The link between the microbes in the human gut and the development of obesity, cardiovascular disease and metabolic syndromes, such as type 2 diabetes, is becoming clearer. However, because of the ...complexity of the microbial community, the functional connections are less well understood. Studies in both mice and humans are helping to show what effect the gut microbiota has on host metabolism by improving energy yield from food and modulating dietary or the host-derived compounds that alter host metabolic pathways. Through increased knowledge of the mechanisms involved in the interactions between the microbiota and its host, we will be in a better position to develop treatments for metabolic disease.
Metagenomics studies have shown that type 2 diabetes (T2D) is associated with an altered gut microbiota. Whereas different microbiota patterns have been observed in independent human cohorts, ...reduction of butyrate-producing bacteria has consistently been found in individuals with T2D, as well as in those with prediabetes. Butyrate is produced in the large intestine by microbial fermentations, particularly of dietary fiber, and serves as primary fuel for colonocytes. It also acts as histone deacetylase inhibitor and ligand to G-protein coupled receptors, affecting cellular signaling in target cells, such as enteroendocrine cells. Therefore, butyrate has become an attractive drug target for T2D, and treatment strategies have been devised to increase its intestinal levels, for example by supplementation of butyrate-producing bacteria and dietary fiber, or through fecal microbiota transplant (FMT). In this review, we provide an overview of current literature indicating that these strategies have yielded encouraging results and short-term benefits in humans, but long-term improvements of glycemic control have not been reported so far. Further studies are required to find effective approaches to restore butyrate-producing bacteria and butyrate levels in the human gut, and to investigate their impact on glucose regulation in T2D.
Dietary lipids may influence the abundance of circulating inflammatory microbial factors. Hence, inflammation in white adipose tissue (WAT) induced by dietary lipids may be partly dependent on their ...interaction with the gut microbiota. Here, we show that mice fed lard for 11 weeks have increased Toll-like receptor (TLR) activation and WAT inflammation and reduced insulin sensitivity compared with mice fed fish oil and that phenotypic differences between the dietary groups can be partly attributed to differences in microbiota composition. Trif−/− and Myd88−/− mice are protected against lard-induced WAT inflammation and impaired insulin sensitivity. Experiments in germ-free mice show that an interaction between gut microbiota and saturated lipids promotes WAT inflammation independent of adiposity. Finally, we demonstrate that the chemokine CCL2 contributes to microbiota-induced WAT inflammation in lard-fed mice. These results indicate that gut microbiota exacerbates metabolic inflammation through TLR signaling upon challenge with a diet rich in saturated lipids.
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•The gut microbiota contributes to phenotypic differences in mice fed lard or fish oil•Mice lacking MyD88 or TRIF are protected against WAT inflammation•Microbial-derived factors induce CCL2 in adipocytes through TLR4, MyD88, and TRIF•Microbial-induced CCL2 enhances macrophage accumulation in WAT
Caesar et al. reveal how saturated lipids in lard affect gut microbial composition to promote obesity and WAT inflammation via TLR signaling and CCL2; in contrast, mice fed a fish-oil diet enriched in polyunsaturated fatty acids are protected. Transfer of microbiota from fish-oil-fed mice dampens lard-induced inflammation.
Recent findings have demonstrated that the gut microbiome complements our human genome with at least 100-fold more genes. In contrast to our Homo sapiens-derived genes, the microbiome is much more ...plastic, and its composition changes with age and diet, among other factors. An altered gut microbiota has been associated with several diseases, including obesity and diabetes, but the mechanisms involved remain elusive. Here we discuss factors that affect the gut microbiome, how the gut microbiome may contribute to metabolic diseases, and how to study the gut microbiome. Next-generation sequencing and development of software packages have led to the development of large-scale sequencing efforts to catalog the human microbiome. Furthermore, the use of genetically engineered gnotobiotic mouse models may increase our understanding of mechanisms by which the gut microbiome modulates host metabolism. A combination of classical microbiology, sequencing, and animal experiments may provide further insights into how the gut microbiota affect host metabolism and physiology.
The link between the gut microbiota and type 2 diabetes (T2D) warrants further investigation because of known confounding effects from antidiabetic treatment. Here, we profiled the gut microbiota in ...a discovery (n = 1,011) and validation (n = 484) cohort comprising Swedish subjects naive for diabetes treatment and grouped by glycemic status. We observed that overall gut microbiota composition was altered in groups with impaired glucose tolerance, combined glucose intolerance and T2D, but not in those with impaired fasting glucose. In addition, the abundance of several butyrate producers and functional potential for butyrate production were decreased both in prediabetes and T2D groups. Multivariate analyses and machine learning microbiome models indicated that insulin resistance was strongly associated with microbial variations. Therefore, our study indicates that the gut microbiota represents an important modifiable factor to consider when developing precision medicine approaches for the prevention and/or delay of T2D.
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•The overall gut microbiota shifts in parallel with glycemic status in humans•The shifts are observed in the absence of diabetes treatment•The variations strongly associate with insulin resistance, but not fasting glucose•Butyrate-producing bacteria are reduced in prediabetes and type 2 diabetes
Type 2 diabetes is associated with an altered gut microbiota, but the results may have been confounded by metformin medication. Wu et al. now use two populations encompassing almost 1,500 subjects to demonstrate that the gut microbiota is altered in prediabetes and diabetes independent of diabetes medication.
Microbial amplicon sequencing studies are an important tool in biological and biomedical research. Widespread 16S rRNA gene microbial surveys have shed light on the structure of many ecosystems ...inhabited by bacteria, including the human body. However, specialized software and algorithms are needed to convert raw sequencing data into biologically meaningful information (i.e. tables of bacterial counts). While different bioinformatic pipelines are available in a rapidly changing and improving field, users are often unaware of limitations and biases associated with individual pipelines and there is a lack of agreement regarding best practices. Here, we compared six bioinformatic pipelines for the analysis of amplicon sequence data: three OTU-level flows (QIIME-uclust, MOTHUR, and USEARCH-UPARSE) and three ASV-level (DADA2, Qiime2-Deblur, and USEARCH-UNOISE3). We tested workflows with different quality control options, clustering algorithms, and cutoff parameters on a mock community as well as on a large (N = 2170) recently published fecal sample dataset from the multi-ethnic HELIUS study. We assessed the sensitivity, specificity, and degree of consensus of the different outputs. DADA2 offered the best sensitivity, at the expense of decreased specificity compared to USEARCH-UNOISE3 and Qiime2-Deblur. USEARCH-UNOISE3 showed the best balance between resolution and specificity. OTU-level USEARCH-UPARSE and MOTHUR performed well, but with lower specificity than ASV-level pipelines. QIIME-uclust produced large number of spurious OTUs as well as inflated alpha-diversity measures and should be avoided in future studies. This study provides guidance for researchers using amplicon sequencing to gain biological insights.
Bariatric surgery is currently the most effective procedure for the treatment of obesity. Given the role of the gut microbiota in regulating host metabolism and adiposity, we investigated the ...long-term effects of bariatric surgery on the microbiome of patients randomized to Roux-en-Y gastric bypass or vertical banded gastroplasty and matched for weight and fat mass loss. The two surgical procedures induced similar and durable changes on the gut microbiome that were not dependent on body mass index and resulted in altered levels of fecal and circulating metabolites compared with obese controls. By colonizing germ-free mice with stools from the patients, we demonstrated that the surgically altered microbiota promoted reduced fat deposition in recipient mice. These mice also had a lower respiratory quotient, indicating decreased utilization of carbohydrates as fuel. Our results suggest that the gut microbiota may play a direct role in the reduction of adiposity observed after bariatric surgery.
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•RYGB and VBG induce long-term alterations in the human gut microbiome•The changes in the microbiome do not depend on BMI•RYGB and VBG have different effects on bile acid and TMAO metabolism•The surgically altered microbiome contributes to fat mass regulation
Bariatric surgery durably alters the human gut microbiome. Here, Tremaroli et al. demonstrate that two types of bariatric surgery, Roux-en-Y gastric bypass and vertical banded gastroplasty, produce long-term alterations of the gut microbiome independently of BMI and that these alterations modulate host metabolism and fat mass deposition.
The gut is inhabited by a densely populated ecosystem, the gut microbiota, that is established at birth. However, the succession by which different bacteria are incorporated into the gut microbiota ...is still relatively unknown. Here, we analyze the microbiota from 471 Swedish children followed from birth to 5 years of age, collecting samples after 4 and 12 months and at 3 and 5 years of age as well as from their mothers at birth using 16S rRNA gene profiling. We also compare their microbiota to an adult Swedish population. Genera follow 4 different colonization patterns during establishment where Methanobrevibacter and Christensenellaceae colonize late and do not reached adult levels at 5 years. These late colonizers correlate with increased alpha diversity in both children and adults. By following the children through age-specific community types, we observe that children have individual dynamics in the gut microbiota development trajectory.
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For a Figure360 author presentation of this figure, see https://doi.org/10.1016/j.chom.2021.02.021
•Children gut microbiota mature along similar trajectories but at different speeds•Different microbes follow discrete trajectories in the developing gut microbiota•The effect of c-section on gut microbiota is normalized in 3–5-year-old children•The gut microbiota has not yet reached adult complexity in 5-years-old children
Roswall et al. show in a longitudinal birth cohort with 471 children that the gut microbiota is still developing at 5 years, when microbes associated with high community richness are acquired. The individual dynamics of the gut microbiota may indicate sensitive points for gut microbiota development early in life.
The gut microbiota regulates bone mass in mice Sjögren, Klara; Engdahl, Cecilia; Henning, Petra ...
Journal of bone and mineral research,
June 2012, Letnik:
27, Številka:
6
Journal Article
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