September 14, 2022
Faculty of Pharmacy, Keio University
A research group led by Keio University and Kyoto University has discovered that differences in dietary protein sources consumed after antibiotic administration alter the pathology of Clostridioides difficile infection (CDI) via the gut microbiota. This research is the result of work by Kyosuke Yakabe, a student in the Doctoral Programs at the Graduate School of Pharmaceutical Sciences, Keio University; Professor Yun-gi Kim of the same university's Faculty of Pharmacy; and a research group centered at Kyoto University.
CDI is an infectious disease that develops when C. difficile proliferates in the intestine and produces toxins, triggered by a disruption of the gut microbiota due to antibiotic administration. It causes symptoms such as diarrhea, lower abdominal pain, fever, and leukocytosis. Fecal microbiota transplantation (FMT), which involves transplanting gut bacteria from a healthy donor to a patient, is highly effective against CDI, indicating that the gut microbiota significantly influences the onset and prevention of CDI. The composition of the gut microbiota and the metabolites they produce fluctuate depending on the food we consume daily. Therefore, we hypothesized that differences in dietary components could alter the pathology of CDI through the gut microbiota.
In this study, we found that the source of protein in the diet affects the pathology of CDI. Specifically, we found that consuming soy protein as a protein source, compared to casein, promoted the growth of C. difficile in the intestine and worsened the pathology of CDI. We also discovered that soy protein increases bacteria of the genus Lactobacillus in the gut, and the amino acids released in this process promote the growth of C. difficile . Furthermore, it was revealed that an enzyme that digests proteins extracellularly (PrtP) is involved in amino acid production by Lactobacillus bacteria. In fact, in Lactobacillus bacteria lacking the PrtP gene, the ability to produce amino acids was reduced, and the growth-promoting effect on C. difficile was also attenuated.
CDI accounts for 20-30% of antibiotic-associated diarrhea and is the most common infectious diarrhea among hospitalized patients. Previously reported risk factors for CDI, besides antibiotics, include advanced age, length of hospital stay, proton pump inhibitors (which suppress gastric acid), and underlying diseases. This study has revealed that dietary components, particularly the type of protein consumed, significantly affect the onset and severity of CDI after antibiotic administration. In the future, we expect the establishment of safer and simpler diet-focused prevention methods for CDI and the development of new prophylactic drugs that lower amino acid concentrations in the intestine.
This research was published in the online edition of the international scientific journal "Cell Reports" on September 13, 2022 (U.S. Eastern Standard Time).
For the full press release, please see below.