Another Mendelian study finding no gut microbiome => chronic disease etc causal links

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Eddy Edson

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Relationship to Diabetes
Type 2
There have been a number of these Mendelian randomisation studies recently testing whether the observational associations seen in some studies have a causal basis, and finding little. The microbiome field seems way over-hyped.


Abstract

Features of the gut microbiota have been associated with several chronic diseases and longevity in preclinical models as well as in observational studies. Whether these relations underlie causal effects in humans remains to be established.

We aimed to determine whether the gut microbiota influences cardiometabolic traits as well as the risk of chronic diseases and human longevity using a comprehensive 2-Sample Mendelian randomization approach. We included as exposures 10 gut-associated metabolites and pathways and 57 microbial taxa abundance. We included as outcomes nine cardiometabolic traits (fasting glucose, fasting insulin, systolic blood pressure, diastolic blood pressure, HDL cholesterol, LDL cholesterol, triglycerides, estimated glomerular filtration rate, body mass index [BMI]), eight chronic diseases previously linked with the gut microbiota in observational studies (Alzheimer’s disease, depression, type 2 diabetes, non-alcoholic fatty liver disease, coronary artery disease (CAD), stroke, osteoporosis and chronic kidney disease), as well as parental lifespan and longevity.

We found 7 associations with evidence of causality before and after sensitivity analyses, but not after multiple testing correction (1198 tests). Most effect sizes (4/7) were small. The two largest exposure-outcome effects were markedly attenuated towards the null upon inclusion of BMI or alcohol intake frequency in multivariable MR analyses.

While finding robust genetic instruments for microbiota features is challenging hence potentially inflating type 2 errors, these results do not support a large causal impact of human gut microbita features on cardiometabolic traits, chronic diseases or longevity. These results also suggest that the previously documented associations between gut microbiota and human health outcomes may not always underly causal relations.
 
Interesting that the observed associations aren’t being strengthened with a bit more digging.

I liked the biome thing as a way of explaining why 2 different people eating the same food can have such different glucose responses (which we see in people’s experiences here all the time).

I guess it must be something else in the weird science-fog that is biology, metabolism and digestion o_O
 
There goes Prof Tim Spector's career...
 
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