A low-calorie diet can delay the development of diabetes and boost the immune system

Gut with Firmicutes and Bacteroidetes bacteria. Credit: © IMFC/Leon Kokkoliadis

A low-calorie diet alters the gut microbiome and delays immune aging

A low-calorie diet not only delays the development of metabolic diseases, but also has a positive effect on the immune system. Researchers have now shown for the first time that this effect is caused by an altered gut microbiome, which slows the deterioration of the immune system in older people (immune senescence). The research study was published in the journal Microbiota.

Gut microbiome

The gut microbiome is the term used to describe the totality of all gut microorganisms and bacteria in our digestive tract. Among other things, it influences the immune system and the metabolism of its host.

About 2 billion people in the world are overweight. Obesity increases the risk of developing high blood pressure, heart attack, or type 2 diabetes mellitus. It can also cause inflammation in the body that weakens the immune system through a buildup of specific memory T and B cells. This process is called immune senescence, an age-related change in the immune system.

In obese people, a low-calorie diet can delay the development of metabolic diseases such as type 2 diabetes. In addition, such a diet is beneficial for the immune system. However, it is unclear exactly how the positive effects are brought about and what function the gut microbiota plays in this process. Researchers have now explored the relationships between low-calorie diets, the microbiome, metabolism and the immune system in a new study.

A low-calorie diet alters the gut microbiota

To do this, they first analyzed how a very low-calorie diet (800 kcal/day for 8 weeks) affected the intestinal microbiome of an obese woman. In the next step, the researchers transplanted the gut microbiota before and after the dietary intervention into germ-free mice to establish a gnotobiotic mouse model. “In this way, we were able to determine the unique effects of the gut microbiome in the form of diet on metabolism and the immune system,” said Reiner Jumpertz-von Schwartzenberg, the study’s final author and scientist at the Institute of Diabetes Research and Metabolic Diseases from Helmholtz Munich to the University of Tübingen, partner of the German Center for Diabetes Research (DZD). He led the study with Hans-Dieter Volk and Joachim Spranger of Charité.

Diet-altered gut microbiome improves metabolism and delays immune senescence

By transplanting the diet-modified 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 by the gut microbiome,” Sbierski-Kind said. However, the study authors point out that the investigation has so far only been conducted with the microbiome of a single person and that the experiments will need to be repeated with additional subjects to confirm the results. The new findings could also be of interest for long-term medical practice. “A better understanding of the complex interplay between diet, the microbiome and the immune system may pave the way for the development of new microbiome-based therapeutic avenues to treat metabolic and immune diseases,” said Jumpertz-von Schwartzenberg.

Reference: “The effects of caloric restriction on the gut microbiome are linked to immune senescence” by Julia Sbierski-Kind, Sophia Grenkowitz, Stephan Schlickeiser, Arvid Sandforth, Marie Friedrich, Désirée Kunkel, Rainer Glauben, Sebastian Brachs, Knut Mai, Andrea Thürmer, Aleksandar Radonic, Oliver Drechsel, Peter J. Turnbaugh, Jordan E. Bisanz, Hans-Dieter Volk, Joachim Spranger, and Reiner Jumpertz von Schwartzenberg, April 4, 2022, Microbiome.
DOI: 10.1186/s40168-022-01249-4

About the study:

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

  • German Center for Diabetes Research (DZD)
  • Helmholtz Munich Research Institute for Diabetes and Metabolic Diseases (IDM) at the University of Tübingen
  • Department of Internal Medicine IV (Head: Prof. Andreas Birkenfeld), University Hospital Tübingen
  • Center of Excellence EXC 2124 “Controlling Microbes to Fight Infections” (CMFI), University of Tübingen
  • Institute for Medical Immunology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt University Berlin
  • Department of Endocrinology and Metabolism, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt University Berlin
  • Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Flow & Mass Cytometry Core Facility, Berlin
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