Intestinal bacteria in type 2 diabetes: being overweight is pivotal

Those who are overweight also have a significantly increased risk of developing type 2 diabetes. In fact, 86% of all patients with this type of diabetes are overweight or obese. In both of these metabolic diseases, genetic predisposition, lifestyle e.g. diet and exercise, but also the composition of the intestinal bacteria, all play a role.

Because the bacteria in the gut, the so-called intestinal microbiome, help humans digest food and therefore have a direct influence on the metabolism.

In people with obesity, the diversity of the intestinal bacteria is greatly reduced compared to normal people. In particular, “good” intestinal bacteria, which fulfil functions for a healthy metabolism, are reduced. The same applies to overweight people with type 2 diabetes.

Scientists from the Institute of Clinical Molecular Biology (IKMB) at Kiel University’s (CAU) Faculty of Medicine are researching the interrelationships between genetics, nutrition and the microbiome.

An IKMB research team, together with international colleagues, has now published work in the renowned scientific journal Cell Host & Microbe proving changes in the microbiome related to obesity, and only minimal differences specific to type 2 diabetes.

“Since type 2 diabetes usually occurs together with being overweight, it is difficult to distinguish which changes in the intestinal bacteria are specifically only from type 2 diabetes, and which are from obesity,” explained Professor Andre Franke, Director at the IKMB and board member of the Cluster of Excellence “Precision Medicine in Chronic Inflammation” (PMI), regarding the initial situation. In close collaboration with Professor Curtis Huttenhower from the Harvard T.H. Chan School of Public Health in Boston, the team led by Franke therefore specifically tackled this issue.

Intestinal microbiome changes with obesity and use of medication

To do so, they examined the intestinal microbiome of 1,280 stool samples. These came from so-called cohort studies, in which biological samples such as urine and blood, as well as information about lifestyle, diseases and use of medication, were regularly collected from numerous subjects over lengthy time periods. For the current research, the team led by Franke specifically selected subjects from three groups: people of normal weight, overweight people and overweight people with type 2 diabetes.

The investigations showed that the microbiome is changed significantly in overweight individuals – both with and without type 2 diabetes – compared to those of normal weight. The difference between obese people with and without type 2 diabetes was relatively low. “The significant reduction previously observed in the biodiversity of the intestinal bacteria in these people thus especially relates to obesity, and less to type 2 diabetes,” explained the Danish lead author of the publication, Louise Thingholm from the IKMB in Kiel.

In addition, the team used the cohorts to help examine the impact of regularly taking medication and nutritional supplements on the intestinal microbiome. Their finding: not only medications which lower blood pressure, painkillers, antidepressants and antidiabetic agents, but also food supplements such as magnesium, vitamins, calcium and especially iron, all alter the intestinal microbiome noticeably. “Such substances, which many people hope will provide a health-boosting effect, change our intestinal bacteria. In this way, they also affect how we digest our food, and could possibly also play a role in metabolic diseases,” said Franke.

Specific intestinal bacteria occur more frequently with type 2 diabetes

Thus, both obesity as well as potential use of medication affect the intestinal bacteria of patients with type 2 diabetes. Using bioinformatic methods, the research team adjusted for this influence on the microbiome changes in people with type 2 diabetes. This allowed them to search for individual species of bacteria, which specifically occur more frequently in type 2 diabetics.

“If we understand more clearly what these changes in the microbiome specifically cause, and which the key bacteria here are, then we can attack them in a targeted manner in the future, and therefore influence the related illness – or perhaps also its pathogenesis,” explained Franke. “We are currently trying to obtain further funding, so that we can specifically look for therapeutic approaches to metabolic diseases in the microbiome, in an independent research project. The microbiome is especially interesting because we can influence it much more easily than our own genetic material, for example.”

Photos are available to download:

https://precisionmedicine.de/pm/material/20190819_Stuhlproben1.jpg
The DNA of the intestinal bacteria is extracted from stool samples. Based on the DNA, the scientists from the Institute of Clinical Molecular Biology (IKMB) at Kiel University (CAU) analyze the composition of the intestinal microbiome.
Photo/Copyright: C. Bang / Kiel University

https://precisionmedicine.de/pm/material/20190819_Stuhlproben2.jpg
An employee at the Institute of Clinical Molecular Biology (IKMB) at Kiel University (CAU) prepares the stool samples. The DNA of the intestinal bacteria is extracted from these samples in order to determine the composition of the intestinal microbiome.
Photo/Copyright: C. Bang / Kiel University.

https://precisionmedicine.de/pm/material/20190819_Sequenzierung.jpg
The DNA of the intestinal bacteria is analyzed using modern sequencing devices.
Photo/Copyright: C. Urban / Kiel University.

https://precisionmedicine.de/pm/material/20190819_Franke.jpg
Professor Andre Franke, Director of the Institute of Clinical Molecular Biology (IKMB) and board member of the Cluster of Excellence “Precision Medicine in Chronic Inflammation” (PMI).
Photo/Copyright: K. Nees / Kiel University.

Press contact:
Frederike Buhse
Tel.: +49 (0)431 880 4682 e-mail: fbuhse@uv.uni-kiel.de
Internet: https://precisionmedicine.de

The Cluster of Excellence “Precision Medicine in Chronic Inflammation” (PMI) is being funded from 2019 to 2025 through the German Excellence Strategy (ExStra). It succeeds the “Inflammation at Interfaces” Cluster, which was already funded in two periods of the Excellence Initiative (2007-2018). Around 300 members from eight institutions at four locations are involved: Kiel (Kiel University, University Medical Center Schleswig-Holstein (UKSH), Muthesius University of Fine Arts and Design, Kiel Institute for the World Economy (IfW), Leibniz Institute for Science and Mathematics Education (IPN)), Lübeck (University of Lübeck, University Medical Center Schleswig-Holstein (UKSH)), Plön (Max Planck Institute for Evolutionary Biology) and Borstel (Research Center Borstel – Leibniz Lung Center).

The goal is to translate interdisciplinary research findings on chronic inflammatory diseases of barrier organs to healthcare more intensively, as well as to fulfil previously unsatisfied needs of the patients. Three points are important in the context of successful treatment, and are therefore at the heart of PMI research: the early detection of chronic inflammatory diseases, the prediction of disease progression and complications, and the prediction of individual responses to treatment.

Cluster of Excellence “Precision Medicine in Chronic Inflammation”
Scientific Office, Head: Dr habil. Susanne Holstein
Postal address: Christian-Albrechts-Platz 4, 24118 Kiel, Germany
Contact: Sonja Petermann
Tel.: +49 431 880-4850, Fax: +49 (0)431 880-4894
E-mail: spetermann@uv.uni-kiel.de
Twitter: PMI @medinflame

Prof. Andre Franke
Institute of Clinical Molecular Biology (IKMB), Kiel University
Tel.: +49 (0)431 500 15110
E-mail: a.franke@mucosa.de

Thingholm et al., Obese Individuals with and without Type 2 Diabetes Show Different Gut Microbial Functional Capacity and Composition, Cell Host & Microbe (2019), https://doi.org/10.1016/j.chom.2019.07.004