Aging Resilience Through Microbiota Optimization and Regulation

Sarcopenia, characterized by the progressive loss of muscle mass and strength in older adults, is a key factor in health deterioration. It affects 15% of people between 65 and 80 years old and over 50% of those over 80, compromising autonomy and increasing the risk of diseases. Sarcopenia not only impacts muscle function but also bone health, mobility, and is associated with cardiometabolic diseases and cognitive decline. It has been proposed that changes in the gut microbiota in aging individuals, known as gut dysbiosis, contribute to sarcopenia. Species diversity decreases, and bacterial representation is altered, which could impair muscle function through various pathways, such as mitochondrial dysfunction, chronic inflammation, and disruption of protein synthesis. Muscle function loss is strongly associated with cognitive and metabolic impairment in older adults. Recently, it has been demonstrated that fecal microbiota transplantation (FMT) is an effective procedure for modulating gut microbiota and has proven highly effective in managing cases of Clostridium difficile-associated chronic diarrhea. The main objective of this project is to carry out FMT from young, physically active donors to a cohort of older adults to evaluate its effect on muscle, cognitive, and metabolic function. Why donors who exercise? There is growing evidence that gut microbiota diversity is increased in young, physically active individuals. The FMT is planned to be administered through lyophilized microbiota capsules. By restoring microbial diversity, it is expected to improve the quality and function of skeletal muscles, leading to greater cognitive and metabolic resilience. This project has great potential to develop an innovative approach for treating highly debilitating diseases that affect older adults, based on the lyophilization and encapsulation of gut microbiota from young, trained donors, which can be easily stored in a conventional freezer. Due to the high percentage of older adults worldwide and the high prevalence of sarcopenia within this age group, the aim of the project is to address a significant public health issue with a large target population eager for options to promote muscle health, functional autonomy, as well as cognitive and metabolic well-being.

Skeletal muscle loss in old age is a critical point for the development of very serious health conditions affecting the quality of life of older adults, such as loss of autonomy, loss of healthy cognition, and the development of complex metabolic diseases. Additionally, intestinal microbiota can be modulated through fecal microbiota transplantation (FMT), and possibly this modulation could have direct effects that promote muscle health. Therefore, this project aims to investigate whether modifying the intestinal microbiota in older adults through FMT using young and trained donors can enhance skeletal muscle health and function, leading to greater resilience, reducing cognitive decline, and metabolic dysfunction associated with aging, especially in stressful contexts. The donors would be young and trained individuals. Why trained donors? There is growing evidence that the composition of the intestinal microbiota is regulated by physical exercise. In animal studies, chronic exercise has been shown to increase the biodiversity of the intestinal microbiota and reduce systemic and intestinal inflammation. The bacterial profile associated with exercise is specific, for example, it does not correspond to that associated with a healthy diet, suggesting that physical activity allows for the development of a specific microbial profile in intestinal bacterial communities. Several studies have observed that changes in the intestinal microbiota associated with exercise are beneficial for promoting intestinal mucosal integrity and overall metabolic function in the individual. In humans, intestinal bacterial biodiversity has been observed to be higher in athletes compared to sedentary subjects (normalized by body weight, age, and gender). In fact, there is evidence that a chronic exercise routine can restore the intestinal microbiota to a healthy profile in individuals with intestinal dysbiosis. In rats and mice, chronic exercise increases the biodiversity of Firmicutes, Bifidobacteria, and Actinobacteria and reduces the proportion of Bacteroides. Some data show how the presence of intestinal microbiota affects muscle performance, for example, it was found that germ-free mice had greater swimming endurance compared to germ-free mice, and when the latter were colonized with bacteria in the gut, the mice increased their physical endurance and swam for longer. The main objective of this project is to carry out fecal microbiota transplants (FMT) from physically active young donors to a cohort of older individuals to evaluate their effect on muscle, cognitive, and metabolic function. FMT in older adults is planned to be performed by administering lyophilized microbiota capsules. By restoring microbial diversity, it is expected to improve the quality and function of skeletal muscles, leading to greater cognitive and metabolic resilience. It is important to mention that modifications of the intestinal microbiota have been associated with direct and specific effect Покажи пълното описание...

Inclusion Criteria: * Individuals aged 65-84 years * Men and women * Involuntary total body weight variation in the last 6 months \< 10% * Self-sufficiency (with a score \>60 on the Barthel index) * Fasting plasma glucose ≤ 7.2 mmol/l or glycosylated hemoglobin (HbA1c) ≤ 8% in the last 6 months. * Must be able to swallow capsules Exclusion Criteria: * Systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg at selection * Allergy to rifaximin * Acute infection or inflammatory condition in the last 4 weeks * Use of antibiotics in the last 12 weeks * Use of probiotics in the last 12 weeks * Hospitalization in the last 12 weeks * Current or within the last 6 months use of insulin * Difficulty swallowing (dysphagia) * Diagnosis of Inflammatory bowel disease * Diagnosis of Crohn's disease * Diagnosis of Ulcerative colitis * Diagnosis of Clostridium difficile infection * Diagnosis of Colon cancer * Treatment with immunosuppressive therapy for organ transplant * Diagnosis of leukemia * Diagnosis of lymphoma * Diagnosis of mesenchymal diseases except osteoarthritis * Corticosteroid users * Biological therapy users * Individuals with a history of autoimmune or chronic inflammatory conditions (rheumatoid arthritis, chronic or active hepatitis B or C, human immunodeficiency virus, pancreatitis, or liver cirrhosis) * Individuals with an active malignancy, * Current drug or alcohol abuse (more than three drinks per day or more than seven drinks per week). * Diagnosis of dementia (To assess the presence of this disease at the time of enrollment, the following questions will be asked: Have you been diagnosed with dementia? \_\_\_Yes \_\_\_ No Do you take any of these medications? * Donepezil \_\_\_Yes \_\_\_No * Rivastigmine \_\_\_Yes \_\_\_No If the answer is positive to any of these questions, the patient will be excluded from the study. If there are doubts about the cognitive status of the potential participant by the recruiter, a Mini-Mental State Examination (MMSE) will be conducted, and the score must be ≥ 20)