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Gut Microbiome-Origin Enzyme Functions Similarly to Host One Targeted in Diabetes Management

Researchers have uncovered a gut microbiome-derived enzyme that functions similarly to a host enzyme that is itself a drug target for diabetes management. As they report in Science, researchers from Peking University and elsewhere developed an enzyme activity-screening platform to identify gut microbe-derived enzymes that affect host physiology, which they applied to a set of stool samples from three healthy human volunteers. The researchers' analysis in particular focused on 110 enzymes involved in different human diseases to find that dipeptidyl peptidase 4 (DPP4) had the highest effect size in their samples. DPP4 degrades active glucagon-like peptide-1 (GLP-1) but in mice, the researchers found that the microbial-derived DPP4 did not affect GLP-1 levels among chow-fed mice. It did, however, have an effect on mice fed high-fat diets and mice with "leaky guts." Further, sitagliptin, a DPP4 inhibitor used clinically to treat type 2 diabetes, did not affect microbial-derived DPP4, but through high-throughput screening, they found the daurisoline derivate Dau-d4 could inhibit microbial DPP4 and improve blood glucose homeostasis in mice. The researchers note that these variations in microbial DPP4 activity could be reflected in the differing responses patients treated with sitagliptin exhibit. "Our findings highlight the promise of developing therapies that target both host and gut microbial enzymes to achieve greater clinical efficacy," the researchers write in their paper.

The Scan

Positive Framing of Genetic Studies Can Spark Mistrust Among Underrepresented Groups

Researchers in Human Genetics and Genomics Advances report that how researchers describe genomic studies may alienate potential participants.

Small Study of Gene Editing to Treat Sickle Cell Disease

In a Novartis-sponsored study in the New England Journal of Medicine, researchers found that a CRISPR-Cas9-based treatment targeting promoters of genes encoding fetal hemoglobin could reduce disease symptoms.

Gut Microbiome Changes Appear in Infants Before They Develop Eczema, Study Finds

Researchers report in mSystems that infants experienced an enrichment in Clostridium sensu stricto 1 and Finegoldia and a depletion of Bacteroides before developing eczema.

Acute Myeloid Leukemia Treatment Specificity Enhanced With Stem Cell Editing

A study in Nature suggests epitope editing in donor stem cells prior to bone marrow transplants can stave off toxicity when targeting acute myeloid leukemia with immunotherapy.