Facultad de Medicina

Composition of the gut microbiota changes during ageing, but questions remain about whether age is also associated with deficits in microbiome function and whether these changes occur sharply or progressively. The ability to define these deficits in populations of different ages may help determine a chronological age threshold at which deficits occur and subsequently identify innovative dietary strategies for active and healthy ageing. Here, active gut microbiota and associated metabolic functions were evaluated using shotgun proteomics in three well‐defined age groups consisting of 30 healthy volunteers, namely, ten infants, ten adults and ten elderly individuals. Samples from each volunteer at intervals of up to 6 months (n = 83 samples) were used for validation. Ageing gradually increases the diversity of gut bacteria that actively synthesize proteins, that is by 1.4‐fold from infants to elderly individuals. An analysis of functional deficits consistently identifies a relationship between tryptophan and indole metabolism and ageing (p < 2.8e−8). Indeed, the synthesis of proteins involved in tryptophan and indole production and the faecal concentrations of these metabolites are directly correlated (r2 > .987) and progressively decrease with age (r2 > .948). An age threshold for a 50% decrease is observed ca. 11–31 years old, and a greater than 90% reduction is observed from the ages of 34–54 years. Based on recent investigations linking tryptophan with abundance of indole and other “healthy” longevity molecules and on the results from this small cohort study, dietary interventions aimed at manipulating tryptophan deficits since a relatively “young” age of 34 and, particularly, in the elderly are recommended.

Obesity has reached an epidemic level worldwide, and bariatric surgery (BS) has been proven to be the most efficient therapy to reduce severe obesity-related comorbidities. Given that the gut microbiota plays a causal role in obesity development and that surgery may alter the gut environment, investigating the impact of BS on the microbiota in the context of severe obesity is important. Although, alterations at the level of total gut bacteria, total gene content and total metabolite content have started to be disentangled, a clear deficit exists regarding the analysis of the active fraction of the microbiota, which is the fraction that is most reactive to the BS. Here, active gut microbiota and associated metabolic functions were evaluated using shotgun proteomics and metabolomics in 40 severely obese volunteers. Samples from each volunteer were obtained under basal conditions, after a short high protein and calorie-restricted diet, and 1 and 3 months after BS, including laparoscopic surgery through Roux-en-Y Gastric Bypass or Sleeve Gastrectomy. The results revealed for the first time the most active microbes and metabolic flux distribution pre- and post-surgery and deciphered main differences in the way sugars and short-fatty acids are metabolized, demonstrating that less energy-generating and anaerobic metabolism and detoxification mechanisms are promoted post-surgery. A comparison with non-obese proteome data further signified different ways to metabolize sugars and produce short chain fatty acids and deficiencies in proteins involved in iron transport and metabolism in severely obese individuals compared to lean individuals.