Abstract

The effect of calorie restriction (CR) on the microbiome, fecal metabolome, and colon transcriptome of adult and old male mice was compared. Life-long CR increased microbial diversity and the Bacteroidetes/Firmicutes ratio and prevented the age-related changes in the microbiota, shifting it to a younger microbial and fecal metabolite profile in both C57BL/6JN and B6D2F1 mice. Old mice fed CR were enriched in the Rikenellaceae, S24-7 and Bacteroides families. The changes in the microbiome that occur with age and CR were initiated in the cecum and further modified in the colon. Short-term CR in adult mice had a minor effect on the microbiome but a major effect on the transcriptome of the colon mucosa. These data suggest that CR has a major impact on the physiological status of the gastrointestinal system, maintaining it in a more youthful state, which in turn could result in a more diverse and youthful microbiome.

Highlights

  • The first and the most studied manipulation shown to increase lifespan in mammals is caloric restriction (CR)

  • Using male mice obtained from the aging colony maintained by the NIA, we studied the microbiota composition of the cecum and colon of 9- and 24-month old male C57BL/6JN mice fed AL or calorie restriction (CR) by sequencing the V4 region of the bacterial 16S rRNA gene

  • Adult B6D2F1 were not available from the NIA; we were only able to measure the microbiome of the cecum and colon of 24month-old B6D2F1 mice fed either AL or CR, and these data are presented in Table 3S in the supplement

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Summary

Introduction

The first and the most studied manipulation shown to increase lifespan in mammals is caloric restriction (CR). Panels E and F show PCA plots of the microbiome from the cecum and colon, respectively for old C57BL/6JN and B6D2F1 mice fed AL and CR.

Results
Conclusion

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