Mendelian randomization analyses support causal relationship between gut microbiota and childhood obesity

Abstract

BackgroundChildhood obesity (CO) is an increasing public health issue. Mounting evidence has shown that gut microbiota (GM) is closely related to CO. However, the causal association needs to be treated with caution due to confounding factors and reverse causation.MethodsData were obtained from the Microbiome Genome Consortium for GM as well as the Early Growth Genetics Consortium for childhood obesity and childhood body mass index (CBMI). Inverse variance weighted, maximum likelihood, weighted median, and MR.RAPS methods were applied to examine the causal association. Then replication dataset was used to validate the results and reverse Mendelian randomization analysis was performed to confirm the causal direction. Additionally, sensitivity analyses including Cochran's Q statistics, MR-Egger intercept, MR-PRESSO global test, and the leave-one-out analysis were conducted to detect the potential heterogeneity and horizontal pleiotropy.ResultsOur study found suggestive causal relationships between eight bacterial genera and the risk of childhood obesity (five for CO and four for CBMI). After validating the results in the replication dataset, we finally identified three childhood obesity-related GM including the genera Akkermansia, Intestinibacter, and Butyricimonas. Amongst these, the genus Akkermansia was both negatively associated with the risk of CO (OR = 0.574; 95% CI: 0.417, 0.789) and CBMI (β = −0.172; 95% CI: −0.306, −0.039).ConclusionsIn this study, we employed the MR approach to investigate the causal relationship between GM and CO, and discovered that the genus Akkermansia has a protective effect on both childhood obesity and BMI. Our findings may provide a potential strategy for preventing and intervening in CO, while also offering novel insights into the pathogenesis of CO from the perspective of GM.

Gut microbiota-metabolite interactions meditate the effect of dietary patterns on precocious puberty

“… 56 , 57 Mendelian randomization analyses confirmed the causal relationship between increased Romboutsia and decreased risk of childhood obesity. 58 Blautia has the potential to reduce HFD-induced obesity and insulin resistance among rats. 59 , 60 Among the major metabolites contributing to Factor 2, p -coumaric acid and 2-amino-8-oxo-9,10-epoxy-decanoic acid are also involved in maintaining a healthy weight.…”

Unraveling the mystery: a Mendelian randomized exploration of gut microbiota and different types of obesity

“…Li et al. observed that the genus Akkermansia exhibited a protective effect against childhood obesity and BMI ( Li et al., 2023 ). There are several potential mechanisms underlying the association between the gut microbiota and obesity: The gut microbial community enhances energy intake from food by producing efficient enzymes for the degradation of dietary nutrients ( Blaut, 2015 ).…”

“…Bäckhed et al transplanted the gut microbiota of normal mice into germ-free mice, resulting in a significant increase in body fat percentage even without altering food intake (Backhed et al, 2004). Li et al observed that the genus Akkermansia exhibited a protective effect against childhood obesity and BMI (Li et al, 2023). There are several potential mechanisms underlying the association between the gut microbiota and obesity: The gut microbial community enhances energy intake from food by producing efficient enzymes for the degradation of dietary nutrients (Blaut, 2015).…”

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“…Previous studies have employed MR analysis to investigate the causal association between gut microbiota and childhood obesity 14 and abdominal obesity. 15 Moreover, because of the association between obesity and other diseases, studies have reported a relationship between BFP and other diseases.…”