Dietary butyrate ameliorates metabolic health associated with selective proliferation of gut Lachnospiraceae bacterium 28-4

• Published in: JCI insight Vol. 8; no. 4
• Main Authors: Li, Zhuang, Zhou, Enchen, Liu, Cong, Wicks, Hope, Yildiz, Sena, Razack, Farhana, Ying, Zhixiong, Kooijman, Sander, Koonen, Debby PY, Heijink, Marieke, Kostidis, Sarantos, Giera, Martin, Sanders, Ingrid MJG, Kuijper, Ed J, Smits, Wiep Klaas, van Dijk, Ko Willems, Rensen, Patrick CN, Wang, Yanan
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 22.02.2023; American Society for Clinical investigation
• Subjects: Animals; Butyrates - adverse effects; Cell Proliferation; Endocrinology; Humans; Metabolic Syndrome; Mice; Microbiology; Obesity - metabolism; RNA, Ribosomal, 16S; Weight Gain; Microbiology; Obesity; Endocrinology
• ISSN: 2379-3708; 2379-3708
• DOI: 10.1172/jci.insight.166655

Short-chain fatty acids, including butyrate, have multiple metabolic benefits in individuals who are lean but not in individuals with metabolic syndrome, with the underlying mechanisms still being unclear. We aimed to investigate the role of gut microbiota in the induction of metabolic benefits of dietary butyrate. We performed antibiotic-induced microbiota depletion of the gut and fecal microbiota transplantation (FMT) in APOE*3-Leiden.CETP mice, a well-established translational model for developing human-like metabolic syndrome, and revealed that dietary butyrate reduced appetite and ameliorated high-fat diet-induced (HFD-induced) weight gain dependent on the presence of gut microbiota. FMT from butyrate-treated lean donor mice, but not butyrate-treated obese donor mice, into gut microbiota-depleted recipient mice reduced food intake, attenuated HFD-induced weight gain, and improved insulin resistance. 16S rRNA and metagenomic sequencing on cecal bacterial DNA of recipient mice implied that these effects were accompanied by the selective proliferation of Lachnospiraceae bacterium 28-4 in the gut as induced by butyrate. Collectively, our findings reveal a crucial role of gut microbiota in the beneficial metabolic effects of dietary butyrate as strongly associated with the abundance of Lachnospiraceae bacterium 28-4.