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Surgeons regard clinical nutrition as a \u201clife\u2010saving\u201d discipline, pivotal in preserving the lives of numerous critically ill patients and facilitating the success of many surgical procedures. Parenteral nutrition (PN) support serves as a crucial component of clinical nutritional therapy, while a range of complications associated with total parenteral nutrition (TPN) can significantly undermine the efficacy of patient treatment. Impaired intestinal homeostasis is strongly associated with the occurrence and progression of TPN\u2010related infections, yet the underlying mechanisms remain poorly understood. In this study, RNA sequencing and single\u2010cell RNA sequencing (scRNA\u2010Seq) revealed that reduced secretion of interleukin\u201022 (IL\u201022) by intestinal Group 3 innate lymphoid cells (ILC3s) is a significant factor contributing to the onset of TPN\u2010related infections. Additionally, through 16S ribosomal RNA (16S rRNA) gene sequencing of the gut microbiota from patients with chronic intestinal failure and metagenomic sequencing analysis of the gut microbiota from mice, we observed that TPN reduced the abundance of <jats:italic>Lactobacillus murinus<\/jats:italic> (<jats:italic>L. murinus<\/jats:italic>), while supplementation with <jats:italic>L. murinus<\/jats:italic> could promote IL\u201022 secretion by ILC3s. Mechanistically, <jats:italic>L. murinus<\/jats:italic> upregulates indole\u20103\u2010carboxylic acid, which activates the nuclear receptor Ror\u03b3t to stimulate IL\u201022 secretion by ILC3s. This pathway strengthens gut barrier integrity and reduces infection susceptibility. Our findings enhance our understanding of the mechanisms driving the onset of TPN\u2010related infections, highlighting the critical role of gut microbiota in maintaining immune homeostasis and improving clinical outcomes.<\/jats:p>","DOI":"10.1002\/imt2.70007","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T05:23:27Z","timestamp":1741757007000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Gut microbiota\u2010derived tryptophan metabolites improve total parenteral nutrition\u2010associated infections by regulating Group 3 innate lymphoid cells"],"prefix":"10.1002","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9136-8625","authenticated-orcid":false,"given":"Longchang","family":"Huang","sequence":"first","affiliation":[{"name":"Department of General Surgery Jinling Hospital, Medical School of Nanjing University Nanjing 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