Circulating bacterial signature is linked to metabolic disease and shifts with metabolic alleviation after bariatric surgery

Abstract

Background The microbiome has emerged as an environmental factor contributing to obesity and type 2 diabetes (T2D). Increasing evidence suggests links between circulating bacterial components (i.e., bacterial DNA), cardiometabolic disease, and blunted response to metabolic interventions. In this aspect, thorough next-generation sequencing-based and contaminant-aware approaches are lacking. To address this, we tested whether bacterial DNA could be amplified in the blood of subjects with obesity and high metabolic risk under strict experimental and analytical control and whether a putative bacterial signature is related to metabolic improvement after bariatric surgery. Methods Subjects undergoing bariatric surgery were recruited into sex- and BMI-matched subgroups with (n = 24) or without T2D (n = 24). Bacterial DNA in the blood was quantified and prokaryotic 16S rRNA gene amplicons were sequenced. A contaminant-aware approach was applied to derive a compositional microbial signature from bacterial sequences in all subjects at baseline and at 3 and 12 months after surgery. We modeled associations between bacterial load and composition with host metabolic and anthropometric markers. We further tested whether compositional shifts were related to weight loss response and T2D remission. Lastly, bacteria were visualized in blood samples using catalyzed reporter deposition (CARD)-fluorescence in situ hybridization (FISH). Results The contaminant-aware blood bacterial signature was associated with metabolic health. Based on bacterial phyla and genera detected in the blood samples, a metabolic syndrome classification index score was derived and shown to robustly classify subjects along their actual clinical group. T2D was characterized by decreased bacterial richness and loss of genera associated with improved metabolic health. Weight loss and metabolic improvement following bariatric surgery were associated with an early and stable increase of these genera in parallel with improvements in key cardiometabolic risk parameters. CARD-FISH allowed the detection of living bacteria in blood samples in obesity. Conclusions We show that the circulating bacterial signature reflects metabolic disease and its improvement after bariatric surgery. Our work provides contaminant-aware evidence for the presence of living bacteria in the blood and suggests a putative crosstalk between components of the blood and metabolism in metabolic health regulation.

The Role of Gut Microbiota and Its Produced Metabolites in Obesity, Dyslipidemia, Adipocyte Dysfunction, and Its Interventions

“…Chakaroun et al investigated 64 individuals with and without T2DM undergoing bariatric surgery and identified a bacterial blood signature in correlation with features of the metabolic syndrome, formulating a metabolic syndrome classification index based on bacterial phylum and genus level abundances. The study also found that the weight loss and improvement of metabolic syndrome after bariatric surgery was associated with bacterial composition, quantity, and their identified taxonomic signatures [ 203 ]. The three mentioned studies investigated only 25, 24, and 64 individuals, respectively [ 201 , 202 , 203 ]; thus, larger studies are needed to evaluate whether benefits of bariatric surgery on dyslipidemia are, at least in part, through changes in gut microbiota or its metabolite production.…”

“…The study also found that the weight loss and improvement of metabolic syndrome after bariatric surgery was associated with bacterial composition, quantity, and their identified taxonomic signatures [ 203 ]. The three mentioned studies investigated only 25, 24, and 64 individuals, respectively [ 201 , 202 , 203 ]; thus, larger studies are needed to evaluate whether benefits of bariatric surgery on dyslipidemia are, at least in part, through changes in gut microbiota or its metabolite production.…”

New Paradigms for Familiar Diseases: Lessons Learned on Circulatory Bacterial Signatures in Cardiometabolic Diseases

“…In our cohort, several of these genera were positively correlated with inflammation, fat mass, and body mass index (BMI). Most importantly, 40% of the variance in the blood bacterial composition could be explained by 27 host variables, including medication intake 22 . Similarly, bacterial composition predicted the clinical classification of patients according to metabolic disease robustly.…”

“…Therefore, it is surprising that the notion of a core blood bacterial signature in health and its divergence in disease with accompanying systemic response remains contentious. However, converging evidence for microbial signatures in metabolic tissues, including the blood, suggests a novel paradigm for metabolic disease development [19][20][21][22][23][24]. In this review, we address the potential clinical relevance of a blood bacterial signature pertinent to disease development and outcomes and new avenues for translational approaches.…”

Circulating Bacterial DNA: A New Paradigm for Cancer Diagnostics

“…To date, identification of microbes in the circulatory system has mainly been applied to infectious disease and sepsis, where sequencing of cfDNA has improved detection of micro-organisms that are difficult to culture, and has augmented traditional culture techniques ( 6 , 7 ). Emerging research in the field of cfDNA has identified highly divergent cbDNA in a variety of non-communicable diseases, including liver ( 8 ), metabolic ( 9 ), autoimmune ( 10 ), and cardiovascular disease ( 11 , 12 ). Although the source, route of access and significance of this cbDNA in disease states has yet to be fully elucidated ( 3 ), several studies have identified DNA from common gut commensal bacteria in patient plasma samples.…”