ISSN Print 2500–1094
ISSN Online 2542–1204
Bulletin of RSMU
BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)
ORIGINAL RESEARCH
Tryptophan catabolites and predicted gut flora enzyme-encoding genes
About authors
1 Pirogov Russian National Research Medical University, Moscow, Russia
2 Peoples' Friendship University of Russia, Moscow, Russia
3 Center for Digital and Translational Biomedicine, Center for Molecular Health, Moscow, Russia
4 Kazan (Volga Region) Federal University, Kazan, Russia
5 Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
6 Centre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical Biological Agency, Moscow, Russia
7 National Medical Research Center of Endocrinology, Moscow, Russia
Correspondence should be addressed: Olga P. Shatova
Ostrovityanova, 1, Moscow, 117997, Russia; moc.liamg@po.avotahs
About paper
Funding: the study was performed as part of the Assignment № 0373100122119000041 for the project “Creation of a bank of blood serum and fecal samples from healthy donors and patients with obesity, metabolic syndrome, type 2 diabetes mellitus, impaired mucosal barrier of the gastrointestinal tract with the aim of identifying candidate species-specific mediators of the quorum sensing human microbiota systems modulating the endocrine and metabolic function of adipose tissue”.
Author contribution: Shatova OP — primary data acquisition, statistical processing, manuscript writing and preparation of figures; Gaponov AM — manuscript writing; Grigoryeva TV — microbiome assessment; Vasiliev IYu — microbiome assessment and statistical data processing; Stoletova LS — data analysis; Makarov VV, Yudin SM — writing parts of the manuscript; Roumiantsev SA — study concept, manuscript editing; Shestopalov AV — study concept, data analysis, manuscript writing and editing.
Compliance with ethical standards: the study was approved by the Ethics Committee of the Pirogov Russian National Research Medical University (protocol No. 186 of 26 June 2019). All patients submitted the informed consent to the use of biomaterial for scientific purposes.
Received: 2023-06-21
Accepted: 2023-07-20
Published online: 2023-08-07
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Fig. 1. MICT formation and role in human organism: indole-3-acetate and indole-3-propionate regulate hepatic lipogenesis and prevent fatty degeneration of the liver (1); indole-3-propionate has a neuroprotective effect; indole-3-lactate is responsible for axonal growth and cognitive ability (2); indole-3-propionate regulates permeability of the mucosal barrier, it increases the synthesis of tight junction proteins, reduces production of tumor necrosis factor-α (TNF-α) and possesses antioxidant activity (3); in the pancreas, MICT suppress autoimmune inflammation and prevent type 1 diabetes mellitus; furthermore, it has been shown that indole-3-acetate suppresses tumor cell proliferation in the pancreas (4); indole-3-acetate reduces production of pro-inflammatory cytokines by macrophages; indole-3-acetaldehyde increases production of interleukin 22 (IL-22) in immune cells, including intestinal cells (5); in adipose tissue, indole-3-acetate and indole-3-propionate have an anti-inflammatory effect, thereby preventing insulin resistance (6)
Fig. 2. Quantitative analysis of the correlations “tryptophan catabolite — predicted gut microbiome enzyme-encoding gene abundance”. In healthy individuals, anthranilic acid and indole-3-acrylate are the key catabolites that are closely linked to the predicted gut microbiome enzyme-encoding gene abundance. In obese individuals, indole, indole-3-lactate, kynurenic and quinolinic acids are correlated to the predicted gut microbiome enzyme-encoding gene abundance
Fig. 3. Obesity is associated with significant deviations of the link between the indole-3-lactate levels and the predicted gut microbiome enzyme-encoding gene abundance. In healthy donors, a total of five significant correlation pairs between indole-3-lactate and the predicted gut microbiome enzyme-encoding gene abundance were identified, while obese individuals showed a significant microbiome enrichment having significant correlation pairs for the fecal levels of indole-3-lactate and the predicted abundance of genes encoding the enzymes involved in various metabolic pathways. ⬇ — decrease in the concentration of MICT in fecal samples; 1 — indole-3-pyruvate affects cells of the intestine (via AhR) and determines the tight junction integrity; 2 — indole-3-acetate, indole-3-propionate, and indole-3-lactate affect immune cells of the intestine (via AhR), increase the pathogen resistance and decrease the intestinal barrier permeability; 3 — interspecies-specific molecule QS — indole having a constant concentration
Table 1. Fecal levels of tryptophan metabolites in adults, nmol/g
Note: * — the difference is significant at р < 0.05.
Table 2. Correlation “fecal levels of indole-3-lactate – predicted gut microbiome enzyme-encoding gene abundance” in obese patients
