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, 16 (1), 244

Fecal Microbiota and Bile Acid Interactions With Systemic and Adipose Tissue Metabolism in Diet-Induced Weight Loss of Obese Postmenopausal Women

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Fecal Microbiota and Bile Acid Interactions With Systemic and Adipose Tissue Metabolism in Diet-Induced Weight Loss of Obese Postmenopausal Women

José O Alemán et al. J Transl Med.

Abstract

Background: Microbiota 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.

Methods: We 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.

Results: Alterations 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.

Conclusions: VLCD 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.

Keywords: Correlation analysis; Diet-induced weight loss; Fecal bile acids; Fecal bile acids-plasma metabolome; Fecal microbiota; Fecal microbiota-adipose tissue transcriptome; Gut microbiota-fecal bile acids; Gut microbiota-plasma metabolome; Obesity; Plasma metabolome.

Figures

Fig. 1
Fig. 1
Outline of pairwise correlation analyses performed
Fig. 2
Fig. 2
VLCD-induced weight loss modulates the fecal microbiome. Fecal samples were collected pre- and post-weight loss, 16S rRNA gene abundance determined via the MiSeq platform, and analyzed using QIIME 2. Microbial composition detected before and after the VLCD for the 20 most abundant taxa. The color key indicates specific bacterial taxa. All taxonomic analyses were performed at genus level, but some of the sequences detected were classified to groups with ambiguous genus-level names. Hence, Clostridiaceae does not actually indicate all members of the family Clostridiaceae, but rather all sequences classified as Clostridiaceae;g__ (i.e., family Clostridiaceae but unknown genus)
Fig. 3
Fig. 3
Diet induced weight loss shows conservation of the core gut microbiome. a Principal coordinate analysis (PCoA) of microbiome variation in pre-(blue circles) and post-(red circles) weight loss samples based on unweighted UniFrac analysis. The red lines connect the pre- and post-weight loss samples for each subject. For each subject, the positions along PC1 and PC3 did not change pre- and post-weight loss, whereas PC2 increased. b Average UniFrac Distance within subjects (red) versus between subjects (blue). c Imputed characterization of VLCD-induced gut functional changes induced by weight loss, as determined by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis. Colors indicate imputed bacterial pathways that decrease (green) or increase (red) with weight loss
Fig. 4
Fig. 4
Coordinated effects of VLCD-induced weight loss on the plasma metabolome and the fecal microbiome. a VLCD-induced weight loss is associated with changes in both selected fecal bacterial taxa and levels of plasma β-hydroxybutyrate. b Spearman correlation heat map for bacterial taxa (rows) versus plasma metabolites (columns) changing with weight loss at p-value < 0.1. Red denotes positive correlation (p < 0.1), dark red denotes strongly positive correlation (p < 0.05), blue denotes negative correlation (p < 0.1) while dark blue denotes strongly negative correlation (p < 0.05). c Spearman correlation bubble plot of total fecal microbiota versus selected plasma metabolite pathways
Fig. 5
Fig. 5
Coordinated effects of VLCD on fecal bile acids and microbiota. a Changes in total bile acids in feces following VLCD-induced weight loss (mean ± SE, *p < 0.05). b Spearman correlation heat map for bacterial taxa (rows) versus fecal bile acids (columns) changing with weight loss, at p-value < 0.1. Red denotes positive correlation (p < 0.1), dark red denotes strongly positive correlation (p < 0.05), blue denotes negative correlation (p < 0.1) while dark blue denotes strongly negative correlation (p < 0.05)
Fig. 6
Fig. 6
Coordinated effects of VLCD-induced weight loss on fecal bile acids and the plasma metabolome. a Spearman correlation heat map for plasma metabolites (rows) versus stool bile acids (columns) changing with weight loss at p-value < 0.1. Red denotes positive correlation (p < 0.1), dark red denotes strongly positive correlation (p < 0.05), blue denotes negative correlation (p < 0.1) while dark blue denotes strongly negative correlation (p < 0.05). b Spearman correlation bubble plot of total fecal bile acids versus selected plasma metabolite pathways
Fig. 7
Fig. 7
Coordinated effects of VLCD-induced weight loss on the fecal compartment and the adipose tissue transcriptome. a Spearman correlation heat map for adipose tissue transcriptome pathways (rows) versus fecal bile acids (columns) changing with weight loss, at p-value < 0.1. Red denotes positive correlation (p < 0.1), dark red denotes strongly positive correlation (p < 0.05), blue denotes negative correlation (p < 0.1) while dark blue denotes strongly negative correlation (p < 0.05). b Spearman correlation heat map for fecal microbiota taxa (rows) versus adipose tissue transcriptome pathways (columns) changing with weight loss, at p-value < 0.1. Red denotes positive correlation (p < 0.1), dark red denotes strongly positive correlation (p < 0.05), blue denotes negative correlation (p < 0.1) while dark blue denotes strongly negative correlation (p < 0.05)
Fig. 8
Fig. 8
Potential mechanisms of fecal microbiota, fecal bile acid, plasma metabolome and adipose tissue transcriptome interactions in diet-induced weight loss (Adapted with permission from Aleman et al. Gastroenterology 2014)

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