Gut microbiota is one of the key suppliers of tryptophan metabolites, which perform various functions in the host organism, including their role as signaling molecules. Fecal microbiota transplantation (FMT) is widely used as a method for determining the contribution of microorganisms to the content of various metabolites in the holoorganism. In this regard, the aim of our study was to investigate the effect of FMT on the level of tryptophan metabolites in feces and blood in gnotobiotic mice. It was found that both before and after FMT, indole-3-lactate, and quinolinic acid were the dominant tryptophan metabolites in the intestine. FMT increased the content of both indoles (indole-3-acetate, indole-3-acrylate, indole-3-butyrate, indole-3-lactate) and kynurenines (anthranilic and xanthurenic acids) in the intestine. In serum of mice after FMT, indole metabolites (indole-3-butyrate, indole-3-carboxaldehyde, indole-3-lactate, indole-3-propionate) predominantly increased; however, tryptamine and xanthurenic acid also demonstrated a clear increase. The use of FMT demonstrates that the intestinal microbiota is a source of not only indole derivatives of tryptophan, but also metabolites of the kynurenine pathway.
Shatova O.P., Shestopalov A.V., Zlatnik E.Yu., Novikova I.A., Goncharova A.S., Maksimov A.Yu. (2025) The effect of fecal microbiota transplantation on levels of tryptophan metabolites in intestine and serum of gnotobiotic mice. Biomeditsinskaya Khimiya, 71(3), 209-216.
Shatova O.P. et al. The effect of fecal microbiota transplantation on levels of tryptophan metabolites in intestine and serum of gnotobiotic mice // Biomeditsinskaya Khimiya. - 2025. - V. 71. -N 3. - P. 209-216.
Shatova O.P. et al., "The effect of fecal microbiota transplantation on levels of tryptophan metabolites in intestine and serum of gnotobiotic mice." Biomeditsinskaya Khimiya 71.3 (2025): 209-216.
Shatova, O. P., Shestopalov, A. V., Zlatnik, E. Yu., Novikova, I. A., Goncharova, A. S., Maksimov, A. Yu. (2025). The effect of fecal microbiota transplantation on levels of tryptophan metabolites in intestine and serum of gnotobiotic mice. Biomeditsinskaya Khimiya, 71(3), 209-216.
References
Dong F., Hao F., Murray I.A., Smith P.B., Koo I., Tindall A.M., Kris-Etherton P.M., Gowda K., Amin S.G., Patterson A.D., Perdew G.H. (2020) Intestinal microbiota-derived tryptophan metabolites are predictive of Ah receptor activity. Gut Microbes, 12(1), 1–24. CrossRef Scholar google search
Illiano P., Brambilla R., Parolini C. (2020) The mutual interplay of gut microbiota, diet and human disease. FEBS J., 287(5), 833–855. CrossRef Scholar google search
Shatova O.P., Shestopalov A.V. (2023) Tryptophan metabolism: a new look at the role of tryptophan derivatives in the human body. Biol. Bull. Rev., 13(2), 81–91. CrossRef Scholar google search
Banfi D., Moro E., Bosi A., Bistoletti M., Cerantola S., Crema F., Maggi F., Giron M., Giaroni C., Baj A. (2021) Impact of microbial metabolites on microbiota-gut-brain axis in inflammatory bowel disease. Int. J. Mol. Sci., 22(4), 1623. CrossRef Scholar google search
Shatova O.P., Yagodkina E.M., Kaydoshko S.S., Zabolotneva A.A., Shestopalov A.V. (2023) Role of tryptophan metabolites and short-chain fatty acids in pathogenesis of autoimmune diseases. J. Evol. Biochem. Phys., 59(4), 1360–1373. CrossRef Scholar google search
Shatova O.P., Zabolotneva A.A., Mikin I.E., Bril D.V., Shestopalov A.V., Roumiantsev S.A. (2022) The role of tryptophan metabolites in metabolism and pathogenesis of obesity. Russian Journal of Preventive Medicine, 25(10), 97–103. CrossRef Scholar google search
Bernard A., le May C., Dastugue A., Ayer A., Blanchard C., Martin J.-C., Pais de Barros J.-P., Delaby P., le Bourgot C., Ledoux S. (2021) The tryptophan/kynurenine pathway: a novel cross-talk between nutritional obesity, bariatric surgery and taste of fat. Nutrients, 13(4), 1366. CrossRef Scholar google search
Zhang B., Chen T., Cao M., Yuan C., Reiter R.J., Zhao Z., Zhao Y., Chen L., Fan W., Wang X., Zhou X., Li C. (2022) Gut microbiota dysbiosis induced by decreasing endogenous melatonin mediates the pathogenesis of Alzheimer's disease and obesity. Front. Immunol., 13, 900132. CrossRef Scholar google search
Basson C., Serem J.C., Hlophe Y.N., Bipath P. (2023) An in vitro investigation of l-kynurenine, quinolinic acid, and kynurenic acid on B16 F10 melanoma cell cytotoxicity and morphology. Cell Biochem. Funct., 41(7), 912–922. CrossRef Scholar google search
Kumavath R., Pavithran H., Paul S., Anju V.T., Busi S., Dyavaiah M. (2024) Effects of gut microbiome and obesity on the development, progression and prevention of cancer (review). Int. J. Oncol., 64(1), 4. CrossRef Scholar google search
Jamshed L., Debnath A., Jamshed S., Wish J.V., Raine J.C., Tomy G.T., Thomas P.J., Holloway A.C. (2022) An emerging cross-species marker for organismal health: tryptophankynurenine pathway. Int. J. Mol. Sci., 23(11), 6300. CrossRef Scholar google search
Li X., Zhang B., Hu Y., Zhao Y. (2021) New insights into gut-bacteria-derived indole and its derivatives in intestinal and liver diseases. Front. Pharmacol., 12, 769501. CrossRef Scholar google search
Cervenka I., Agudelo L.Z., Ruas J.L. (2017) Kynurenines: tryptophan's metabolites in exercise, inflammation, and mental health. Science, 357(6349), eaaf9794. CrossRef Scholar google search
Cao Z.G., Qin X.B., Liu F.F., Zhou L.L. (2015) Tryptophan-induced pathogenesis of breast cancer. Afr. Health Sci., 15(3), 982–985. CrossRef Scholar google search
Sudar-Milovanovic E., Gluvic Z., Obradovic M., Zaric B., Isenovic E.R. (2022) Tryptophan metabolism in atherosclerosis and diabetes. Curr. Med. Chem., 29(1), 99–113. CrossRef Scholar google search
Chajadine M., Laurans L., Radecke T., Mouttoulingam N., Al-Rifai R., Bacquer E., Delaroque C., Rytter H., Bredon M., Knosp C., Vilar J., Fontaine C., Suffee N., Vandestienne M., Esposito B., Dairou J., Launay J.M., Callebert J., Tedgui A., Ait-Oufella H., Sokol H., Chassaing B., Taleb S. (2024) Harnessing intestinal tryptophan catabolism to relieve atherosclerosis in mice. Nat. Commun., 15(1), 6390. CrossRef Scholar google search
Baumgartner R., Forteza M.J., Ketelhuth D.J. (2019) The interplay between cytokines and the Kynurenine pathway in inflammation and atherosclerosis. Cytokine, 122, 154148. CrossRef Scholar google search
Alexeev E.E., Lanis J.M., Kao D.J., Campbell E.L., Kelly C.J., Battista K.D., Gerich M.E., Jenkins B.R., Walk S.T., Kominsky D.J., Colgan S.P. (2018) Microbiota-derived indole metabolites promote human and murine intestinal homeostasis through regulation of interleukin-10 receptor. Am. J. Pathol., 188(5), 1183–1194. CrossRef Scholar google search
Agus A., Planchais J., Sokol H. (2018) Gut microbiota regulation of tryptophan metabolism in health and disease. Cell Host Microbe, 23(6), 716–724. CrossRef Scholar google search
Lamas B., Richard M.L., Leducq V., Pham H.P., Michel M.L., da Costa G., Bridonneau C., Jegou S., Hoffmann T.W., Natividad J.M., Brot L., Taleb S., Couturier-Maillard A., Nion-Larmurier I., Merabtene F., Seksik P., Bourrier A., Cosnes J., Ryffel B., Beaugerie L., Launay J.M., Langella P., Xavier R.J., Sokol H. (2016) CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. Nat. Med., 22(6), 598–605. CrossRef Scholar google search
Bokoliya S.C., Dorsett Y., Panier H., Zhou Y. (2021) Procedures for fecal microbiota transplantation in murine microbiome studies. Front. Cell. Infect. Microbiol., 11, 711055. CrossRef Scholar google search
Shestopalov A.V., Kit O.I., Zabolotneva A.A., Zlatnik E.Y., Maksimov A.Y., Novikova I.A., Sagakyants A.B., Timofeeva S.V., Goncharova A.S., Galina A.V., Appolonova S.A., Markin P.A., Makarov V.V., Yudin S.M., Keskinov A.A., Roumiantsev S.A., Meshkov O.I. (2023) Alkylresorcinols as a new type of gut microbiota regulators influencing immune therapy efficiency in lung cancer treatment. Advanced Gut Microbiome Research, 2023, 2333767. CrossRef Scholar google search
Sigall Boneh R., van der Kruk N., Wine E., Verburgt C.M., de Meij T.G.J., Löwenberg M., Gecse K.B., Wierdsma N., Derikx J.P.M., de Jonge W.J., d'Haens G., Ghiboub M., van Limbergen J.E. (2025) Tryptophan metabolites profile predict remission with dietary therapy in pediatric Crohn's disease. Therap. Adv. Gastroenterol., 18, 17562848251323004. CrossRef Scholar google search
Bioanalytical Method Validation. Guidance for Industry. May 2018. U.S. Department of Health and Human Services. Food and Drug Administration. Scholar google search
Shestopalov A.V., Shatova O.P., Zabolotneva A.A., Gaponov A.M., Moskaleva N.E., Appolonova S.A., Makarov V.V., Yudin S.M., Rumyantsev A.G., Roumiantsev S.A. (2021) Coupling features of intestinal and serum indole pools in obesity. Problems of Biological, Medical and Pharmaceutical Chemistry, 24(10), 3–12. CrossRef Scholar google search
Zhang X., Akhtar M., Chen Y., Ma Z., Liang Y., Shi D., Cheng R., Cui L., Hu Y., Nafady A.A., Ansari A.R., Abdel-Kafy E.M., Liu H. (2023) Chicken jejunal microbiota improves growth performance by mitigating intestinal inflammation. Microbiome, 10(1), 107. CrossRef Scholar google search
Haq S., Grondin J.A., Khan W.I. (2021) Tryptophan-derived serotonin-kynurenine balance in immune activation and intestinal inflammation. FASEB J., 35(10), e21888. CrossRef Scholar google search
Hendrikx T., Schnabl B. (2019) Indoles: metabolites produced by intestinal bacteria capable of controlling liver disease manifestation. J. Intern. Med., 286(1), 32–40. CrossRef Scholar google search
Fazio F., Lionetto L., Curto M., Iacovelli L., Copeland C.S., Neale S.A., Bruno V., Battaglia G., Salt T.E., Nicoletti F. (2017) Cinnabarinic acid and xanthurenic acid: two kynurenine metabolites that interact with metabotropic glutamate receptors. Neuropharmacology, 112(Pt B), 365–372. CrossRef Scholar google search
Metidji A., Omenetti S., Crotta S., Li Y., Nye E., Ross E., Li V., Maradana M.R., Schiering C., Stockinger B. (2018) The environmental sensor AHR protects from inflammatory damage by maintaining intestinal stem cell homeostasis and barrier integrity. Immunity, 49(2), 353–362. CrossRef Scholar google search
Arora U., Kedia S., Ahuja V. (2024) The practice of fecal microbiota transplantation in inflammatory bowel disease. Intest. Res., 22(1), 44–64. CrossRef Scholar google search