Moreno-Huizar, N. | Search bioRxiv

bioRxiv2020

Hemagglutination by B. fragilis is mediated by capsular polysaccharides and is influenced by host ABO blood type.

Bacterial hemagglutination of red blood cells (RBCs) is mediated by interactions between bacterial cell components and RBC envelope glycans that vary across individuals by ABO blood type. ABO glycans are also expressed on intestinal epithelial cells and in most individuals secreted into the intestinal mucosa, indicating that hemagglutination by bacteria may be informative about bacteria-host interactions in the intestine. Bacteroides fragilis, a prominent member of the human gut microbiota, can hemagglutinate RBCs by an unknown mechanism. Using a novel technology for quantifying bacterial hemagglutination, genetic knockout strains of B. fragilis and blocking antiserums, we demonstrate that the capsular polysaccharides of B. fragilis, polysaccharide B (PSB), and PSC are both strong hemagglutinins. Furthermore, the capacity of B. fragilis to hemagglutinate was much stronger in individuals with Type O blood compared to Types A and B, an adaptation that could impact the capacity of B. fragilis to colonize and thrive in the host. Importance StatementThis study found that the human pathobiont, B. fragilis, hemagglutinates human red blood cells using specific capsular polysaccharides (PSB and PSC) which are known to be important for interacting with and influencing host immune responses. Because the factors found on red blood cells are also abundantly expressed on other tissues and in the mucous, the ability to hemagglutinate sheds light on interactions between bacteria and host throughout the body. Intriguingly, the strength of hemagglutination varied based on the ABO blood type of the host, a finding which could have implications for understanding if an individuals blood type may influence interactions with B. fragilis and its potential as a pathogen versus a commensal.

microbiology↗

bioRxiv2019

Dietary fat and fiber impacts intestinal microbiome resilience to antibiotics and Clostridoides difficile infection in mice

Clostridioides difficile infection (CDI), is the leading cause of hospital-acquired diarrhea and emerging evidence has linked dietary components with CDI pathogenesis, suggesting that dietary modulation may be an effective strategy for prevention. Here, we show that mice fed a high-fat/low-fiber "Western type" diet (WD) had dramatically increased mortality in a murine model of antibiotic-induced CDI compared to a low-fat/low-fiber (LF/LF) diet and standard mouse chow controls. We found that the WD had a pro- C. difficile bile acid composition that was driven in part by higher levels of primary bile acids that are produced to digest fat, and a lower level of secondary bile acids that are produced by the gut microbiome. This lack of secondary bile acids was associated with a greater disturbance to the gut microbiome with antibiotics in both the WD and LF/LF diet compared to mouse chow. Mice fed the WD also had the highest level of toxin TcdA just prior to the onset of mortality, but not of TcdB or increased inflammation. These findings indicate that dietary intervention to decrease fat may complement previously proposed dietary intervention strategies to prevent CDI in high-risk individuals. One Sentence SummaryA high-fat/low-fiber Western type diet promoted mortality in a mouse model of antibiotic-induced C. difficile infection compared to a low-fat/low-fiber diet and chow diet, suggesting that lower dietary fat may be an effective strategy for preventing C. difficile pathology.

microbiology↗