Obese Individuals with and without Type 2 Diabetes Show Different Gut Microbial Functional Capacity and Composition

Thingholm, Louise B.; Rühlemann, Malte; Koch, Manja; Fuqua, Brie K.; Laucke, Guido; Boehm, Ruwen; Bang, Corinna; Franzosa, Eric A.; Hübenthal, Matthias; Rahnavard, Ali; Frost, Fabian; Lloyd-Price, Jason; Schirmer, Melanie; Lusis, Aldons J.; Vulpe, Chris D.; Lerch, Markus M.; Homuth, Georg; Kacprowski, Tim; Schmidt, Carsten Oliver; Nöthlings, Ute; Karlsen, Tom H.; Lieb, Wolfgang; Laudes, Matthias; Franke, André; Huttenhower, Curtis

doi:10.1016/j.chom.2019.07.004

Cited by 294 publications

(205 citation statements)

References 81 publications

(121 reference statements)

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“…In fact, diabetes state-driven bacterial deposition in plasma was found to be significantly lower than that of negative controls when data were corrected by 16S rRNA gene load, which further supports the biological relevance of our findings. Furthermore, Escherichia-Shigella was shown to be enriched in the plasma of patients with diabetes, which is in agreement with several previous studies that reported higher levels of Escherichia-Shigella in the faeces of individuals with dysglycaemia 8,23,24 .…”

Section: Discussionsupporting

confidence: 92%

“…4j). Our findings corroborate previous reports that link the family Enterobacteriaceae to poor glycaemic control 23,24 and Faecalibacterium 22,24,25 , Odoribacter 26 and Alistipes 22,24,27 to leanness and positive metabolic outcomes, which suggests that these taxa can find a niche in the MAT to modulate glucose homeostasis in the host. Bilophila is a genus that contains bile acid-resistant bacteria that are generally linked to obesity 28 ; however, its effect on blood glucose regulation without the confounding factor of obesity is largely unknown.…”

Section: Metabolic Tissues Display Specific Bacterial Dna Signaturessupporting

confidence: 92%

“…These findings are in line with higher levels of Enterobacteriaceae being a strong predictor of higher glycaemic load after a meal 23 . Furthermore, Escherichia-Shigella has been linked to insulin resistance 8 and has been shown to be the sole taxon that is enriched in patients with T2D when accounting for the confounding factors of obesity and glucose-lowering treatments 24 . Our findings add to this previous knowledge as they show that live and/or fragmented Escherichia-Shigella, as well as other Enterobacteriaceae, can access and build up in the circulatory compartment potentially affecting glucose homeostasis.…”

Section: Metabolic Tissues Display Specific Bacterial Dna Signaturesmentioning

confidence: 99%

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Type 2 diabetes influences bacterial tissue compartmentalisation in human obesity

et al. 2020

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Visceral obesity is a key risk factor for type 2 diabetes (T2D). Whereas gut dysbiosis appears to be instrumental for this relationship, whether gut-associated signatures translocate to extra-intestinal tissues and how this affects host metabolism remain elusive. Here we provide a comparative analysis of the microbial profile found in plasma, liver and in three distinct adipose tissues of individuals with morbid obesity. We explored how these tissue microbial signatures vary between individuals with normoglycaemia and those with T2D that were matched for body mass index. We identified tissue-specific signatures with higher bacterial load in the liver and omental adipose tissue. Gut commensals, but also environmental bacteria, showed tissueand T2D-specific compartmentalisation. T2D signatures were most evident in mesenteric adipose tissue, in which individuals with diabetes displayed reduced bacterial diversity concomitant with fewer Gram-positive bacteria, such as Faecalibacterium, as opposed to enhanced levels of typically opportunistic Gram-negative Enterobacteriaceae. Plasma samples of individuals with diabetes were similarly enriched in Enterobacteriaceae, including the pathobiont Escherichia-Shigella. Our work provides evidence for the presence of selective plasma and tissue microbial signatures in individuals with severe obesity and identifies new potential microbial targets and biomarkers of T2D.

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Section: Discussionsupporting

confidence: 92%

Section: Metabolic Tissues Display Specific Bacterial Dna Signaturessupporting

confidence: 92%

Section: Metabolic Tissues Display Specific Bacterial Dna Signaturesmentioning

confidence: 99%

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Type 2 diabetes influences bacterial tissue compartmentalisation in human obesity

et al. 2020

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“…Therefore, although not considered a probiotic, A. muciniphila is showing promising preliminary data in humans (Depommier et al, 2019). Similar to A. muciniphila, F. prausnitzii is another commensal depleted in obese subjects and type 2 diabetic patients and also during inflammatory bowel diseases (Sokol et al, 2008;Thingholm et al, 2019) that displays specific anti-inflammatory properties on the gut (Sokol et al, 2008). Among the different mechanisms involved in reinforcement of the gut barrier, the bacteria and yeast detailed above act via different pathways, including the production of short-chain fatty acids (e.g., butyrate and propionate) that contribute to the regulation of numerous functions ranging from the regulation of gene expression via histone deacetylases to binding to specific G protein-coupled receptors, such as GPR-43 and GPR-41 (Le Poul et al, 2003;Kimura et al, 2014).…”

Section: Probiotics and The Gut Barrier Functionmentioning

confidence: 99%

How Probiotics Affect the Microbiota

Wieërs

Belkhir

Enaud

et al. 2020

Front. Cell. Infect. Microbiol.

292

166

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Probiotics have been used to treat a variety of diseases for decades; however, what is the rationale for their application? Such a treatment was first proposed in the early nineteenth century based on observations of decreased bifidobacterial populations in children suffering from diarrhea, suggesting that oral intake of bifidobacteria could replete this subpopulation of the microbiota and improve health. Since then, studies have shown modifications in the gut or skin microbiota in the course of a variety of diseases and suggested positive effects of certain probiotics. Most studies failed to report any impact on the microbiota. The impact of probiotics as well as of bacteria colonizing food does not reside in their ability to graft in the microbiota but rather in sharing genes and metabolites, supporting challenged microbiota, and directly influencing epithelial and immune cells. Such observations argue that probiotics could be associated with conventional drugs for insulin resistance, infectious diseases, inflammatory diseases, and psychiatric disorders and could also interfere with drug metabolism. Nevertheless, in the context of a plethora of probiotic strains and associations produced in conditions that do not allow direct comparisons, it remains difficult to know whether a patient would benefit from taking a particular probiotic. In other words, although several mechanisms are observed when studying a single probiotic strain, not all individual strains are expected to share the same effects. To clarify the role of probiotics in the clinic, we explored the relation between probiotics and the gut and skin microbiota.

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“…Oscillibacter was associated with cohort-wide obesity irrespective of site. The association of Oscillibacter to obesity has been previously reported in a European cohort 67 . Overall, the lean comparisons showed slightly greater diversity than the obese groups with taxa representative of eight different phyla ( Figure 5A).…”

Section: Algerian Tuaregs Saudi Bedouins and Amazonians From Frenchmentioning

confidence: 51%

Gut Microbiome Profiling of a Rural and Urban South African Cohort Reveals Biomarkers of a Population in Lifestyle Transition

Oduaran

Tamburini

Sahibdeen

et al. 2020

Preprint

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Background: Comparisons of traditional hunter-gatherers and pre-agricultural communities in Africa with urban and suburban Western North American and European cohorts have clearly shown that diet, lifestyle and environment are associated with gut microbiome composition. Yet, little is known about the gut microbiome composition of most African adults. South Africa comprises a richly diverse ethnolinguistic population that is experiencing an ongoing epidemiological transition and concurrent spike in the prevalence of obesity, largely attributed to a shift towards more Westernized diets and increasingly inactive lifestyle practices. To better characterize the microbiome of African adults living in more mainstream lifestyle settings and to investigate associations between the microbiome and obesity, we conducted a pilot study in two South African cohorts that are representative of urban and rural populations. The study was designed collaboratively with community leaders. As the rate of overweight and obesity is particularly high in women, we collected single time-point stool samples from 170 HIV-negative women (51 at Soweto; 119 at Bushbuckridge), performed 16S rRNA gene sequencing on these samples and compared the data to concurrently collected anthropometric data. Results:We found the overall gut microbiome of our cohorts to be reflective of their ongoing epidemiological transition. Specifically, our results show a relatively higher than expected abundance of Western gut-associated taxa such as Barnesiella and the presence of Bifidobacteria and Bacteroides together with the more traditionally non-Western gut-associated Prevotella, Treponema and Succinivibrio. Interestingly, we observed a relatively higher abundance of the Melainabacteria, Vampirovibrio, a predatory bacterium, in the rural cohort. We also found Prevotella, despite its generally high prevalence relative to all taxa present in the cohort, to be associated with obesity. Conclusions:Altogether, this work identifies putative microbial features associated with host health in a historically understudied community. Furthermore, we note the crucial role of community engagement to the success of a study in an African setting, the importance of more population-specific studies to inform targeted interventions as well as present a basic foundation for future research in this regard.

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Obese Individuals with and without Type 2 Diabetes Show Different Gut Microbial Functional Capacity and Composition

Cited by 294 publications

References 81 publications

Type 2 diabetes influences bacterial tissue compartmentalisation in human obesity

Type 2 diabetes influences bacterial tissue compartmentalisation in human obesity

How Probiotics Affect the Microbiota

Gut Microbiome Profiling of a Rural and Urban South African Cohort Reveals Biomarkers of a Population in Lifestyle Transition

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