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Nutritional components associated with IBD have been identified, and it is known that excessive methionine intake exacerbates inflammation, and that tryptophan metabolism is involved in inflammation. Analysis of the gut microbiota has also progressed, where <jats:italic>Lactobacillus<\/jats:italic> regulate immune cells in the intestine and suppress inflammation. However, whether the methionine and tryptophan metabolic pathways affect the growth of intestinal <jats:italic>Lactobacillus<\/jats:italic> is unknown. Here we show how transient methionine, tryptophan, and niacin deficiency affects the host and gut microbiota in mouse models of colitis (induced by dextran sodium sulfate) fed a methionine\u2010deficient diet (1K), tryptophan and niacin\u2010deficient diet (2K), or methionine, tryptophan, and niacin\u2010deficient diet (3K). These diets induced body weight decrease and 16S rRNA analysis of mouse feces revealed the alterations in the gut microbiota, leading to a dramatic increase in the proportion of <jats:italic>Lactobacillus<\/jats:italic> in mice. Intestinal RNA sequencing data confirmed that the expression of several serine proteases and fat\u2010metabolizing enzymes were elevated in mice fed with methionine, tryptophan, and niacin (MTN) deficient diet. In addition, one\u2010carbon metabolism and peroxisome proliferator\u2010activated receptor (PPAR) pathway activation were also induced with MTN deficiency. Furthermore, changes in the expression of various immune\u2010related cytokines were observed. These results indicate that methionine, tryptophan, and niacin metabolisms are important for the composition of intestinal bacteria and host immunity. Taken together, MTN deficiencies may serve as a Great Reset of gut microbiota and host gene expression to return to good health.<\/jats:p>","DOI":"10.1111\/cas.16153","type":"journal-article","created":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T03:38:50Z","timestamp":1714361930000},"page":"2473-2485","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Fat and proteolysis due to methionine, tryptophan, and niacin deficiency leads to alterations in gut microbiota and immune modulation in inflammatory bowel disease"],"prefix":"10.1111","volume":"115","author":[{"given":"Tomoaki","family":"Hara","sequence":"first","affiliation":[{"name":"Department of Medical Data Science, Center of Medical Innovation and Translational Research Osaka University Graduate School of Medicine  Osaka 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