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

Around 2 billion people worldwide are overweight. 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 and 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. In a recent study, researchers have now investigated the interactions between calorie-reduced diets, the microbiome, metabolism and the immune system.

Calorie-reduced diet alters the gut microbiome

For this purpose, they 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. "In this way, we were able to determine the sole effects of the diet-shaped gut microbiome on metabolism and the immune system," said Reiner Jumpertz-von Schwartzenberg, last author of the study and a scientist at the Institute of Diabetes Research and Metabolic Diseases of Helmholtz Munich at the University of Tübingen, a partner of the German Center for Diabetes Research (DZD). He led the study together with Hans-Dieter Volk and Joachim Spranger of Charité. Dr. Reiner Junpertz-von Schwartzenberg is Junior Research Group Leader at the Cluster of Excellence "Controlling Microbes to Fight Infections" (CMFI).

Diet-altered gut microbiome improves metabolism and delays immune senescence

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. "This indicates delayed immune senescence," said Julia Sbierski-Kind, first author of the study.

"These findings suggest that the positive effects of a low-calorie diet on metabolism and the immune system are mediated via the gut microbiome," Sbierski-Kind said. However, the authors of the study emphasize that the investigation has so far only been conducted with the microbiome of one person and that the experiments will have to be repeated with additional subjects to confirm the results. The new findings could also be interesting for medical practice in the long term. "An improved understanding of the complex interplay between diet, the microbiome and the immune system may set the stage for the development of new microbiome-based therapeutic avenues to treat metabolic and immune diseases," said Jumpertz-von Schwartzenberg.

About the study: 

The aim of the study was to determine the interactions between a calorie-restricted diet, microbiome and the immune system. To this end, a human dietary intervention trial was combined with gnotobiotic experiments in which immunophenotyping was determined by multidimensional single cell mass cytometry. The following institutes and research facilities were involved:

• German Center for Diabetes Research (DZD)
• Institute of Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Munich at the University of Tübingen
• Department of Internal Medicine IV, Tübingen University Hospital
• Cluster of Excellence EXC 2124 "Controlling Microbes to Fight Infections" (CMFI), University of Tübingen
• Institute of Medical Immunology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt University of Berlin
• Department of Endocrinology and Metabolism, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt University of Berlin
• Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Flow & Mass Cytometry Core Facility, Berlin

(Source: Press Release DZD, Nieser)

Sbierski-Kind J, Grenkowitz S, Schlickeiser S, Sandforth A, Friedrich M, Kunkel D, Glauben R, Brachs S, Mai K, Thürmer A, Radonić A, Drechsel O, Turnbaugh PJ, Bisanz JE, Volk HD, Spranger J, von Schwartzenberg RJ. Effects of caloric restriction on the gut microbiome are linked with immune senescence. Microbiome 10(1):57. (2022) doi: 10.1186/s40168-022-01249-4.

Dr. Reiner Jumpertz-von Schwartzenberg has been a senior physician at the Medical Clinic IV Endocrinology, Diabetology and Nephrology at Tübingen University Hospital (research focus: translational obesity research) and junior research group leader of the Cluster of Excellence "Controlling Microbes to Fight Infections" since 2021. He is a scientist at the DZD partner Institute for Diabetes Research and Metabolic Diseases of Helmholtz Munich at the University of Tübingen. Previously, he worked as a physician and clinical scientist at Charité.

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