AUTHOR=Jo Sung-Hyun , Jeon Hyo-Jin , Song Won-Suk , Lee Jae-Seung , Kwon Ji-Eun , Park Ji-Hyeon , Kim Ye-Rim , Kim Min-Gyu , Baek Ji-Hyun , Kwon Seo-Young , Kim Jae-Seok , Yang Yung-Hun , Kim Yun-Gon 

TITLE=Unveiling the inhibition mechanism of Clostridioides difficile by Bifidobacterium longum via multiomics approach

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1293149

DOI=10.3389/fmicb.2023.1293149

ISSN=1664-302X

ABSTRACT=<p>Antibiotic-induced gut microbiota disruption constitutes a major risk factor for <italic>Clostridioides difficile</italic> infection (CDI). Further, antibiotic therapy, which is the standard treatment option for CDI, exacerbates gut microbiota imbalance, thereby causing high recurrent CDI incidence. Consequently, probiotic-based CDI treatment has emerged as a long-term management and preventive option. However, the mechanisms underlying the therapeutic effects of probiotics for CDI remain uninvestigated, thereby creating a knowledge gap that needs to be addressed. To fill this gap, we used a multiomics approach to holistically investigate the mechanisms underlying the therapeutic effects of probiotics for CDI at a molecular level. We first screened <italic>Bifidobacterium longum</italic> owing to its inhibitory effect on <italic>C. difficile</italic> growth, then observed the physiological changes associated with the inhibition of <italic>C. difficile</italic> growth and toxin production <italic>via</italic> a multiomics approach. Regarding the mechanism underlying <italic>C. difficile</italic> growth inhibition, we detected a decrease in intracellular adenosine triphosphate (ATP) synthesis due to <italic>B. longum</italic>–produced lactate and a subsequent decrease in (deoxy)ribonucleoside triphosphate synthesis. <italic>Via</italic> the differential regulation of proteins involved in translation and protein quality control, we identified <italic>B. longum</italic>–induced proteinaceous stress. Finally, we found that <italic>B. longum</italic> suppressed the toxin production of <italic>C. difficile</italic> by replenishing proline consumed by it. Overall, the findings of the present study expand our understanding of the mechanisms by which probiotics inhibit <italic>C. difficile</italic> growth and contribute to the development of live biotherapeutic products based on molecular mechanisms for treating CDI.</p>