{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T10:37:11Z","timestamp":1762079831385,"version":"3.41.2"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T00:00:00Z","timestamp":1642118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p><jats:italic>Cryptosporidium parvum<\/jats:italic> infection is very common in infants, immunocompromised patients, or in young ruminants, and chitosan supplementation exhibits beneficial effects against the infection caused by <jats:italic>C. parvum<\/jats:italic>. This study investigated whether chitosan supplementation modulates the gut microbiota and mediates the TLR4\/STAT1 signaling pathways and related cytokines to attenuate <jats:italic>C. parvum<\/jats:italic> 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 \u00d7 10<jats:sup>6<\/jats:sup> C<jats:italic>. parvum<\/jats:italic> 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 (<jats:italic>p &amp;lt;<\/jats:italic> 0.01) reduced <jats:italic>C. parvum<\/jats:italic> oocyst excretion in infected mice treated with chitosan compared with the infected mice that received no treatment. Chitosan-fed infected mice showed significantly (<jats:italic>p &amp;lt;<\/jats:italic> 0.01) decreased mRNA expression levels of interferon-gamma (IFN-\u03b3) and tumor necrosis factor-\u03b1 (TNF-\u03b1) compared to infected mice that received no treatment. Chitosan significantly inhibited TLR4 and upregulated STAT1 protein expression (<jats:italic>p &amp;lt;<\/jats:italic> 0.01) in <jats:italic>C. parvum<\/jats:italic>-infected mice. 16S rRNA sequencing analysis revealed that chitosan supplementation increased the relative abundance of Bacteroidetes\/<jats:italic>Bacteroides<\/jats:italic>, while that of Proteobacteria, Tenericutes, Defferribacteres, and Firmicutes decreased (<jats:italic>p &amp;lt;<\/jats:italic> 0.05). Overall, the findings revealed that chitosan supplementation can ameliorate <jats:italic>C. parvum<\/jats:italic> infection by remodeling the composition of the gut microbiota of mice, leading to mediated STAT1\/TLR4 up- and downregulation and decreased production of IFN-\u03b3 and TNF-\u03b1, and these changes resulted in better resolution and control of <jats:italic>C. parvum<\/jats:italic> infection.<\/jats:p>","DOI":"10.3389\/fimmu.2021.784683","type":"journal-article","created":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T05:00:55Z","timestamp":1642136455000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Chitosan Protects Immunosuppressed Mice Against Cryptosporidium parvum Infection Through TLR4\/STAT1 Signaling Pathways and Gut Microbiota Modulation"],"prefix":"10.3389","volume":"12","author":[{"given":"Sajid 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