Gut Microbiota as a Trigger for Metabolic Inflammation in Obesity and Type 2 Diabetes

Scheithauer, Torsten P. M.; Rampanelli, Elena; Nieuwdorp, Max; Vallance, Bruce A.; Verchere, C. Bruce; Raalte, Daniël H. van; Herrema, Hilde

doi:10.3389/fimmu.2020.571731

Cited by 309 publications

(203 citation statements)

References 362 publications

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“…In adults, gut microbiota dysbiosis has been proposed as an etiologic factor underlying metabolic disease associated with IR, such as obesity and T2DM ( 3 – 6 ). To illustrate, following fecal microbiota transplantation from lean human donors to obese recipients with metabolic syndrome, a significant improvement in insulin sensitivity resulted ( 7 , 8 ).…”

Section: Introductionmentioning

confidence: 99%

Gut Microbiota of Chinese Obese Children and Adolescents With and Without Insulin Resistance

et al. 2021

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ObjectiveThe intestinal flora of gut microbiota in obese Chinese children and adolescents with and without insulin resistance (IR) was analyzed, as well as associations between the gut microbiota and two serum cytokines related to glucose metabolism, adropin and angiopoietin-like 4 (ANGPTL4).MethodsClinical data, fecal bacterial composition, glucose-related hormones, and serum adipokines (adropin and ANGPTL4) were analyzed in 65 Chinese children with exogenous obesity. The composition of the gut microbiota was determined by 16S rRNA-based metagenomics and IR was calculated using the homeostasis model assessment (HOMA).ResultsThe 65 obese subjects were divided into two groups: insulin sensitive (IS) (n=40, 57.5% males) or IR (n=25, 60% males). Principal coordinates analysis revealed that the gut microbiota samples from the IS group clustered together and separated partly from the IR group (p=0.008). By Mann-Whitney U-test, at a phylum level, a reduction of Firmicutes and an increase of Bacteroidetes in the IR subjects was observed. LEfSe analysis revealed that IS subject, when compared to their IR counterparts, harbored members of the order Coriobacteriales, Turicibacterales, Pasteurellales and family Turicibacteraceae, that were significantly more abundant. In contrast, the IR subjects had members of family Peptococcaceae that were significantly more prevalent than the IS subjects (all p<0.05). Spearman’s correlation analysis revealed that serum ANGPTL4 was positively associated with genus Bacteroides, Butyricimonas, and Alistipes, and adropin was positively associated with genus Anaerostipes and Alistipes, and negatively associated with genus Blautia (all p<0.05).ConclusionIn obese children, the gut microbiome in IR subjects was significantly discordant from the IS subjects, and the abundance of some metabolism-related bacteria correlated with the serum concentrations of adropin and ANGPTL4. These observations infer that the gut microbiota may be involved in the regulation of glucose metabolism in obesity.

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Section: Introductionmentioning

confidence: 99%

Gut Microbiota of Chinese Obese Children and Adolescents With and Without Insulin Resistance

et al. 2021

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“…This suggests that intestinal microorganism plays a certain regulatory role in the development of PCOS. Gut microbiota dysregulation could lead to insulin resistance by inducing inflammation, which is closely related to endometrium receptivity ( 8 , 23 ). These results suggested that the gut microbiota might influence the endometrium receptivity of PCOS through a potential mechanism.…”

Section: Introductionmentioning

confidence: 99%

β-Sitosterol Ameliorates Endometrium Receptivity in PCOS-Like Mice: The Mediation of Gut Microbiota

Cao

Huang

et al. 2021

Front. Nutr.

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Background: Polycystic ovary syndrome (PCOS), one of the most common endocrine diseases in women of childbearing age, has been found to be accompanied by changes in the gut microbiota. The Bu Shen Yang Xue formula (BSYXF) is a traditional Chinese medicine widely used for the treatment of PCOS. This study aimed to investigate whether the protective effects of β-sitosterol, the main active ingredient of BSYXF, on PCOS was mediated by regulating gut microbiota.Methods: The presence of β-sitosterol in BSYXF was detected by liquid chromatography-mass spectrometry. The PCOS-like mouse model was induced by dehydroepiandrosterone. The fecal supernatant of β-sitosterol-treated mice was prepared for fecal microbiota transplantation (FMT). Body weight and wet weight of the uterus and ovary of the mice were recorded for organ index calculation. Hematoxylin and eosin stain was used to assess the endometrial morphology and microenvironment changes. Expression of endometrial receptivity markers cyclooxygenase-2 (COX-2), Integrin ανβ3, leukemia inhibitory factor (LIF), and homeobox A10 (HOXA10) in the endometrium were determined by immunohistochemistry and western blot analysis. Enzyme-linked immunosorbent assay was employed to detect the expression of follicle stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), and testosterone (T) in the serum. The diversity of gut microbiota was examined by 16S rDNA gene sequencing.Results: With the treatment of β-sitosterol and β-sitosterol-FMT, the uterine index of PCOS-like mice increased, the ovarian index decreased, levels of COX-2, LH and T decreased, and levels of Integrin ανβ3, LIF, HOXA10, FSH, and P increased. Under β-sitosterol treatment, the structure of the gut microbiota in PCOS-like mice was also changed.Conclusion: β-sitosterol regulates the endometrial receptivity of PCOS and harmonizes the sex hormone balance, which may be related to the changes in the structure and composition of gut microbiota, thus affecting the pathological process of PCOS.

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“…It plays many specific functions, including maintenance of structural integrity of the gut mucosal barrier [ 9 ], development of the immune system [ 20 ], protection against enteric pathogens [ 21 ] and production of several nutrient-derived metabolites with potential to affect human metabolic function [ 22 ]. For these reasons, the alteration of microbial composition (known as dysbiosis) may lead to a pro-inflammatory state and the development of many pathologies including, gastrointestinal illnesses, metabolic diseases and brain disorders [ 23 , 24 , 25 , 26 ]. Recently, the connection between the brain and gut, the so-called gut–brain axis, has been involved in regulating feeding and appetite, glucose homeostasis and gut motility [ 27 ].…”

Section: Microbiota Immunity and Inflammationmentioning

confidence: 99%

“…Different studies comparing healthy controls with obese and diabetic patients have showed alterations at genus and phylum levels in their microbiome [ 25 ]. In particular, frequencies of Actinobacteria, Firmicutes or Proteobacteria phyla increased, whereas Bacteroidetes and Verrucomicrobia phyla decreased.…”

Section: Microbiota Immunity and Inflammationmentioning

confidence: 99%

Impact of Dietary Flavanols on Microbiota, Immunity and Inflammation in Metabolic Diseases

Martín

Ramos

2021

Nutrients

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Flavanols are natural occurring polyphenols abundant in fruits and vegetables to which have been attributed to beneficial effects on health, and also against metabolic diseases, such as diabetes, obesity and metabolic syndrome. These positive properties have been associated to the modulation of different molecular pathways, and importantly, to the regulation of immunological reactions (pro-inflammatory cytokines, chemokines, adhesion molecules, nuclear factor-κB [NF-κB], inducible enzymes), and the activity of cells of the immune system. In addition, flavanols can modulate the composition and function of gut microbiome in a prebiotic-like manner, resulting in the positive regulation of metabolic pathways and immune responses, and reduction of low-grade chronic inflammation. Moreover, the biotransformation of flavanols by gut bacteria increases their bioavailability generating a number of metabolites with potential to affect human metabolism, including during metabolic diseases. However, the exact mechanisms by which flavanols act on the microbiota and immune system to influence health and disease remain unclear, especially in humans where these connections have been scarcely explored. This review seeks to summarize recent advances on the complex interaction of flavanols with gut microbiota, immunity and inflammation focus on metabolic diseases.

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Gut Microbiota as a Trigger for Metabolic Inflammation in Obesity and Type 2 Diabetes

Cited by 309 publications

References 362 publications

Gut Microbiota of Chinese Obese Children and Adolescents With and Without Insulin Resistance

Gut Microbiota of Chinese Obese Children and Adolescents With and Without Insulin Resistance

β-Sitosterol Ameliorates Endometrium Receptivity in PCOS-Like Mice: The Mediation of Gut Microbiota

Impact of Dietary Flavanols on Microbiota, Immunity and Inflammation in Metabolic Diseases

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