Abstract
Cryptosporidium parvum infection is very common in infants, immunocompromised patients, or in young ruminants, and chitosan supplementation exhibits beneficial effects against the infection caused by C. parvum. This study investigated whether chitosan supplementation modulates the gut microbiota and mediates the TLR4/STAT1 signaling pathways and related cytokines to attenuate C. parvum infection in immunosuppressed mice. Immunosuppressed C57BL/6 mice were divided into five treatment groups. The unchallenged mice received a basal diet (control), and three groups of mice challenged with 1 × 106 C. parvum received a basal diet, a diet supplemented with 50 mg/kg/day paromomycin, and 1 mg/kg/day chitosan, and unchallenged mice treated with 1 mg/kg/day chitosan. Chitosan supplementation regulated serum biochemical indices and significantly (p < 0.01) reduced C. parvum oocyst excretion in infected mice treated with chitosan compared with the infected mice that received no treatment. Chitosan-fed infected mice showed significantly (p < 0.01) decreased mRNA expression levels of interferon-gamma (IFN-γ) and tumor necrosis factor-α (TNF-α) compared to infected mice that received no treatment. Chitosan significantly inhibited TLR4 and upregulated STAT1 protein expression (p < 0.01) in C. parvum-infected mice. 16S rRNA sequencing analysis revealed that chitosan supplementation increased the relative abundance of Bacteroidetes/Bacteroides, while that of Proteobacteria, Tenericutes, Defferribacteres, and Firmicutes decreased (p < 0.05). Overall, the findings revealed that chitosan supplementation can ameliorate C. parvum infection by remodeling the composition of the gut microbiota of mice, leading to mediated STAT1/TLR4 up- and downregulation and decreased production of IFN-γ and TNF-α, and these changes resulted in better resolution and control of C. parvum infection.
Highlights
The mammalian gut consists of substantial bacterial communities of 500–1,000 species with a total number of nearly 100 trillion [1, 2]
Mainly sluggish movement, ruffled fur, lack of movement, and loss of appetite, were observed in mice infected with C. parvum and not receiving any treatment compared to the mice treated with chitosan
Studies have reported both in vivo and in vitro treatment effects of halofuginone lactate, ginsenoside-Rh2, and curcurbitacin-B against Cryptosporidium [32, 33]. These compounds showed adverse effects and failed to eradicate the infection. Some antibiotics such as azithromycin, sulfaquinoxaline, and paromomycin have been shown to reduce the level of infection and stop the shedding of C. parvum oocysts, but there is a risk of antibiotic residues remaining
Summary
The mammalian gut consists of substantial bacterial communities (microbiota) of 500–1,000 species with a total number of nearly 100 trillion [1, 2]. These large microbial communities play an important role in energy production for the host, protection against various pathogens, and shaping of the intestinal epithelium [3, 4]. Recent studies have shown that chitosan nanoparticles (Cs NPs) are an effective agent against fungal, protozoan, and bacterial diseases and are commonly used as transporters for drug delivery [11, 12]. Recent studies have confirmed the antiCryptosporidium efficacy of chitosan and its nanoparticles in CD1 outbred mice and HCT-8 and Caco-2 cell lines [17, 18], but the protective mechanisms remain to be elucidated
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