The gut microbiome and its interaction with aging is a topic of increasing interest in the scientific community. The microbial populations shift for reasons that remain unclear, becoming less helpful and more inflammatory. There is a two-way relationship between the microbiome and the immune system. Inflammatory microbes aggravate the immune system, contributing to the chronic inflammation of aging, but additionally the immune system is responsible for gardening the gut microbiome, removing problematic microbes. As the immune system fails with age, potentially harmful microbial populations can grow in size to cause greater issues.

Calorie restriction is known to improve health, slow aging, and alter the gut microbiome. It is thought that the majority of the beneficial effects of calorie restriction are mediated by upregulation of autophagy in tissues throughout the body. But is the gut microbiome also important? Today’s research materials are an example of the way in which researchers are attempting to answer that question, here by taking human microbial populations and putting them into mice, in order to see the differences pre- and post-calorie restriction.

A Low-Calorie Diet Alters the Gut Microbiome and Delays Immune Aging

Obesity increases the risk of developing high blood pressure, heart attack, or type 2 diabetes mellitus and can cause inflammation in the body that weakens the immune system through an accumulation of specific memory T cells and memory B cells. This process is called immune senescence, an age-related change in the immune system. In obese people, the development of metabolic diseases such as type 2 diabetes can be delayed by a low-calorie diet. In addition, such a diet also has a positive effect on the immune system. But exactly how the positive effects are mediated and what role the gut microbiome plays in this process is not yet known.

Researchers first analyzed how a very low-calorie diet (800 kcal/day for 8 weeks) affected the gut microbiome of an obese woman. In the next step, the researchers transplanted the gut microbiota before and after the diet intervention into germ-free mice to establish a gnotobiotic mouse model. By transplanting the diet-altered microbiota, glucose metabolism improved and fat deposition decreased. In addition, mass cytometry showed that the level of specific memory T and B cells was also reduced, indicating delayed immune senescence.

Effects of caloric restriction on the gut microbiome are linked with immune senescence

Caloric restriction can delay the development of metabolic diseases ranging from insulin resistance to type 2 diabetes and is linked to both changes in the composition and metabolic function of the gut microbiota and immunological consequences. However, the interaction between dietary intake, the microbiome, and the immune system remains poorly described.

We transplanted the gut microbiota from an obese female before (AdLib) and after (CalRes) an 8-week very-low-calorie diet (800 kcal/day) into germ-free mice. We used 16S rRNA sequencing to evaluate taxa with differential abundance between the AdLib- and CalRes-microbiota recipients and single-cell multidimensional mass cytometry to define immune signatures in murine colon, liver, and spleen.

Recipients of the CalRes sample exhibited overall higher alpha diversity and restructuring of the gut microbiota with decreased abundance of several microbial taxa (e.g., Clostridium ramosum, Hungatella hathewayi, Alistipi obesi). Transplantation of CalRes-microbiota into mice decreased their body fat accumulation and improved glucose tolerance compared to AdLib-microbiota recipients. Finally, the CalRes-associated microbiota reduced the levels of intestinal effector memory CD8+ T cells, intestinal memory B cells, and hepatic effector memory CD4+ and CD8+ T cells.


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