Abstract
BackgroundMicrobiota and bile acids in the gastrointestinal tract profoundly alter systemic metabolic processes. In obese subjects, gradual weight loss ameliorates adipose tissue inflammation and related systemic changes. We assessed how rapid weight loss due to a very low calorie diet (VLCD) affects the fecal microbiome and fecal bile acid composition, and their interactions with the plasma metabolome and subcutaneous adipose tissue inflammation in obesity.MethodsWe performed a prospective cohort study of VLCD-induced weight loss of 10% in ten grades 2–3 obese postmenopausal women in a metabolic unit. Baseline and post weight loss evaluation included fasting plasma analyzed by mass spectrometry, adipose tissue transcription by RNA sequencing, stool 16S rRNA sequencing for fecal microbiota, fecal bile acids by mass spectrometry, and urinary metabolic phenotyping by 1H-NMR spectroscopy. Outcome measures included mixed model correlations between changes in fecal microbiota and bile acid composition with changes in plasma metabolite and adipose tissue gene expression pathways.ResultsAlterations in the urinary metabolic phenotype following VLCD-induced weight loss were consistent with starvation ketosis, protein sparing, and disruptions to the functional status of the gut microbiota. We show that the core microbiome was preserved during VLCD-induced weight loss, but with changes in several groups of bacterial taxa with functional implications. UniFrac analysis showed overall parallel shifts in community structure, corresponding to reduced abundance of the genus Roseburia and increased Christensenellaceae;g__ (unknown genus). Imputed microbial functions showed changes in fat and carbohydrate metabolism. A significant fall in fecal total bile acid concentration and reduced deconjugation and 7-α-dihydroxylation were accompanied by significant changes in several bacterial taxa. Individual bile acids in feces correlated with amino acid, purine, and lipid metabolic pathways in plasma. Furthermore, several fecal bile acids and bacterial species correlated with altered gene expression pathways in adipose tissue.ConclusionsVLCD dietary intervention in obese women changed the composition of several fecal microbial populations while preserving the core fecal microbiome. Changes in individual microbial taxa and their functions correlated with variations in the plasma metabolome, fecal bile acid composition, and adipose tissue transcriptome.Trial Registration ClinicalTrials.gov NCT01699906, 4-Oct-2012, Retrospectively registered. URL-https://clinicaltrials.gov/ct2/show/NCT01699906
Highlights
Microbiota and bile acids in the gastrointestinal tract profoundly alter systemic metabolic processes
Weight loss was accompanied by improved insulin sensitivity, a pronounced fall in serum leptin, and decreased WBC and high-sensitivity C-reactive protein (hsCRP), but circulating uric acid levels did not change significantly (PreWL 6.2 ± 0.2, post weight loss (PostWL) 5.9 ± 0.4 p = 0.29)
The expression of gene pathways involved in fatty acid and phospholipid metabolism increased with parallel decreases in fatty acid synthesis gene expression
Summary
Microbiota and bile acids in the gastrointestinal tract profoundly alter systemic metabolic processes. We recently completed a study providing a VLCD fed to ten class 2–3 obese post-menopausal women (BMI > 35 kg/m2) in the metabolic facilities of the Rockefeller University Hospital to achieve rapid weight loss of 10% of baseline weight in a mean of 46 days [9]. This intervention reduced circulating leukocytes, high-sensitivity C-reactive protein (hsCRP), as well as IL6 and improved insulin sensitivity. As part of that study, we collected fresh fecal samples for analyses of microbiota and bile acids at baseline and after the planned weight loss had been achieved
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