Experimental colonization with Blastocystis ST4 is associated with protective immune responses and modulation of gut microbiome in a DSS-induced colitis mouse model

Abstract

Background Blastocystis is a common gut protistan parasite in humans and animals worldwide, but its interrelationship with the host gut microbiota and mucosal immune responses remains poorly understood. Different murine models of Blastocystis colonization were used to examine the effect of a common Blastocystis subtype (ST4) on host gut microbial community and adaptive immune system. Results Blastocystis ST4-colonized normal healthy mice and Rag1−/− mice asymptomatically and was able to alter the microbial community composition, mainly leading to increases in the proportion of Clostridia vadinBB60 group and Lachnospiraceae NK4A136 group, respectively. Blastocystis ST4 colonization promoted T helper 2 (Th2) response defined by interleukin (IL)-5 and IL-13 cytokine production, and T regulatory (Treg) induction from colonic lamina propria in normal healthy mice. Additionally, we observed that Blastocystis ST4 colonization can maintain the stability of bacterial community composition and induce Th2 and Treg immune responses to promote faster recovery from experimentally induced colitis. Furthermore, fecal microbiota transplantation of Blastocystis ST4-altered gut microbiome to colitis mice reduced the severity of colitis, which was associated with increased production of short-chain fat acids (SCFAs) and anti-inflammatory cytokine IL-10. Conclusions The data confirm our hypothesis that Blastocystis ST4 is a beneficial commensal, and the beneficial effects of Blastocystis ST4 colonization is mediated through modulating of the host gut bacterial composition, SCFAs production, and Th2 and Treg responses in different murine colonization models.

Gut-Kidney Impairment Process of Adenine Combined with Folium sennae-Induced Diarrhea: Association with Interactions between Lactobacillus intestinalis, Bacteroides acidifaciens and Acetic Acid, Inflammation, and Kidney Function

“…As a highly dynamic and individualized complex ecosystem, the gut miocrobiota produces metabolites SCFAs under the influence of multiple factors that produce a wide range of response effects with the numerous tissues and organs of the organism, participating in the regulation of health and disease [ 39 , 40 ]. The disturbed microbiota caused the abnormal production of the SCFAs, as well as the deregulation of the gut homeostasis, such as the over-activation of the intestinal immunity and the low inflammatory response states [ 41 ].…”

The regulatory function of Blastocystis spp. on the immune inflammatory response in the gut microbiome

“…Interestingly, Deng et al. reported in a second work ( Deng et al., 2022 ) that ST4-altered microbiota from Rag1 −/− mice reduces inflammation in experiment-induced colitis through an increase in “beneficial” microbes such as Akkermansia . Bacteria belonging to Akkermansia are associated with gut health, and the expansion of Akkermansia can increase mucus production to ameliorate intestinal inflammation ( Everard et al., 2013 ).…”

Gut Microbiota Shifting in Irritable Bowel Syndrome: The Mysterious Role of Blastocystis sp.

“…Later, an altered gut microbial composition was documented in normal healthy mice and Rag1 −/− mice colonized by Blastocystis sp. ST4, mainly by an increased proportion of Clostridia vadinBB60 group and Lachnospiraceae NK4A136 group, respectively ( 104 ). These results confirmed the protective role of Blastocystis sp.…”

“…These results confirmed the protective role of Blastocystis sp. ST4 in the modulation of the gut microbiota to reduce inflammation ( 104 ). Blastocystis sp.…”