Association of Insulin Resistance and Type 2 Diabetes With Gut Microbial Diversity

Chen, Zhangling; Radjabzadeh, Djawad; Chen, Lianmin; Kurilshikov, Alexander; Kavousi, Maryam; Ahmadizar, Fariba; Ikram, M. Arfan; Uitterlinden, André G.; Zhernakova, Alexandra; Fu, Jingyuan; Kraaij, Robert; Voortman, Trudy

doi:10.1001/jamanetworkopen.2021.18811

Cited by 179 publications

(134 citation statements)

References 26 publications

Supporting

Mentioning

105

Contrasting

Unclassified

Order By: Relevance

“…In both diabetes and hyperlipidemia, Faith's PD values were lower than in those without these disorders. These findings recapitulate previous reports [44][45][46][47][48][49]. Whether these are causal links is not known.…”

Section: Discussionsupporting

confidence: 90%

Markers of Gut Barrier Function and Microbial Translocation Associate with Lower Gut Microbial Diversity in People with HIV

Ellis

Iudicello

Heaton

et al. 2021

Viruses

View full text Add to dashboard Cite

People with human immunodeficiency virus (HIV) (PWH) have reduced gut barrier integrity (“leaky gut”) that permits diffusion of microbial antigens (microbial translocation) such as lipopolysaccharide (LPS) into the circulation, stimulating inflammation. A potential source of this disturbance, in addition to gut lymphoid tissue CD4+ T-cell depletion, is the interaction between the gut barrier and gut microbes themselves. We evaluated the relationship of gut barrier integrity, as indexed by plasma occludin levels (higher levels corresponding to greater loss of occludin from the gut barrier), to gut microbial diversity. PWH and people without HIV (PWoH) participants were recruited from community sources and provided stool, and 16S rRNA amplicon sequencing was used to characterize the gut microbiome. Microbial diversity was indexed by Faith’s phylogenetic diversity (PD). Participants were 50 PWH and 52 PWoH individuals, mean ± SD age 45.6 ± 14.5 years, 28 (27.5%) women, 50 (49.0%) non-white race/ethnicity. PWH had higher gut microbial diversity (Faith’s PD 14.2 ± 4.06 versus 11.7 ± 3.27; p = 0.0007), but occludin levels were not different (1.84 ± 0.311 versus 1.85 ± 0.274; p = 0.843). Lower gut microbial diversity was associated with higher plasma occludin levels in PWH (r = −0.251; p = 0.0111), but not in PWoH. A multivariable model demonstrated an interaction (p = 0.0459) such that the correlation between Faith’s PD and plasma occludin held only for PWH (r = −0.434; p = 0.0017), but not for PWoH individuals (r = −0.0227; p = 0.873). The pattern was similar for Shannon alpha diversity. Antiretroviral treatment and viral suppression status were not associated with gut microbial diversity (ps > 0.10). Plasma occludin levels were not significantly related to age, sex or ethnicity, nor to current or nadir CD4 or plasma viral load. Higher occludin levels were associated with higher plasma sCD14 and LPS, both markers of microbial translocation. Together, the findings suggest that damage to the gut epithelial barrier is an important mediator of microbial translocation and inflammation in PWH, and that reduced gut microbiome diversity may have an important role.

show abstract

Section: Discussionsupporting

confidence: 90%

Markers of Gut Barrier Function and Microbial Translocation Associate with Lower Gut Microbial Diversity in People with HIV

Ellis

Iudicello

Heaton

et al. 2021

Viruses

View full text Add to dashboard Cite

show abstract

“…A metagenome-wide association study (MGWAS) indicated that T2DM patients were accompanied by moderate degree of gut microbiome dysbiosis and the gut microbial markers might help classify T2DM (29). In addition, compared with participants without diabetes, patients with T2DM had a lower richness of gut microbiome (30). The mathematical model of the metagenomic profiles established based on the gut microbiome could identify T2DM with high accuracy (31).…”

Section: Discussionmentioning

confidence: 99%

Genetically Predicted Causality of 28 Gut Microbiome Families and Type 2 Diabetes Mellitus Risk

Xiang

Zhang

et al. 2022

Front. Endocrinol.

View full text Add to dashboard Cite

Mounting evidence indicates that gut microbiome may be involved in the pathogenesis of type 2 diabetes mellitus (T2DM). However, there is no consensus on whether there is a causal link between gut microbiome and T2DM risk. In the present study, the Mendelian randomization (MR) analysis was performed to investigate whether gut microbiome was causally linked to T2DM risk. The single nucleotide polymorphisms (SNPs) that were significantly related to exposure from published available genome-wide association study (GWAS) were selected as instrumental variables (IVs). The robust methods including inverse variance weighting (IVW), MR Egger, and weighted median were conducted to infer the causal links. Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and MR-Egger regression were used to test whether there was horizontal pleiotropy and identify outlier SNPs. The estimates of IVW suggested that Streptococcaceae (odds ratio (OR) = 1.17, 95% confidence interval (CI), 1.04–1.31, p = 0.009) was associated with higher risk of T2DM in European population. In Asian population, the MR IVW estimates revealed that there was a causal link between Acidaminococcaceae and T2DM risk (OR = 1.17, 95% CI, 1.04–1.31, p = 0.008). There was no evidence of notable heterogeneity and horizontal pleiotropy. However, after false discovery rate (FDR) correction, the causal link between gut microbiome and T2DM was absent (FDR, p > 0.05). In summary, using genetic instruments, this study does not find evidence of association between the 28 gut microbiome families and T2DM risk. However, Streptococcaceae and Acidaminococcaceae may have a borderline positive correlation with T2DM risk.

show abstract

“…Dietary fiber intake was also associated with less weight gain. Another study found that higher α diversity in the gut microbiome, along with more butyrate-producing species, were associated with a lower incidence of type 2 diabetes and lower rates of insulin resistance among non-diabetic individuals [48]. Therefore, we consider the increase in the Simpson diversity index observed with the test products in this in vitro model to be encouraging regarding their potential to impart beneficial effects on the human gut.…”

Section: Discussionmentioning

confidence: 75%

Evaluation of the Effect of Food Products Containing Prebiotics and Bacillus subtilis HU58 on the Gut Microbial Community Activity and Community Composition Using an In Vitro M-SHIME® Model

Marzorati

Bubeck²,

Bayne³

et al. 2021

Applied Sciences

View full text Add to dashboard Cite

GoodBiome™ Foods is a collection of foods infused with prebiotics, including inulin and xylooligosaccharides, and the probiotic Bacillus subtilis HU58. The effects of repeated intake of three predigested GoodBiome™ Foods products and one comparator product on microbial community activity and composition were assessed using the mucosal simulator of the human intestinal microbial system (M-SHIME®) platform with proximal colon (PC) and distal colon (DC) compartments and conducted under healthy gut conditions. Treatment with all test products increased short-chain fatty acid (SCFA) production (acetate, propionate, and butyrate) versus the control period in both the PC and DC. The highest increases were seen with the GoodBiome™ Foods products. Ammonium and branched SCFA levels were also increased (versus the control period) in both compartments. Treatment with all test products enhanced the Simpson diversity index (versus the control period), reaching significance for all test products in the PC (p < 0.05). Treatment with all test products resulted in changes in the microbial community composition. The relative abundance increased for Proteobacteria and decreased for Actinobacteria in the PC and DC. Repeated intake of GoodBiome™ Food products increased SCFA production and microbial diversity in an M-SHIME® model of the human intestinal microbiome.

show abstract

Association of Insulin Resistance and Type 2 Diabetes With Gut Microbial Diversity

Cited by 179 publications

References 26 publications

Markers of Gut Barrier Function and Microbial Translocation Associate with Lower Gut Microbial Diversity in People with HIV

Markers of Gut Barrier Function and Microbial Translocation Associate with Lower Gut Microbial Diversity in People with HIV

Genetically Predicted Causality of 28 Gut Microbiome Families and Type 2 Diabetes Mellitus Risk

Evaluation of the Effect of Food Products Containing Prebiotics and Bacillus subtilis HU58 on the Gut Microbial Community Activity and Community Composition Using an In Vitro M-SHIME® Model

Contact Info

Product

Resources

About