Age-related changes in gut microbe populations provide an important contribution to the chronic inflammation that is characteristic of old age. Beneficial species diminish in number, reducing the production of metabolites that aid in optimal cell and tissue function. Harmful species increase in number, interacting with tissue and the immune system in ways that promote chronic inflammation. Practical approaches to reverse the age-related changes observed in the gut microbiome could be realized quite soon, given the will and funding: some form of fecal microbiota transplant, or intense probiotic treatment, perhaps. The former has been demonstrated to work in animals, improving health and extending life, and is already practiced for human patients in the medical community in order to treat certain conditions in which pathological bacteria have contaminated the gut.
Numerous studies have suggested that the composition of the gut microbiota differs between obese and normal weight individuals. However, the cause-effect relationship between obesity and gut microbiota composition is not yet fully understood. This study investigated the short-term responses of the gut microbiota composition to diets with different fat contents. Experimental animals were fed either a a normal diet (ND) or a high-fat diet (HFD) for 20 weeks and the microbial composition was evaluated at 10 and 20 weeks. In agreement with previous studies, body weight and the expression of colonic cytokines increased with higher dietary fat content. The diversity of the gut microbiota was significantly influenced by both age and diet, and two variable showed significant interactions.
At the phylum level, the proportion of Actinobacteria was significantly associated with dietary fat content, while the proportions of Firmicutes and Bacteroidetes were strongly associated with age. In the present study, a HFD significantly elevated the proportions of the phylum Actinobacteria and the class Actinobacteria_c in a positive association with body weight, which have also been shown to be increased in obese subjects and patients with type 2 diabetes.
A growing body of evidence suggests that a HFD increases gut permeability and endotoxemia, resulting in low-grade inflammation and impairment of the gut barrier. Given that bacteria in the phylum Actinobacteria are known as mucin-degrading bacteria, abundant Actinobacteria might be associated with gut barrier impairment induced by a HFD. Indeed, we observed that Actinobacteria was inversely related with tight junction proteins such as E-cadherin and positively associated with proinflammatory cytokines. Therefore, the HFD-mediated increase in Actinobacteria and Actinobacteria_c may play a role in the HFD-induced impairment of the intestinal barrier, leading to colonic inflammation.
We also found that in the phylum Actinobacteria, the class Coriobacteriia and the family Coriobacteriaceae were positively correlated with body weight and proinflammatory cytokines, while the change in the proportions of these bacteria was significantly associated with age. Although the mechanistic effects of age on the Coriobacteriaceae are unknown, it is positively associated with both ROS and inflammatory cytokines, which contribute to metabolic dysfunction.