A recent study published in The Journal of Nutrition, Health & Aging found that the intestinal microbiome plays a critical role in the metabolic processes that affect cognition, body composition, and immune function. Modulating these processes together contributes to healthy aging.
Aging is marked by low-grade chronic systemic inflammation resulting from the accumulating antigenic load through ‘inflammaging’.
Frailty syndrome, a multifactorial condition, is common among the elderly and causes significant functional impairment. The gastrointestinal tract plays a major role in the development of frailty syndrome. The syndrome can be attributed to preexisting diseases, malnutrition, low physical activity, accumulation of cellular damage, uncontrolled inflammation, psychological alterations, sociodemographic factors, and polypharmacy. It may lead to adverse events, even death, when the patient is exposed to stressful conditions.
The gut microbiome affects the geriatric population, especially those suffering from frailty syndrome. Aging modifies the natural barrier of the gastrointestinal tract (GI tract), which permits specific microbes and their metabolites to enter the systemic circulation leading to inflammation.
In addition to food digestion and absorption, the GI tract plays an important role in immune tolerance and serves as a habitat for commensal microbes. The gut microbiome comprises viruses, bacteria, and yeasts, and the proportion of their occurrence could be specific to each individual. In humans, the bacterial phyla Firmicutes and Bacteroides constitute nearly 90% of the gut microbiome.
Aging alters the gut microbiota, leading to many age-related diseases. However, the association of aging and gut microbiome with frailty syndrome remains unclear.
Probiotics are supplements containing live microbes that modulate the gut microbiome by competitively inhibiting certain pathogenic species. These are available in various formulations and have different effect and target sites.
Prebiotics are insoluble carbohydrates that are mainly organic compounds, but they can also be derived synthetically. They provide energy to the intestinal microbiome. Symbiotics contain substrates and live microorganisms that are beneficial to host health. They are of two types – complementary symbiotics targeting autochthonous microorganisms and synergistic symbiotics where substrates are selectively used by microorganisms administered in conjunction. However, the health impacts of symbiotics remain unclear.
This study reviewed the influence of the gut microflora on the health of elderly individuals and enumerated the possible interventions that could modulate the GI tract microbiome, with an emphasis on patients with frailty syndrome.
The gut microbiota is grouped into three enterotypes; Bacteroides (Bacteroidaceae family), Prevotella (Prevotellaceae family), and Ruminococcus (Ruminococcaceae family) are the most found genera among the three enterotypes. The enterotypes constituting the main gut microbiome are approximately similar in various age groups.
However, exercise frequency, diet, diseases, age, antibiotic usage, lactation method, type of birth, body-mass index, intra- and extraintestinal diseases, and the anatomical area influence the gut microbiota composition.
Some of these are individual host-related factors. The gut microbiome is also modulated by epithelial morphology, genetic characteristics of the host, epithelial immune components, use of prebiotics and probiotics, fecal transplantation, and exposure to external compounds.
Moreover, the three main enterotypes of gut microbiota become less abundant with age and alter the host physiology. The gut microbiome produces short-chain fatty acids (SCFAs) – butyrate, acetate, and propionate, through non-digestive monosaccharide fermentation. The SFCAs are absorbed into systemic circulation in certain amounts and produce varying local and systemic effects, specifically affecting the immune system.
Aging impacts intestinal permeability, which further modifies microbe release and metabolites in the systemic circulation, thereby activating the immune system. Aging is influenced by the brain-intestine axis and the intestinal microflora, which in turn, affects the gut microbiome via a bidirectional relationship.
The gut microbiome reacts to stressors that affect the immune responses. One example is the age-related alterations in the hypothalamus-pituitary-adrenal axis (HPA)––evident through the circadian cortisol level modifications.
The HPA-axis alterations are also apparent in the changes in adrenocorticotropin hormone and cortisol responses in fragility syndrome. An altered gut microbiome likely causes the altered HPA-axis activation that triggers systemic inflammation.
Chronic inflammation influences dietary protein availability, thereby implying the possibility of the existence of a gut-muscle axis. Decreased SCFAs in the geriatric population cause insulin resistance, which further leads to fat accumulation in the muscles along with decreased muscle function. Therefore, changes in the gut microbiome lead to sarcopenic obesity.
Furthermore, gut microbiota alteration leads to frailty due to malnutrition and age-related anorexia. SFCAs also alter bone metabolism through various mechanisms. SFCAs may be used to treat neurodegenerative diseases in elderly and frail individuals.
Prebiotics are an effective preventive treatment as they improve the GI tract microbiota, resulting in better nutrient absorption and health maintenance. Probiotics are also an effective treatment modality for Improving the gut microflora and decreasing systemic inflammation. Probiotics can be prescribed to individuals with pre-existing comorbidities under various medications.
Malnutrition poses vascular risks and predisposes to cognitive frailty. Factors that exacerbate vascular risk affect cognitive problems associated with frailty syndrome. Frailty syndrome is characterized by deficiencies of nearly all micronutrients; the risk of development of this syndrome increases in settings of micronutrient deficiencies.
Micronutrient supplementation is easily achievable; thus, this is a modifiable factor in the syndrome. Consumption of antioxidants eliminates free radicals, thereby decreasing oxidative stress that causes a decrease in cognition. It has been found that a low intake of vegetarian protein and a poor diet can heighten the frailty risk among the elderly (70-81 years of age).
Both sarcopenia and malnutrition can be treated with adequate energy and protein supplementation in the diet. Regular exercise and diet modification can prevent frailty syndrome. Other interventional options to reduce the predilection for frailty are muscular strength-building exercises post-protein supplementation, leucine, and vitamin D supplementation, dietary intake of minerals and fibers, and creatinine supplementation. Although these are potential interventions for frailty syndrome, they do not directly target the gut microbiota.
Dietary and lifestyle modifications can aid in the long-term maintenance of healthy gut microbiota, which can contribute to achieving healthy aging. Preventing malnutrition and improving gut-microbiome composition goes a long way in preventing frailty as the aging process sets in. Probiotic and prebiotic supplementation offers a modality in such intervention.
- Sánchez y Sánchez de la Barquera, B., Carrillo, B. E., Garrido, J. F., et al. (2022). Emerging Evidence on the Use of Probiotics and Prebiotics to Improve the Gut Microbiota of Older Adults with Frailty Syndrome: A Narrative Review. The Journal of Nutrition, Health & Aging. https://link.springer.com/article/10.1007/s12603-022-1842-4