Abstract
Probiotics might offer an attractive alternative to prevent and control Clostridium difficile (C. difficile) infection (CDI). Limited information is available on the ability of commercially used bifidobacterial strains to inhibit C. difficile. This study examined the anti-clostridial effects of Bifidobacterium longum JDM301, a widely used commercial probiotic strain in China, in vitro and in vivo. In vitro evaluation revealed a significant reduction in C. difficile counts when JDM301 was co-cultured with C. difficile, which was correlated with the significant decrease in clostridial toxin titres (TcdA and TcdB). Furthermore, the cell-free culture supernatants (CFS) of JDM301 inhibited C. difficile growth and degraded TcdA and TcdB. Notably, the results showed that acid pH promoted the degradation of TcdA by CFS from JDM301. Furthermore, comparative studies among 10 B. longum strains were performed, which showed that the inhibitory effect of CFS from JDM301 was similar with the other 8 B. longum strains and higher than strain BLY1. However, when it was neutralized, the significant different was lost. When present together, it was suggested that the acid pH induced by probiotics not only played important roles in the growth inhibition against C. difficile resulting in the reduction of toxins titres, but also directly promoted the degradation of clostridial toxin. In vivo studies proved that JDM301 partially relieved damage to tissues caused by C. difficile and also decreased the number of C. difficile and toxin levels. In summary, our results demonstrated that the commercial strain, JDM301 could be considered a probiotic able to exert anti-toxin capability and most of the CFS from Bifidobacterium were able to inhibit the growth of C. difficile, depending on acid pH. These results highlighted a potential that JDM301 could be helpful in preventing CDI and that most of the bifidobacterial strains could (at least partially) exert protective effects by reducing toxin titres through growth inhibition against toxigenic C. difficile.
Highlights
Clostridium difficile (C. difficile) is an obligate anaerobic gram-positive spore-forming bacillus
Our results showed that the CFS from B. longum JDM301 could directly cause the degradation of C. difficile toxin, as both the TcdA and TcdB were undetectable in the C. difficile supernatant treated with original CFS from B. longum JDM301 (Figures 3A–D)
Together with the significant reduction of clostridial number and toxin in C. difficile infection (CDI) mice treated with bifidobacteria, these results suggested that strain B. longum JDM301 exerted antagonistic activity against C. difficile and relieved the damage of enteric tissues caused by this pathogen in vivo
Summary
Clostridium difficile (C. difficile) is an obligate anaerobic gram-positive spore-forming bacillus. Standard treatment by antibiotics for CDI results in disruptive effect on the colonic microbiota (Kociolek and Gerding, 2016). As stated by (Kociolek and Gerding, 2016; Petrosillo, 2018), the standard antibiotic treatment for CDI (metronidazole and vancomycin), was limited by their broad spectrum and further disturbance of the intestinal flora. Probiotics can protect the host against pathogens by restoring the complex balance of the indigenous microbiota in gut, modulation of immune system and inhibition of the growth of pathogen, which can limit the need for additional antibiotic treatment (Parkes et al, 2009; Kumar et al, 2016). Studies related to the role of bifidobacteria in modulating the immune response against CDI are limited, especially for widely used bifidobacterial strain in vivo. Comparative studies among bifidobacterial strains were performed to reveal the difference among the inhibitory effects against C. difficile growth by cell-free culture supernatants (CFS) from these symbiotic bacteria
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