Impact of short-term overfeeding of saturated or unsaturated fat or sugars on the gut microbiota in relation to liver fat in obese and overweight adults

Abstract

Backgrounds & aims: Intestinal microbiota may be causally involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). We aimed to study the effect of short-term overfeeding on human gut microbiota in relation to baseline and overfeeding-induced liver steatosis. We also asked whether the baseline microbiota composition is associated to the overfeeding-induced increase in liver fat. Methods: In a randomized trial, 38 overweight and obese subjects were assigned to consume an excess of 1000 kcal/day of diets rich in either saturated fat, unsaturated fat, or simple sugars for 3 weeks. Fasting blood samples and 1 H-MR spectroscopy were used for extensive clinical phenotyping as previously reported (PMID: 29844096). Fecal samples were collected for the analysis of the gut microbiota using 16S rRNA amplicon sequencing, imputed metagenomics and qPCR. Microbiota results were correlated with dietary intakes and clinical measurements before and during overfeeding. Results: The overall community structure of the microbiota remained highly stable and personalized during overfeeding based on between-sample BrayeCurtis dissimilarity, but the relative abundances of individual taxa were altered in a diet-specific manner: overfeeding saturated fat increased Proteobacteria, while unsaturated fat increased butyrate producers. Sugar overfeeding increased Lactococcus and Escherichia coli. Imputed functions of the gut microbiota were not affected by overfeeding. Several taxa affected by overfeeding significantly correlated with the changes in host metabolic markers. The baseline levels of proteobacterial family Desulfovibrionaceae, and especially genus Bilophila, were significantly associated to overfeeding-induced liver fat increase independently of the diet arm. In general, limited overlap was observed between the overfeeding-induced microbiota changes and the liver fat-associated microbiota features at baseline. Conclusions: Our work indicates that the human gut microbiota is resilient to short-term overfeeding on community level, but specific taxa are altered on diet composition-dependent manner. Generalizable microbiota signatures directly associated with liver steatosis could not be identified. Instead, the carriage of Bilophila was identified as a potential novel risk factor for diet-induced liver steatosis in humans. Clinical trial registry number: NCT02133144 listed on NIH website: ClinicalTrials.gov.

RETRACTED ARTICLE: Role of the gut microbiome in chronic diseases: a narrative review

“…Other recent studies have highlighted the role of the type of dietary fat on gut microbiome composition. In a randomized trial, 38 overweight and obese subjects were assigned to consume an excess of 1000 kcal/day of diets rich in saturated fat, unsaturated fat, or simple sugars for 3 weeks [ 159 ]. The relative abundances of individual taxa were altered in a diet-specific manner, wherein the overfeeding of saturated fat increased Proteobacteria , while unsaturated fat increased butyrate producers.…”

The Synbiotic Combination of Akkermansia muciniphila and Quercetin Ameliorates Early Obesity and NAFLD through Gut Microbiota Reshaping and Bile Acid Metabolism Modulation

“…Interestingly, the colonization seemed to be more successful in previously HFD-fed rats suggesting that the microenvironment created due to dietary patterns determined the ability of A. muciniphila to proliferate within its microbiota environment. Furthermore, some genera abundance was significantly modified in all quercetin-supplemented experimental groups, highlighting the decrease of Blautia, a genus highly detected in NAFLD patients, not only in adults but in pediatric patients too [ 40 , 56 ], and Coprobacillus, whose relative abundance has been previously associated with HFD [ 57 ]. Moreover, the relative abundance of Cyanobacteria phylum, which was reduced in HFD-fed rats, was increased due to the synbiotic supplementation, whereas Actinobacteria phylum, whose rise has been pointed out as a common marker of obesity [ 58 ], decreased with this combination.…”

Comprehensive Analysis of Fecal Microbiome and Metabolomics in Hepatic Fibrosis Rats Reveal Hepatoprotective Effects of Yinchen Wuling Powder From the Host-Microbial Metabolic Axis

“…Bilophila is significantly associated with fatty liver disease caused by overfeeding. High-fat diet can increase its proportion in gut microbiota and increase the risk of inflammatory bowel disease and hepatobiliary disease ( Jian et al, 2021 ). Moreover, both Desulfovibrio and Bilophila can produce LPS and promote inflammation ( Wei et al, 2015 ; Song et al, 2017 ).…”