Selection of a novel strain of Christensenella minuta as a future biotherapy for Crohn’s disease

Abstract

Microbiome-based therapies for inflammatory bowel diseases offer a novel and promising therapeutic approach. The human commensal bacteria of the species Christensenella minuta (C. minuta) have been reported consistently missing in patients affected by Crohn’s disease (CD) and have been documented to induce anti-inflammatory effects in human epithelial cells, supporting their potential as a novel biotherapy. This work aimed at selecting the most promising strain of C. minuta for future development as a clinical candidate for CD therapy. Here, we describe a complete screening process combining in vitro and in vivo assays to conduct a rational selection of a live strain of C. minuta with strong immunomodulatory properties. Starting from a collection of 32 strains, a panel of in vitro screening assays was used to narrow it down to five preclinical candidates that were further screened in vivo in an acute TNBS-induced rat colitis model. The most promising candidate was validated in vivo in two mouse models of colitis. The validated clinical candidate strain, C. minuta DSM 33715, was then fully characterized. Hence, applying a rationally designed screening algorithm, a novel strain of C. minuta was successfully identified as the most promising clinical candidate for CD.

Polysaccharides from the seeds of Gleditsia sinensis Lam. attenuate DSS-induced colitis in mice via improving gut barrier homeostasis and alleviating gut microbiota dybiosis

“…Thus, Christensenella plays a major role in gut health. [52][53][54] As expected, the relative abundance of Akkermansia, Lactobacillus, and Christensenella was significantly higher in the ZJMPL and ZJMPH groups than in the DSS group.…”

Sea bass (Lateolabrax maculatus) exerts anti‐ulcerative colitis effects through gut microbiota modulation

“…(Kropp et al, 2021). Recently, a specific C. minuta strain (DSM 22607) was also discovered as the most promising clinical candidate for CD (Relizani et al, 2022). Taken together, sea bass could significantly ameliorate UC through modulating the growth of C. minuta to recover gut barrier dysbiosis (Figure 6).…”

“…It is worth noting that C. minuta could exert excellent anti‐inflammatory properties, which are shown in the prevention of intestinal injury, the inhibition of intestinal inflammation, and mucosal healing in both DSS and TNBS‐induced UC animal model (Kropp et al., 2021). Recently, a specific C. minuta strain (DSM 22607) was also discovered as the most promising clinical candidate for CD (Relizani et al., 2022). Taken together, sea bass could significantly ameliorate UC through modulating the growth of C. minuta to recover gut barrier dysbiosis (Figure 6).…”

A flexible high-throughput cultivation protocol to assess the response of individuals’ gut microbiota to diet-, drug-, and host-related factors

“…It enables rapid and reproducible characterization of diet-, host-, or drug-specific effects, microbe–microbe interactions [ 93 ], strain-specific [ 28 , 31 ], and donor-specific [ 27 ] responses and activities. The protocol can also be applied to cost-efficient screening of drug metabolism by the gut microbiota [ 75 , 76 ], preselection of treatments or dosage prior to costly animal or human trials [ 94 ], development of personalized microbiota-targeted nutritional interventions [ 95 ], identification of responders and non-responders to drugs and prebiotics [ 27 ], and for discovery and investigation of novel live biotherapeutics [ 96 ].…”