The gut is home to trillions of microorganisms that have fundamental roles in many aspects of human biology, including immune function and metabolism1,2. The reduced diversity of the gut microbiota in Western populations compared to that in populations living traditional lifestyles presents the question of which factors have driven microbiota change during modernization. Microbiota-accessible carbohydrates (MACs) found in dietary fibre have a crucial involvement in shaping this microbial ecosystem, and are notably reduced in the Western diet (high in fat and simple carbohydrates, low in fibre) compared with a more traditional diet3. Here we show that changes in the microbiota of mice consuming a low-MAC diet and harbouring a human microbiota are largely reversible within a single generation. However, over several generations, a low-MAC diet results in a progressive loss of diversity, which is not recoverable after the reintroduction of dietary MACs. To restore the microbiota to its original state requires the administration of missing taxa in combination with dietary MAC consumption. Our data illustrate that taxa driven to low abundance when dietary MACs are scarce are inefficiently transferred to the next generation, and are at increased risk of becoming extinct within an isolated population. As more diseases are linked to the Western microbiota and the microbiota is targeted therapeutically, microbiota reprogramming may need to involve strategies that incorporate dietary MACs as well as taxa not currently present in the Western gut.
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Sequence Read Archive
The 16S sequence data have been deposited in the Sequence Read Archive (SRA) under the accession PRJNA303185.
We thank M. St. Onge for technical assistance. This work was funded by a grant from National Institutes of Health NIDDK (R01-DK085025 to J.L.S.), an NSF graduate fellowship (to S.A.S.), a Stanford Graduate Fellowship (to S.A.S.), and the Simons Foundation (to M.T.). J.L.S. holds an Investigators in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund.
A table of high-confidence OTUs that dropped in abundance by at least two-fold in the first generation diet-switching mice after switch to the low-MAC diet and the control high-MAC diet mice.
A table of high-confidence OTUs that dropped in abundance by at least two-fold in the first generation diet-switching mice after return to the high-MAC diet and the control high-MAC diet mice.
A table of high-confidence OTUs lost through generation four while consuming the low MAC diet and after switch to the high MAC diet.
A comparison of glycoside hydrolases from metagenomic data and imputed from 16S rRNA amplicon sequencing data.
Table of fold change of glycoside hydrolase families from generation one to generation four in the diet-switching and control groups.
Table of unique glycoside hydrolase sub-families in diet-switching mice between generations one and four by sampling depth.
Table of low abundance taxa that were passed or not passed between each of four generations of mice.
Table of number of high-confidence sub-OTUs present at the start of the experiment and the number of high-confidence sub-OTUs lost by the fourth generation and between the third and fourth generation.
Table of high-confidence OTUs that were no longer detectable after four generations on the low MAC and return after FMT.
Table of high-confidence sub-OTUs that were no longer detectable after four generations on the low MAC and return after FMT.