Research Article: Functional metagenomic profiling of intestinal microbiome in extreme ageing

Date Published: December 10, 2013

Publisher: Impact Journals LLC

Author(s): Simone Rampelli, Marco Candela, Silvia Turroni, Elena Biagi, Sebastiano Collino, Claudio Franceschi, Paul W O’Toole, Patrizia Brigidi.

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Abstract

Age-related alterations in human gut microbiota composition have been thoroughly described, but a detailed functional description of the intestinal bacterial coding capacity is still missing. In order to elucidate the contribution of the gut metagenome to the complex mosaic of human longevity, we applied shotgun sequencing to total fecal bacterial DNA in a selection of samples belonging to a well-characterized human ageing cohort. The age-related trajectory of the human gut microbiome was characterized by loss of genes for shortchain fatty acid production and an overall decrease in the saccharolytic potential, while proteolytic functions were more abundant than in the intestinal metagenome of younger adults. This altered functional profile was associated with a relevant enrichment in “pathobionts”, i.e. opportunistic pro-inflammatory bacteria generally present in the adult gut ecosystem in low numbers. Finally, as a signature for long life we identified 116 microbial genes that significantly correlated with ageing. Collectively, our data emphasize the relationship between intestinal bacteria and human metabolism, by detailing the modifications in the gut microbiota as a consequence of and/or promoter of the physiological changes occurring in the human host upon ageing.

Partial Text

Ageing is a complex multifactorial process with a major impact on the human body [1]. The ageing process seriously affects the human gut microbiota in particular, because it is accompanied by changes in the physiology of the gastrointestinal tract and associated immune system, as well as by changes in diet and lifestyle [2,3]. The adult-like profile of the human intestinal microbiota is stably maintained over time in healthy adults [4,5], defining an essentially mutualistic scenario whereby, in return for a guaranteed nutrient supply, the gut microbiota provides numerous fundamental functions to the host, including vitamin and metabolite supply and colonization resistance against pathogens [6]. The pathophysiology of the ageing process can ultimately compromise this homeostasis with a subject-specific timing, depending on the individual physiological status, diet, lifestyle and frailty [7-13].

In the present study we characterized the gut microbiota metagenome of extreme longevity individuals, elderly people and a young adult by Illumina shotgun sequencing. The subjects chosen typify a bigger cohort whose members had been well characterized for gut microbiota composition as well as for urine and serum metabolites[8, 22]. Here we focused on the functional aspects of the gut microbiota, in order to investigate ageing-related changes of the microbiome structure and function. Confirming Biagi et al. (2010) [8], multivariate analysis of the taxonomic dataset showed an overall increase in Proteobacteria and a re-arrangement in Firmicutes in centenarians, whereas 70-year-old elderly people maintained a gut microbiota profile very similar to the one shown by the young adult. The Procrustes analysis highlighted the relationships between taxonomic and functional datasets, showing a clear separation between centenarians and younger subjects with respect to both microbiome structure and functionality. Shotgun sequencing analysis revealed important modifications in microbiota functions in centenarians, allowing us to define an aged-type microbiome characterized by a specific functional complement different from the one present in younger subjects. As a result of taxonomic rearrangements in the gut microbiota composition, the changes in microbiome structure we detected as a function of aging allowed us to shed some light on the mechanisms associated with bacterial community change accompanying the overall ageing process.

 

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