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        New link between diet,

        intestinal stem cells and

        disease discovered

             he intestine is essential       biologists at Helmholtz Munich,     found out is of crucial importance
             for maintaining our energy      we then profiled 27,000 intestinal   for developing alternative
        Tbalance and is a master             cells from control diet and high    non-invasive therapies,” says
        at reacting quickly to changes in    fat/high sugar diet-fed mice.       study leader Heiko Lickert, in
        nutrition and nutrient balance. It   Using new machine learning          summarizing the results. To date,
        manages to do this with the help     techniques, we thus found that      there is no pharmacological
        of intestinal cells that among       intestinal stem cells divide and    approach to prevent, stop or
        other things are specialized in the   differentiate significantly faster in   reverse obesity and diabetes.
        absorption of food components        the mice on an unhealthy diet.”     Only bariatric surgery causes
        or the secretion of hormones. In     The researchers hypothesize that    permanent weight loss and
        adult humans, the intestinal cells   this is due to an upregulation of   can even lead to remission
        regenerate every five to seven       the relevant signaling pathways,    of diabetes. However, these
        days. The ability to constantly      which is associated with an         surgeries are invasive, non-
        renew and develop all types of       acceleration of tumor growth in     reversible and costly to the
        intestinal cells from intestinal     many cancers. “This could be an     healthcare system. Novel non-
        stem cells is crucial for the natural   important link: Diet influences   invasive therapies could happen,
        adaptability of the digestive        metabolic signaling, which leads    for example, at the hormonal
        system. However, a long-term diet    to excessive growth of intestinal   level through targeted regulation
        high in sugar and fat disrupts this   stem cells and ultimately to an    of serotonin levels. The research
        adaptation and can contribute to     increased risk of gastrointestinal   group will examine this and
        the development of obesity, type     cancer,” says Böttcher.             other approaches in subsequent
        2 diabetes, and gastrointestinal                                         studies.
        cancer.                              With the help of this high-
                                             resolution technique, the           Story Source:
        The molecular mechanisms             researchers have also been able     Materials provided by
        behind this maladaptation are        to study rare cell types in the     Helmholtz Zentrum München
        part of the research field of        intestine, for example, hormone-    - German Research Center for
        Heiko Lickert and his group          secreting cells. Among their        Environmental Health. Note:
        at Helmholtz Munich and the          findings, they were able to show    Content may be edited for style
        Technical University of Munich.      that an unhealthy diet leads to a   and length.
        The scientists assume that           reduction in serotonin-producing
        intestinal stem cells play a special   cells in the intestine. This can   Journal Reference:
        role in maladaptation. Using a       result in intestinal inertia (typical   1. Alexandra Aliluev, Sophie
        mouse model, the researchers         of diabetes mellitus) or increased   Tritschler, Michael Sterr, Lena
        investigated the effects of a        appetite. Furthermore, the study    Oppenländer, Julia Hinterdobler,
        high-sugar and high-fat diet and     showed that the absorbing cells     Tobias Greisle, Martin Irmler,
        compared it with a control group.    adapt to the high-fat diet, and     Johannes Beckers, Na Sun,
                                             their functionality increases, thus   Axel Walch, Kerstin Stemmer,
        From high-calorie diet               directly promoting weight gain.     Alida Kindt, Jan Krumsiek,
        to increased risk of                                                     Matthias H. Tschöp, Malte D.
        gastrointestinal cancer              Important basic research for        Luecken, Fabian J. Theis, Heiko
                                             non-invasive therapies              Lickert, Anika Böttcher. Diet-
        “The first thing we noticed was                                          induced alteration of intestinal
        that the small intestine increases   These and other findings            stem cell function underlies
        greatly in size on the high-calorie   from the study lead to a new       obesity and prediabetes in mice.
        diet,” says study leader Anika       understanding of disease            Nature Metabolism, 2021; 3 (9):
        Böttcher. “Together with Fabian      mechanisms associated with a        1202 DOI: 10.1038/s42255-021-
        Theis’ team of computational         high-calorie diet. “What we have    00458-9

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