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Age-associated signatures in the composition and pro-inflammatory status of the gut microbiome in humans and mice, and the impact of a periodic fasting intervention to promote healthy aging

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Gut inflammation in the elderly

An imbalance in the human gut microbiome can affect the interplay with the host immune system and lead to a variety of diseases. Targeting the microbiome via diet and probiotics could promote well-being.

Fundamental Research

Accumulating evidence indicates that many people develop low-grade chronic inflammation with age. This unfortunately contributes to the development of associated diseases such as metabolic disorders and neurodegeneration. However, despite intensive research, the factors that drive age-associated inflammation are still poorly understood. Scientists of the EU-funded Gut-InflammAge project worked under the hypothesis that age-related inflammation is linked to gut microbiome composition or its immune-modulating potential. An unusual composition of gut microbes, known as microbiota dysbiosis, has been known to promote intestinal inflammation in patients with inflammatory bowel disease but no association has been made with ageing. Microbiota analyses To investigate this issue, researchers performed a microbiota analysis in young and aged healthy Danish individuals. They used faecal samples collected from a study that focused on functional disorders in the area around Copenhagen during 2013-2016. Samples were selected based on strict health criteria using clinical parameters of metabolic, kidney, and liver function as well as a normal body mass index. Researchers combined high-throughput sequencing, bioinformatics and analysis of the immunoglobulin A (IgA)-coated microbes. IgA is a key antibody used by the intestinal immune system to protect the gut barrier against invading microbes. IgA-coated microbes served as a marker of inflammation for this study as well as the gut microbiota composition. “We wanted to test whether these two biomarkers would reveal signs of increased intestinal inflammation in the aged individuals,″ explains the Marie Curie research fellow Dr Thorsten Brach who performed all the work. In this context, they used flow cytometry to determine the proportion of microbes that are highly coated by IgA, and sequencing to determine the microbial species in each case. Sequencing information enabled taxonomic characterisation of the microbiota composition and unveiled significant differences between the old and young group with particular microbe families being more abundant in older individuals. Importantly, the proportion of highly-IgA coated microbes was generally low and no differences were observed between the groups. Diet to modulate microbiota composition Many healthy-aging interventions rely on diets that impose permanent calorie restriction without malnutrition and promote longevity. As this approach is difficult to follow, periodic fasting schemes have been employed for similar health benefits. Using a mouse model system, project scientists explored whether a periodic fasting scheme could promote gut microbiome modulations and metabolic health benefits. Experimental animals underwent periodic fasting from 8.5 to 14.5 months of age (equivalent to 35-50 years in humans) with 50 % calorie intake reduction. Interestingly, mice that fasted accumulated more body fat than the control mice but exhibited a mild rejuvenation of their blood profile. Clinical implications Overall, the small microbiota composition differences observed between the old and young individuals during Gut-InflammAge support the growing consensus that such variability is to be expected in metabolically healthy people. Project coordinator Prof. Manimozhiyan Arumugam believes that “diet and lifestyle are more critical factors in shaping the microbiota than age.″ At the same time, he emphasises that “with regards to diagnosis and therapy, it is very important to define a healthy range of microbiota compositions to know what to strive for when treating patients with actual dysbiosis.″ With the continuous rise in the elderly population over the next years and the socioeconomic importance of healthy ageing, utilising antibody-coated microbes as a sign of intestinal inflammation could be used for diagnostic purposes.


Gut-InflammAge, inflammation, IgA, diet, gut microbiota

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