Abstract

It is known that obesity is traceable to gut dysbiosis. Changes in the microbial ecosystem in the gut have major implications for the content of microbial signaling molecules in the host organism. The representation of tryptophan (Trp) signaling molecules in the gut will have a significant impact on intestinal microbiota diversity. Using metagenomic analysis, we investigated the taxonomic representation of the intestinal microbiota in healthy individuals and obese patients, which allowed us to reconstruct its potential metabolic activity depending on the level of Trp metabolites using PICRUSt software. We found that the key microbial Trp catabolite (MICT) are indole-3-lactate. Using the data of metagenomic sequencing analysis and bioinformatic tools we have analyzed a potential metabolic activity of the microbial communities or so-called «enzymatic landscape». We have found a twofold increase in the correlation between the content of Trp metabolites in feces and the «enzymatic landscape» of microbiome. The maximum number of statistically significant correlations between Trp metabolites and the potential metabolic activity of the microbial communities were established for indole-3-lactate. We have shown statistically significant relationships for indole-3-lactate and the abundance of genes for the metabolism of monosaccharides, nucleotides, amino acids, polyamines, and sulfosaccharides. It has been established that in obese patients there is a threefold increase in indole-3-lactate-producing microbiota. The phenotype of the microbiotic population is represented by completely different genera and species of microorganisms in obese individuals. The content of indole-3-lactate in the feces of obese patients mainly depends on the taxonomic representation of Escherichia-Shigella.

Keywords: tryptophan metabolites; indole-3-lactate; microbiome; obesity; enzymatic landscape

References

1. Singer-Englar T, Barlow G and Mathur R. “Obesity, diabetes, and the gut microbiome: an updated review”. Expert Rev Gastroenterol Hepatol 13 (2019): 3-15.
2. Burcelin R. “Gut microbiota and immune dialogue during metabolic disease”. Biol Aujourdhui 211 (2017): 1-18. French.
3. Crovesy L, Masterson D and Rosado EL. “Profile of the gut microbiota of adults with obesity: a systematic review”. Eur J Clin Nutr 74 (2020): 1251-1262.
4. Roager HM and Licht TR. “Microbial tryptophan catabolites in health and disease”. Nat Commun 9 ( 2018): 3294.
5. Cani PD. “Human gut microbiome hopes, threats and promises”. Gut 67 (2018): 1716-1725.
6. Zhao Q and Elson CO. “Adaptive immune education by gut microbiota antigens”. Immunology 154 (2018): 28-37.
7. Adak A and Khan MR. “An insight into gut microbiota and its functionalities”. Cell Mol Life Sci 76 (2019): 473-493.
8. Zmora N, Suez J and Elinav E. “You are what you eat: diet, health and the gut microbiota”. Nat Rev Gastroenterol Hepatol 16 (2019): 35-56.
9. Agus A, Clément K and Sokol H. “Gut microbiota-derived metabolites as central regulators in metabolic disorders”. Gut 70 (2021): 1174-1182.
10. Díaz-Garrido N, Badia J and Baldomà L. “Microbiota-derived extracellular vesicles in interkingdom communication in the gut”. J Extracell Vesicles 10 (2021): e12161.
11. Roth W., et al. “Tryptophan Metabolism and Gut-Brain Homeostasis”. Int J Mol Sci 22 (2021): 2973.
12. Thursby, E and Juge, N. “Introduction to the human gut microbiota”. Biochem J 474 (2017): 1823-1836.
13. Azriel S., et al. “An Intestinal Gut Organ Culture System for Analyzing Host-Microbiota Interactions”. J Vis Exp 172 (2021): 10.3791/62779.
14. Dahl WJ, Rivero Mendoza D and Lambert JM. “Diet, nutrients and the microbiome”. Prog Mol Biol Transl Sci 171 (2020): 237-263.
15. Magne F., et al. “The Firmicutes/Bacteroidetes Ratio: A Relevant Marker of Gut Dysbiosis in Obese Patients?”. Nutrients 12 (2020): 1474.
16. Rojas IY., et al. “Kynurenine-Induced Aryl Hydrocarbon Receptor Signaling in Mice Causes Body Mass Gain, Liver Steatosis, and Hyperglycemia”. Obesity (Silver Spring) 29 (2021): 337-349.
17. Vyhlídalová B., et al. “Gut Microbial Catabolites of Tryptophan Are Ligands and Agonists of the Aryl Hydrocarbon Receptor: A Detailed Characterization”. Int J Mol Sci 21 (2020): 2614.
18. Scott SA, Fu J and Chang PV. “Microbial tryptophan metabolites regulate gut barrier function via the aryl hydrocarbon receptor”. Proc Natl Acad Sci USA 117 (2020): 19376-19387.
19. Qu Y., et al. “A new interspecies and interkingdom signaling molecule-Indole”. Sheng Wu Gong Cheng Xue Bao 35 (2019): 2177-2188. Chinese.
20. Ji Y., et al. “Indole-3-Acetic Acid Alleviates Nonalcoholic Fatty Liver Disease in Mice via Attenuation of Hepatic Lipogenesis, and Oxidative and Inflammatory Stress”. Nutrients 11 (2019): 2062.
21. Mondanelli G., et al. “Amino acid metabolism as drug target in autoimmune diseases”. Autoimmun Rev 18 (2019): 334-348.
22. Tabassum F., et al. “Indole alkaloids from the leaves of Ravenia spectabilis engl. with activity against pancreatic cancer cell line”. Phytochemistry 186 (2021): 112744.
23. Shestopalov AV., et al. ““Kynurenine switch” and obesity”. Bulletin of Siberian Medicine 20 (2021): 103-111.
24. Ehrlich AM., et al. “Indole-3-lactic acid associated with Bifidobacterium-dominated microbiota significantly decreases inflammation in intestinal epithelial cells”. BMC Microbiol 20 (2020): 357.
25. Silveira EA., et al. “The Role of Sarcopenic Obesity in Cancer and Cardiovascular Disease: A Synthesis of the Evidence on Pathophysiological Aspects and Clinical Implications”. Int J Mol Sci 22 (2021): 4339.
26. Garcez ML., et al. “Sodium Butyrate and Indole-3-propionic Acid Prevent the Increase of Cytokines and Kynurenine Levels in LPS-induced Human Primary Astrocytes”. Int J Tryptophan Res 13 (2020): 1178646920978404.
27. Zhao L., et al. “Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes”. Science 359 (2018): 1151-1156.
28. Chepurny OG., et al. “Synthetic small molecule GLP-1 secretagogues prepared by means of a three-component indole annulation strategy”. Sci Rep 6 (2016): 28934.
29. Acar I., et al. “The role of calcium sensing receptors in GLP-1 and PYY secretion after acute intraduodenal administration of L-Tryptophan in rats”. Nutr Neurosci 23 (2020): 481-489.
30. Mosca A, Leclerc M and Hugot JP. “Gut Microbiota Diversity and Human Diseases: Should We Reintroduce Key Predators in Our Ecosystem?”. Front Microbiol 7 (2016): 455.
31. Silveira EA., et al. “The Role of Sarcopenic Obesity in Cancer and Cardiovascular Disease: A Synthesis of the Evidence on Pathophysiological Aspects and Clinical Implications”. Int J Mol Sci 22 (2021): 4339.
32. Zhang C., et al. “Dietary Modulation of Gut Microbiota Contributes to Alleviation of Both Genetic and Simple Obesity in Children”. EBioMedicine 2 (2015): 968-84.
33. https://www.genome.jp/pathway/map00380+C00954
34. http://qiime.org/
35. https://picrust.github.io/picrust/
36. Ai D., et al. “Association network analysis identifies enzymatic components of gut microbiota that significantly differ between colorectal cancer patients and healthy controls”. PeerJ 29 (2019): e7315.
37. RichaBharti and Dominik G. “Grimm Current challenges and best-practice protocols for microbiome analysis”. Briefings in Bioinformatics 22 (2021): 178-193.
38. https://www.microbiomeanalyst.ca/
39. Zakrzewski M., et al. “Calypso: a user-friendly web-server for mining and visualizing microbiome-environment interactions”. Bioinformatics 33 (2017): 782-783.
40. Ramos-Molina B., et al. “Dietary and Gut Microbiota Polyamines in Obesity- and Age-Related Diseases”. Front Nutr 6 (2019): 24.
41. Levy M, Thaiss CA and Elinav E. “Metabolites: messengers between the microbiota and the immune system”. Genes Dev 30 (2016): 1589-97.
42. Matsumoto M., et al. “Longevity in mice is promoted by probiotic-induced suppression of colonic senescence dependent on upregulation of gut bacterial polyamine production”. PLoS One 6 (2011): e23652.
43. Bonhoure N., et al. “Loss of the RNA polymerase III repressor MAF1 confers obesity resistance”. Genes Dev 29 (2015): 934-47.
44. Ishii I., et al. “Polyamine metabolism is involved in adipogenesis of 3T3-L1 cells”. Amino Acids 42 (2012): 619-26.
45. Sadasivan SK., et al. “Exogenous administration of spermine improves glucose utilization and decreases bodyweight in mice”. Eur J Pharmacol 729 (2014): 94-9.
46. Pedersen SB, Hougaard DM and Richelsen B. “Polyamines in rat adipocytes: their localization and their effects on the insulin receptor binding”. Mol Cell Endocrinol 62 (1989): 161-6.
47. Sharma M., et al. “Molecular Basis of Sulfosugar Selectivity in Sulfoglycolysis”. ACS Cent Sci 7 (2021): 476-487.
48. Frommeyer B., et al. “Environmental and Intestinal Phylum Firmicutes Bacteria Metabolize the Plant Sugar Sulfoquinovose via a 6-Deoxy-6-sulfofructose Transaldolase Pathway”. iScience 23 (2020): 101510.
49. Haange SB., et al. “Multiplexed Quantitative Assessment of the Fate of Taurine and Sulfoquinovose in the Intestinal Microbiome”. Metabolites 10 (2020): 430.
50. Huang W., et al. “The impact of indole-3-lactic acid on immature intestinal innate immunity and development: a transcriptomic analysis”. Sci Rep 11 (2021): 8088.

Citation

Olga P Shatova., et al. “«Enzymatic Landscape» of the Gut Microbiome". Clareus Scientific Medical Sciences 1.1 (2024): 19-31.

Copyright

2024 Olga P Shatova., et al. Licensee Clareus Scientific Publications. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.