390\/biom14010137"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/s41581-025-00988-5","article-title":"Microbiota and kidney disease: The road ahead","volume":"21","author":"Bloom","year":"2025","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/s41581-022-00647-z","article-title":"Gut microbiome studies in CKD: Opportunities, pitfalls and therapeutic potential","volume":"19","author":"Krukowski","year":"2023","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1038\/s41564-026-02259-w","article-title":"Host factors dictate gut microbiome alterations in chronic kidney disease more strongly than kidney function","volume":"11","author":"Krukowski","year":"2026","journal-title":"Nat. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1016\/j.kint.2020.01.028","article-title":"Gut microbiota generation of protein-bound uremic toxins and related metabolites is not altered at different stages of chronic kidney disease","volume":"97","author":"Gryp","year":"2020","journal-title":"Kidney Int."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Steenbeke, M., Valkenburg, S., Gryp, T., Van Biesen, W., Delanghe, J.R., Speeckaert, M.M., and Glorieux, G. (2021). Gut Microbiota and Their Derived Metabolites, a Search for Potential Targets to Limit Accumulation of Protein-Bound Uremic Toxins in Chronic Kidney Disease. Toxins, 13.","DOI":"10.3390\/toxins13110809"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Gryp, T., Huys, G.R.B., Joossens, M., Van Biesen, W., Glorieux, G., and Vaneechoutte, M. (2020). Isolation and Quantification of Uremic Toxin Precursor-Generating Gut Bacteria in Chronic Kidney Disease Patients. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21061986"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1681\/ASN.2011121175","article-title":"Normal and pathologic concentrations of uremic toxins","volume":"23","author":"Duranton","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.2215\/CJN.03980609","article-title":"Serum indoxyl sulfate is associated with vascular disease and mortality in chronic kidney disease patients","volume":"4","author":"Barreto","year":"2009","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"934","DOI":"10.3390\/toxins6030934","article-title":"The aryl hydrocarbon receptor-activating effect of uremic toxins from tryptophan metabolism: A new concept to understand cardiovascular complications of chronic kidney disease","volume":"6","author":"Dou","year":"2014","journal-title":"Toxins"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/j.kint.2017.11.010","article-title":"Aryl hydrocarbon receptor is activated in patients and mice with chronic kidney disease","volume":"93","author":"Dou","year":"2018","journal-title":"Kidney Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1681\/ASN.2014121241","article-title":"The Aryl Hydrocarbon Receptor is a Critical Regulator of Tissue Factor Stability and an Antithrombotic Target in Uremia","volume":"27","author":"Shivanna","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e2402066","DOI":"10.1002\/advs.202402066","article-title":"Uremic Toxin Receptor AhR Facilitates Renal Senescence and Fibrosis via Suppressing Mitochondrial Biogenesis","volume":"11","author":"Xie","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3294","DOI":"10.1038\/s41467-018-05470-4","article-title":"Microbial tryptophan catabolites in health and disease","volume":"9","author":"Roager","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/j.chom.2018.05.003","article-title":"Gut microbiota regulation of tryptophan metabolism in health and disease","volume":"23","author":"Agus","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1124\/dmd.115.064246","article-title":"Indole and Tryptophan Metabolism: Endogenous and Dietary Routes to Ah Receptor Activation","volume":"43","author":"Hubbard","year":"2015","journal-title":"Drug Metab. Dispos."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.immuni.2013.08.003","article-title":"Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22","volume":"39","author":"Zelante","year":"2013","journal-title":"Immunity"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1038\/nm.4102","article-title":"CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands","volume":"22","author":"Lamas","year":"2016","journal-title":"Nat. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/j.celrep.2018.03.109","article-title":"Gut Microbiota-Derived Tryptophan Metabolites Modulate Inflammatory Response in Hepatocytes and Macrophages","volume":"23","author":"Krishnan","year":"2018","journal-title":"Cell Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1073\/pnas.0906112107","article-title":"The bacterial signal indole increases epithelial-cell tight-junction resistance and attenuates indicators of inflammation","volume":"107","author":"Bansal","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.immuni.2014.06.014","article-title":"Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4","volume":"41","author":"Venkatesh","year":"2014","journal-title":"Immunity"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.chom.2017.06.007","article-title":"Indoleacrylic Acid Produced by Commensal Peptostreptococcus Species Suppresses Inflammation","volume":"22","author":"Wlodarska","year":"2017","journal-title":"Cell Host Microbe"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7173","DOI":"10.3748\/wjg.v26.i45.7173","article-title":"Alteration of fecal tryptophan metabolism correlates with shifted microbiota and may be involved in pathogenesis of colorectal cancer","volume":"26","author":"Sun","year":"2020","journal-title":"World J. Gastroenterol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1093\/bbb\/zbad055","article-title":"Activation of the TLR4-JNK but not the TLR4-ERK pathway induced by indole-3-acetic acid exerts anti-proliferative effects on Caco-2 cells","volume":"87","author":"Tomii","year":"2023","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Takei, C., and Shimizu, H. (2026). Indole-3-Acetic Acid as a Putative Selective AhR Modulator Counteracts Skatole-Induced Dual-Hit Toxicity in Colorectal Cancer Cells. Toxins, 18.","DOI":"10.3390\/toxins18020098"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Naito, K., Tomii, A., Ishii, K., and Shimizu, H. (2026). Indole-3-Acetic Acid and Skatole Exert Opposing Effects on MDR1 Proteostasis in Human Colonic Epithelial Cells: A Molecular Basis for the Gut Microbial Metabolic Switch. J. Xenobiot., 16.","DOI":"10.3390\/jox16010036"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Tomii, A., Takei, C., Yoshikiyo, K., and Shimizu, H. (2025). The Gut Microbial Metabolite Indole-3-Acetic Acid Reprograms Systemic Homeostasis and Ameliorates IBD-Associated Cachexia Independent of Food Intake. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262311260"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.bbrc.2019.01.122","article-title":"Skatole regulates intestinal epithelial cellular functions through activating aryl hydrocarbon receptors and p38","volume":"510","author":"Kurata","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1093\/bbb\/zbad030","article-title":"Skatole-induced p38 and JNK activation coordinately upregulates, whereas AhR activation partially attenuates TNF\u03b1 expression in intestinal epithelial cells","volume":"87","author":"Kurata","year":"2023","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ishii, K., Naito, K., Tanaka, D., Koto, Y., Kurata, K., and Shimizu, H. (2024). Molecular Mechanisms of Skatole-Induced Inflammatory Responses in Intestinal Epithelial Caco-2 Cells: Implications for Colorectal Cancer and Inflammatory Bowel Disease. Cells, 13.","DOI":"10.3390\/cells13201730"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"57","DOI":"10.2220\/biomedres.45.57","article-title":"Indoxyl sulfate contributes to colorectal cancer cell proliferation and increased EGFR expression by activating AhR and Akt","volume":"45","author":"Ichisaka","year":"2024","journal-title":"Biomed. Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Ichisaka, Y., Takei, C., Naito, K., Higa, M., Yano, S., Niwa, T., and Shimizu, H. (2025). The Role of Indoxyl Sulfate in Exacerbating Colorectal Cancer During Chronic Kidney Disease Progression: Insights into the Akt\/\u03b2-Catenin\/c-Myc and AhR\/c-Myc Pathways in HCT-116 Colorectal Cancer Cells. Toxins, 17.","DOI":"10.3390\/toxins17010017"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Shimizu, H., and Niwa, T. (2026). Indoxyl Sulfate in the Gut-Kidney Axis: Pathophysiology and Clinical Significance in CKD-Associated Colorectal Cancer. Toxins, 18.","DOI":"10.3390\/toxins18020072"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1093\/ajcn\/32.1.173","article-title":"Microbial metabolites of tryptophan in the intestinal tract with special reference to skatole","volume":"32","author":"Yokoyama","year":"1979","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0301-6226(01)00189-0","article-title":"Review of microbiological and biochemical effects of skatole on animal production","volume":"71","author":"Deslandes","year":"2001","journal-title":"Livest. Prod. Sci."},{"key":"ref_38","first-page":"1","article-title":"Skatole: A thin red line between its benefits and toxicity","volume":"208","author":"Vrzal","year":"2023","journal-title":"Biochimie"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Rasmussen, M.K., Balaguer, P., Ekstrand, B., Daujat-Chavanieu, M., and Gerbal-Chaloin, S. (2016). Skatole (3-Methylindole) Is a Partial Aryl Hydrocarbon Receptor Agonist and Induces CYP1A1\/2 and CYP1B1 Expression in Primary Human Hepatocytes. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0154629"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1128\/AEM.02458-07","article-title":"Catabolic pathway for the production of skatole and indoleacetic acid by the acetogen Clostridium drakei, Clostridium scatologenes, and swine manure","volume":"74","author":"Whitehead","year":"2008","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1128\/aem.34.6.837-842.1977","article-title":"Isolation and characteristics of a skatole-producing Lactobacillus sp. from the bovine rumen","volume":"34","author":"Yokoyama","year":"1977","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4224","DOI":"10.1038\/s41467-018-06627-x","article-title":"Indoleacetate decarboxylase is a glycyl radical enzyme catalysing the formation of malodorant skatole","volume":"9","author":"Liu","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"11110","DOI":"10.1021\/jacs.1c13580","article-title":"Mechanistic Studies of a Skatole-Forming Glycyl Radical Enzyme Suggest Reaction Initiation via Hydrogen Atom Transfer","volume":"144","author":"Fu","year":"2022","journal-title":"J. Am. Chem. Soc."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/0378-4347(94)00065-4","article-title":"Gas chromatographic determination of indole and 3-methylindole (skatole) in bacterial culture media, intestinal contents and faeces","volume":"655","author":"Jensen","year":"1994","journal-title":"J. Chromatogr. B Biomed. Appl."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3180","DOI":"10.1128\/aem.61.8.3180-3184.1995","article-title":"3-Methylindole (skatole) and indole production by mixed populations of pig fecal bacteria","volume":"61","author":"Jensen","year":"1995","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/BF00391888","article-title":"Fecal skatole and indole and breath methane and hydrogen in patients with large bowel polyps or cancer","volume":"109","author":"Karlin","year":"1985","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1038\/s41564-024-01737-3","article-title":"Dietary fibre directs microbial tryptophan metabolism via metabolic interactions in the gut microbiota","volume":"9","author":"Sinha","year":"2024","journal-title":"Nat. Microbiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/s41522-026-00935-7","article-title":"pH regulates gut bacterial tryptophan metabolism","volume":"12","author":"Brinck","year":"2026","journal-title":"npj Biofilms Microbiomes"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"6956","DOI":"10.1021\/acs.jafc.2c08953","article-title":"Impact of High-Fiber or High-Protein Diet on the Capacity of Human Gut Microbiota To Produce Tryptophan Catabolites","volume":"71","author":"Huang","year":"2023","journal-title":"J. Agric. Food Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6333","DOI":"10.1021\/acs.jafc.0c00245","article-title":"High-Meat-Protein High-Fat Diet Induced Dysbiosis of Gut Microbiota and Tryptophan Metabolism in Wistar Rats","volume":"68","author":"Shi","year":"2020","journal-title":"J. Agric. Food Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/nrgastro.2016.165","article-title":"Diet, microorganisms and their metabolites, and colon cancer","volume":"13","year":"2016","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.phrs.2012.10.020","article-title":"The influence of diet on the gut microbiota","volume":"69","author":"Scott","year":"2013","journal-title":"Pharmacol. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1016\/j.cell.2016.05.041","article-title":"From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites","volume":"165","author":"Koh","year":"2016","journal-title":"Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"289","DOI":"10.4161\/gmic.19897","article-title":"Microbial degradation of complex carbohydrates in the gut","volume":"3","author":"Flint","year":"2012","journal-title":"Gut Microbes"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1152\/physrev.2001.81.3.1031","article-title":"Short-chain fatty acids and human colonic function: Roles of resistant starch and nonstarch polysaccharides","volume":"81","author":"Topping","year":"2001","journal-title":"Physiol. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1111\/j.1365-2036.2007.03562.x","article-title":"Review article: The role of butyrate on colonic function","volume":"27","author":"Hamer","year":"2008","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_57","first-page":"240","article-title":"Effect of dietary resistant starch and protein on colonic fermentation and intestinal tumourigenesis in rats","volume":"28","author":"Brown","year":"2007","journal-title":"Carcinogenesis"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"S192","DOI":"10.3177\/jnsv.65.S192","article-title":"Effects of Raw Potato Starch with High Resistant Starch Levels on Cecal Fermentation Properties in Rats","volume":"65","author":"Nagata","year":"2019","journal-title":"J. Nutr. Sci. Vitaminol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"239","DOI":"10.2527\/2003.811239x","article-title":"Effects of butyrate on apoptosis in the pig colon and its consequences for skatole formation and tissue accumulation","volume":"81","author":"Claus","year":"2003","journal-title":"J. Anim. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1017\/S1751731108002826","article-title":"Performances, meat quality and boar taint of castrates and entire male pigs fed a standard and a raw potato starch-enriched diet","volume":"2","author":"Pauly","year":"2008","journal-title":"Animal"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1017\/S0003356100020870","article-title":"The effects of dietary fibre, lactose and antibiotic on the levels of skatole and indole in faeces and subcutaneous fat in growing pigs","volume":"54","author":"Hawe","year":"1992","journal-title":"Anim. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1017\/S1357729800052590","article-title":"Effect of non-starch polysaccharides on production and absorption of indolic compounds in entire male pigs","volume":"74","author":"Knarreborg","year":"2002","journal-title":"Anim. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"311","DOI":"10.3934\/microbiol.2024016","article-title":"Why does increased microbial fermentation in the human colon shift toward butyrate?","volume":"10","author":"Flint","year":"2024","journal-title":"AIMS Microbiol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Yamamura, R., Inoue, K.Y., Nishino, K., and Yamasaki, S. (2023). Intestinal and fecal pH in human health. Front. Microbiomes, 2.","DOI":"10.3389\/frmbi.2023.1192316"},{"key":"ref_65","first-page":"183","article-title":"Intraluminal pH of the human gastrointestinal tract","volume":"46","author":"Fallingborg","year":"1999","journal-title":"Dan. Med. Bull."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"G922","DOI":"10.1152\/ajpgi.2001.280.5.G922","article-title":"The adherent gastrointestinal mucus gel layer: Thickness and physical state in vivo","volume":"280","author":"Atuma","year":"2001","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"15064","DOI":"10.1073\/pnas.0803124105","article-title":"The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria","volume":"105","author":"Johansson","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/s44185-024-00063-5","article-title":"pH Adaptation stabilizes bacterial communities","volume":"3","author":"Mougi","year":"2024","journal-title":"npj Biodivers."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1016\/j.chembiol.2023.07.015","article-title":"Mechanism-based inhibition of gut microbial tryptophanases reduces serum indoxyl sulfate","volume":"30","author":"Graboski","year":"2023","journal-title":"Cell Chem. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.chom.2016.10.021","article-title":"Modulation of a Circulating Uremic Solute via Rational Genetic Manipulation of the Gut Microbiota","volume":"20","author":"Devlin","year":"2016","journal-title":"Cell Host Microbe"}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/18\/9\/362\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T08:06:35Z","timestamp":1787645195000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/18\/9\/362"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,24]]},"references-count":70,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["toxins18090362"],"URL":"https:\/\/doi.org\/10.3390\/toxins18090362","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,24]]}}}