{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T06:53:21Z","timestamp":1776840801083,"version":"3.51.2"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Liver failure is a severe condition marked by circulatory failure, systemic inflammation, and gut microbial dysbiosis. This dysbiosis worsens liver damage by reducing beneficial metabolites and increasing harmful products. This study investigates the effects of probiotics on gut microbial functional pathways in liver failure. The aim is to link microbial metabolic reprogramming with host biochemical, inflammatory, and gut barrier responses through functional metagenomic reconstruction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Acute liver failure was induced in male Wistar rats using D-galactosamine (700 mg\/kg) and lipopolysaccharide (10 \u03bcg\/kg). Probiotic treatment began 24 hours after induction and was administered daily for 14 consecutive days before euthanasia. Two doses were used: low (1\u00d710\u2078 CFU\/day) and high (1\u00d710\u2079 CFU\/day). Fecal samples underwent shotgun metagenomic sequencing, followed by functional pathway reconstruction. These predictions were validated using metabolite profiling, quantitative PCR of microbial genes, intestinal barrier assays, and immune cell cytokine analysis. Host phenotypic markers were correlated with microbial pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and discussion<\/jats:title>\n                    <jats:p>Liver failure significantly elevated serum ALT (42.6\u00b16.8 to 512.4\u00b148.9 U\/L), AST (78.3\u00b19.5 to 684.7\u00b162.1 U\/L), and plasma ammonia (38.9\u00b15.2 to 128.6\u00b114.3 \u03bcmol\/L). Probiotic supplementation showed a dose-dependent improvement. ALT dropped to 382.7\u00b141.6 U\/L (low dose) and 248.9\u00b132.4 U\/L (high dose). Ammonia levels decreased to 86.4\u00b19.7 \u03bcmol\/L and 59.8\u00b17.6 \u03bcmol\/L, respectively. Metagenomic analysis revealed a 1.7- and 2.6-fold increase in short-chain fatty acid (SCFA) biosynthesis pathways and a 38% and 61% decrease in urease-associated nitrogen metabolism. These changes were confirmed by higher fecal SCFAs (31.8\u00b14.2 to 63.9\u00b16.4 mM), lower ammonia (8.9\u00b11.1 to 3.7\u00b10.5 mM), improved intestinal barrier integrity (TEER: 462\u00b138 to 721\u00b144 \u03a9\u00b7cm\u00b2), and reduced TNF-\u03b1 (214.6\u00b122.8 to 74.9\u00b112.3 pg\/mL). Probiotic supplementation significantly reprogrammed the gut microbiome in liver failure. This highlights its potential as a therapeutic modulator of the gut\u2013liver axis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1799729","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T05:54:40Z","timestamp":1776837280000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Functional metagenomic reconstruction of microbial pathways altered by probiotic supplementation in liver failure"],"prefix":"10.3389","volume":"16","author":[{"given":"Junli","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Nanfang Hospital, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhan","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Nanfang Hospital, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinzi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Nanfang Hospital, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nuo","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Nanfang Hospital, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guoqin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Nanfang Hospital, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiawei","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Nanfang Hospital, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cai","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Nanfang Hospital, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41540-021-00210-9","article-title":"Metabolic modeling of host\u2013microbe interactions for therapeutics in colorectal cancer","volume":"8","author":"Bhalla","year":"2022","journal-title":"NPJ Syst. 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