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Early-life effects of juvenile Western diet and exercise on adult gut microbiome composition in mice

McNamara M, Singleton J, Cadney M, Ruegger P, Borneman J, Garland T (2021) Journal of Experimental Biology doi: 10.1242/jeb.239699  

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Abstract:

Alterations to the gut microbiome caused by changes in diet, consumption of antibiotics, etc., can affect host function. Moreover, perturbation of the microbiome during critical developmental periods potentially have long-lasting impacts on hosts.

Using four selectively bred High Runner and four non-selected Control lines of mice, we examined the effects of early-life diet and exercise manipulations on the adult microbiome by sequencing the hypervariable Internal Transcribed Spacer region of the bacterial gut community. Mice from High Runner lines run ∼3-fold more on wheels than do Controls, and have several other phenotypic differences (e.g., higher food consumption and body temperature) that could alter the microbiome, either acutely or in terms of coevolution. Males from generation 76 were given wheels and/or Western diet from weaning until sexual maturity at 6 weeks of age, then housed individually without wheels on standard diet until 14 weeks of age, when fecal samples were taken.

Juvenile Western diet reduced bacterial richness and diversity after the 8-week washout period (equivalent to ∼6 human years). We also found interactive effects of genetic linetype, juvenile diet, and/or juvenile exercise on microbiome composition and diversity. Microbial community structure clustered significantly in relation to both linetype and diet. Western diet also reduced the relative abundance of 
Muribaculum intestinale.

These results constitute one of the first reports of juvenile diet having long-lasting effects on the adult microbiome after a substantial washout period. Moreover, we found interactive effects of diet with early-life exercise exposure, and a dependence of these effects on genetic background.

FAB RESEARCH COMMENT:

This animal study shows long-term effects on the gut microbiota from consuming a typical western-type diet (high in both sugar and fat) during childhood. 

Bacterial richness and diversity was significantly reduced by this diet - which was fed from weaning until sexual maturity - and although a normal, healthier diet was then fed to the animals, these changes to the gut microbiota were still apparent the equivalent of six human years later. 

Both exercise and genetic factors were also shown to interact with diet to influence gut microbial composition.

These data show the importance of infancy and childhood as critical developmental periods for the establishment of the gut microbiome, with negative effects of diet during this time persisting well into adulthood.

While generalisability from animal studies to humans can never be assumed, these findings add to the already substantial evidence from human studies that early life nutrition can have significant effects on health in later life.

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