Dietary butyrate ameliorates metabolic health associated with selective proliferation of gut Lachnospiraceae bacterium 28-4
Zhuang Li, Enchen Zhou, Cong Liu, Hope Wicks, Sena Yildiz, Farhana Razack, Zhixiong Ying, Sander Kooijman, Debby P.Y. Koonen, Marieke Heijink, Sarantos Kostidis, Martin Giera, Ingrid M.J.G. Sanders, Ed J. Kuijper, Wiep Klaas Smits, Ko Willems van Dijk, Patrick C.N. Rensen, Yanan Wang
Zhuang Li, Enchen Zhou, Cong Liu, Hope Wicks, Sena Yildiz, Farhana Razack, Zhixiong Ying, Sander Kooijman, Debby P.Y. Koonen, Marieke Heijink, Sarantos Kostidis, Martin Giera, Ingrid M.J.G. Sanders, Ed J. Kuijper, Wiep Klaas Smits, Ko Willems van Dijk, Patrick C.N. Rensen, Yanan Wang
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Research Article Endocrinology Microbiology

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

Abstract

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.

Authors

Zhuang Li, Enchen Zhou, Cong Liu, Hope Wicks, Sena Yildiz, Farhana Razack, Zhixiong Ying, Sander Kooijman, Debby P.Y. Koonen, Marieke Heijink, Sarantos Kostidis, Martin Giera, Ingrid M.J.G. Sanders, Ed J. Kuijper, Wiep Klaas Smits, Ko Willems van Dijk, Patrick C.N. Rensen, Yanan Wang

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Figure 5

Butyrate treatment does not induce weight loss, ameliorate metabolic health, or promote Lachnospiraceae bacterium 28-4 in DIO mice.

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Butyrate treatment does not induce weight loss, ameliorate metabolic hea...
(A) Mice were rendered DIO by being fed an HFD for 10 weeks and subsequently fed an HFD without or with 5% (w/w) butyrate for another 6 weeks. (B) BW was measured weekly (n = 7–9) and (C) body composition was measured at the end of the treatment period by MRI (n = 7–9). (D) The average food intake per day was calculated (n = 7–9). (E) Fasting plasma glucose (n = 7–9) and (F) insulin (n = 6) were measured and (G) used to calculate HOMA-IR (n = 6). Cecum bacterial DNA was collected for 16S rRNA-Seq and (H) the observed richness of taxonomy (n = 7–9) and (I) Shannon diversity (n = 7–9) of gut microbiota were calculated. (J) The composition of abundant bacteria on phylum (n = 7–9) and (K) PCoA plot of unweighted UniFrac distances on OTU level (n = 7–9) were calculated. (L) The abundance of Lachnospiraceae bacterium 28-4 was quantified by real-time PCR (n = 8–9). Data are shown as means ± SEM for B–G and L or box plot with whiskers at min/max for H and I. Statistical significance between 2 groups was determined with 2-tailed Student’s unpaired t test. For data represented in the line graphs showing the changes over time for a continuous variable, statistical significance between 2 groups at each time point was determined using 2-tailed Student’s unpaired t test.