Curcumin mitigates Cryptosporidium parvum infection through modulation of gut microbiota and innate immune-related genes in immunosuppressed neonatal mice

• Published in: Microbial pathogenesis Vol. 164; p. 105424
• Main Authors: Rahman, Sajid Ur, Zhou, Keke, Zhou, ShaSha, Sun, Tiancong, Mi, Rongsheng, Huang, Yan, Han, Xiangan, Gong, Haiyan, Chen, Zhaoguo
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.2022
• Subjects: 16S rRNA sequencing; Animals; Animals, Newborn; Cryptosporidiosis - drug therapy; Cryptosporidiosis - prevention & control; Cryptosporidium; Cryptosporidium parvum; Cryptosporidium parvum - physiology; Curcumin; Curcumin - pharmacology; Curcumin - therapeutic use; Feces; Gastrointestinal Microbiome; Gut microbiota; Immunity, Innate; Innate immune responses; Mice; RNA, Ribosomal, 16S - genetics; Gut microbiota; Curcumin; Innate immune responses; Cryptosporidium parvum; 16S rRNA sequencing
• ISSN: 0882-4010; 1096-1208
• DOI: 10.1016/j.micpath.2022.105424

Cryptosporidium parvum is a major cause of diarrheal disease in immature or weakened immune systems, mainly in infants and young children in resource-poor settings. Despite its high prevalence, fully effective and safe drugs for the treatment of C. parvum infections remain scarce, and there is no vaccine. Meanwhile, curcumin has shown protective effects against C. parvum infections. However, the mechanisms of action and relationship to the gut microbiota and innate immune responses are unclear. Immunosuppressed neonatal mice were infected with oocysts of C. parvum and either untreated or treated with a normal diet, curcumin or paromomycin. We found that curcumin stopped C. parvum oocysts shedding in the feces of infected immunosuppressed neonatal mice, prevented epithelial damage, and villi degeneration, as well as prevented recurrence of infection. Curcumin supplementation increased the relative abundance of Bacteroidetes and decreased the relative abundance of Firmicutes and Proteobacteria in mice infected with C. parvum as shown by 16S rRNA gene sequencing analysis. The relative abundance of Lactobacillus, Bacteroides, Akkermansia, Desulfovibrio, Prevotella, and Helicobacter was significantly associated with C. parvum infection inhibited by curcumin. Curcumin significantly (P < 0.01) suppressed IFN-γ and IL -18 gene expression levels in immunosuppressed neonatal C. parvum-infected mice. We demonstrate that the therapeutic effects curcumin are associated with alterations in the gut microbiota and innate immune-related genes, which may be linked to the anti-Cryptosporidium mechanisms of curcumin. [Display omitted] •Curcumin stopped C. parvum oocysts shedding and recurrence of the Cryptosporidium infection.•Curcumin therapeutic effects are linked to alterations in the gut microbiota and innate immune-related genes.•Mature immune system plays a significant role in decreasing susceptibility to C. parvum infection.•Curcumin restore normal gut microbiota composition in immunosuppressed C. parvum infected neonatal mice.