The Combination of Phages and Faecal Microbiota Transplantation Can Effectively Treat Mouse Colitis Caused by Salmonella enterica Serovar Typhimurium

Abstract

Salmonella enterica serovar Typhimurium (S. Typhimurium) is one of the common causes of human colitis. In the present study, two lytic phages vB_SenS-EnJE1 and vB_SenS-EnJE6 were isolated and the therapeutic effect of the combination of phages and faecal microbiota transplantation (FMT) on S. Typhimurium-induced mouse colitis was investigated. The characteristics and genome analysis indicated that they are suitable phages for phage therapy. Results showed that vB_SenS-EnJE1 lysis 41/54 Salmonella strains of serotype O4, and vB_SenS-EnJE6 lysis 46/54 Salmonella strains of serotypes O4 and O9. Severe inflammatory symptoms and disruption of the intestinal barrier were observed in S. Typhimurium -induced colitis. Interestingly, compared with a single phage cocktail (Pc) or single FMT, the combination of Pc and FMT (PcFMT) completely removed S. Typhimurium after 72 h of treatment, and significantly improved pathological damage and restored the intestinal barrier. Furthermore, PcFMT effectively restored the intestinal microbial diversity, especially for Firmicutes/Bacteroidetes [predominantly bacterial phyla responsible for the production of short-chain fatty acids (SCFA)]. Additionally, we found that PcFMT treatment significantly increased the levels of SCFA. All these data indicated that the combination of phages and FMT possesses excellent therapeutic effects on S. Typhimurium -induced intestinal microbiota disorder diseases. Pc and FMT played roles in “eliminating pathogens” and “strengthening vital qi,” respectively. This study provides a new idea for the treatment of intestinal microbiota disorder diseases caused by specific bacterial infections.

Intestinal colonization with multidrug-resistant Enterobacterales: screening, epidemiology, clinical impact, and strategies to decolonize carriers

“…On this regard, Wang et al recently investigated the therapeutic effect of the combined administration of phage-cocktail and FTM to treat Salmonella enterica Typhimurium-induced mouse colitis, compared to phage treatment and to FMT alone [ 225 ]. The cocktail was composed of 2 phages lytic for serotypes O4 and O9 isolated from sewage and yak feces from Tibet and belonging to the Siphoviridae family.…”

“…Bacterial counts in the colon remained high, as did inflammatory damage, and no significant recovery of the intestinal microbiota was observed. These initial results, together with the outcome of the combined therapy, suggest that both roles—(i) elimination of the pathogen by the phages and (ii) support in restoring the intestinal barrier and microbiota composition by FMT—are necessary for a successful therapy [ 225 ].…”

“…The in vivo mouse model has so far represented the gold-standard to study several aspects linked to the intestinal colonization due to Ent pathogens (e.g., [218,225,226,249]). Nevertheless, though this approach exhibits several advantages-such as the gastrointestinal similarities to humans-many strong limitations can be found in terms of cost, societal, ethical, and logistical issues, which can all together generate very long and laborious investigation periods [265].…”

Reduction of product composition variability using pooled microbiome ecosystem therapy and consequence in two infectious murine models

“…Here, we evidenced for the first time the capability of a pooled microbiotherapy product to prevent the appearance of symptoms induced by SET infection, while some corresponding single donor-derived products failed to be effective. Interestingly, previous work performed by Wang and colleagues ( 62 ) also failed to demonstrate the efficacy of a single donor-derived mice product, although this discrepancy might be related to a different experimental design aiming at curing the infection. Surprisingly, the improved DAI score obtained after pooled fecal microbiotherapy was not associated with a significant decrease in fecal S. Typhimurium load.…”

“…Surprisingly, the improved DAI score obtained after pooled fecal microbiotherapy was not associated with a significant decrease in fecal S. Typhimurium load. This could be explained by the short duration of the experiment and SET’s ability to long-term colonize the digestive tract ( 62 ).…”