Lactococcus Lactis and Bifidobacterium Longum Attenuate Clostridioides Difficile- or Clostridium Symbiosum-Induced Colitis and Depression/anxiety-Like Behavior in Male Mice.

Clostridioides difficile causes severe colitis, which induces neuroinflammation and psychiatric disorder. In a preliminary study, we isolated Clostridium symbiosum from the stools of patients with ulcerative colitis. Therefore, we first examined whether oral infection with C. difficile or C. symbiosum could induce colitis and depression in male mice. Orally gavaged C. difficile or C. symbiosum caused diarrhea, bodyweight loss, depression/anxiety-like behavior, and tumor necrosis factor (TNF)-α and interleukin (IL)-6 overexpression in the colon and hippocampus in the pseudo-germ-free (PGF) and specific germ-free (SPF) mice. However, healthy volunteer microbiota-derived Lactococcus lactis P22 and/or Bifidobacterium longum P26 suppressed C. difficile or C. symbiosum growth and TNF-α expression in macrophage cells. They alleviated C. difficile- or C. symbiosum-induced bodyweight loss, diarrhea, and neurobehavioral changes in PGF and SPF mice, while reducing pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) levels in the colon and in the hippocampus. These findings suggest that C. difficile or C. symbiosum can cause colitis and depression/anxiety. Oral administration of P22 and/or P26 may alleviate gut bacteria-induced gut inflammation and depression/anxiety through the inhibition of their growth and inflammatory response.