Objective Ageing is accompanied by deterioration of multiple bodily functions and inflammation, which collectively contribute to frailty. We and others have shown that frailty co-varies with alterations in the gut microbiota in a manner accelerated by consumption of a restricted diversity diet. The Mediterranean diet (MedDiet) is associated with health. In the NU-AGE project, we investigated if a 1-year MedDiet intervention could alter the gut microbiota and reduce frailty. Design We profiled the gut microbiota in 612 non-frail or pre-frail subjects across five European countries (UK, France, Netherlands, Italy and Poland) before and after the administration of a 12-month long MedDiet intervention tailored to elderly subjects (NU-AGE diet). Results Adherence to the diet was associated with specific microbiome alterations. Taxa enriched by adherence to the diet were positively associated with several markers of lower frailty and improved cognitive function, and negatively associated with inflammatory markers including C-reactive protein and interleukin-17. Analysis of the inferred microbial metabolite profiles indicated that the diet-modulated microbiome change was associated with an increase in short/branch chained fatty acid production and lower production of secondary bile acids, p-cresols, ethanol and carbon dioxide. Microbiome ecosystem network analysis showed that the bacterial taxa that responded positively to the MedDiet intervention occupy keystone interaction positions, whereas frailty-associated taxa are peripheral in the networks. Conclusion Collectively, our findings support the feasibility of improving the habitual diet to modulate the gut microbiota which in turn has the potential to promote healthier ageing.

Characterizing the taxonomic diversity of microbial communities is one of the primary objectives of metagenomic studies. Taxonomic analysis of microbial communities, a process referred to as binning, is challenging for the following reasons. Primarily, query sequences originating from the genomes of most microbes in an environmental sample lack taxonomically related sequences in existing reference databases. This absence of a taxonomic context makes binning a very challenging task. Limitations of current sequencing platforms, with respect to short read lengths and sequencing errors/artifacts, are also key factors that determine the overall binning efficiency. Furthermore, the sheer volume of metagenomic datasets also demands highly efficient algorithms that can operate within reasonable requirements of compute power. This review discusses the premise, methodologies, advantages, limitations and challenges of various methods available for binning of metagenomic datasets obtained using the shotgun sequencing approach. Various parameters as well as strategies used for evaluating binning efficiency are then reviewed.

Interaction between disease-microbiome associations and ageing has not been explored in detail. Here, using age/region-matched sub-sets, we analysed the gut microbiome differences across five major diseases in a multi-cohort dataset constituting more than 2500 individuals from 20 to 89 years old. We show that disease-microbiome associations display specific age-centric trends. Ageing-associated microbiome alterations towards a disease-like configuration occur in colorectal cancer patients, thereby masking disease signatures. We identified a microbiome disease response shared across multiple diseases in elderly subjects that is distinct from that in young/middle-aged individuals, but also a novel set of taxa consistently gained in disease across all age groups. A subset of these taxa was associated with increased frailty in subjects from the ELDERMET cohort. The relevant taxa differentially encode specific functions that are known to have disease associations.

Malnutrition is a global health problem affecting more than 300 million pre-school children worldwide. It is one of the major health concerns in India since around 50% of children below the age of two suffer from various forms of malnutrition. The gut microbiome plays an important role in nutrient pre-processing, assimilation and energy harvest from food. Consequently, dysbiosis of the gut microbiota has been implicated in malnutrition. Metagenomics approach was adopted to investigate the gut microbiome sampled from 20 rural Indian children with varying nutritional status. The changes in the abundances of various taxonomic and functional groups were investigated across these gut microbiomes. A core set of 23 genera were observed across samples, with some showing differential abundances with varying nutritional status. One of the findings of the current study is the positive/negative associations of specific taxonomic and functional groups with the nutritional status of the children. Notable alterations in the architecture of the inter-microbial co-occurrence networks were also observed with changes in nutritional status. A key example is the clustering of potentially pathogenic groups into a distinct hub in severely malnourished gut. Our data does not demonstrate causality with the microbiome patterns that we observed, rather a description of some interesting patterns, whose underlying mechanism remains to be uncovered. The present study envisioned interrelationships between the pattern of gut microbiome and the nutritional status of children. The cause of this pattern needs to be explored. However, insights obtained from the present study form the basis for further metagenomic investigations on larger population of children. Results of such studies will be useful in identifying the key microbial groups that can be utilized for targeted therapeutic interventions for managing severe acute malnutrition.