Browsing by Author "Wang, Arthur"

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    Cooperation between host immunity and the gut bacteria is essential for helminth-evoked suppression of colitis
    (2021-09-13) Shute, Adam; Callejas, Blanca E.; Li, ShuHua; Wang, Arthur; Jayme, Timothy S.; Ohland, Christina; Lewis, Ian A.; Layden, Brian T.; Buret, André G.; McKay, Derek M.
    Abstract Background Studies on the inhibition of inflammation by infection with helminth parasites have, until recently, overlooked a key determinant of health: the gut microbiota. Infection with helminths evokes changes in the composition of their host’s microbiota: one outcome of which is an altered metabolome (e.g., levels of short-chain fatty acids (SCFAs)) in the gut lumen. The functional implications of helminth-evoked changes in the enteric microbiome (composition and metabolites) are poorly understood and are explored with respect to controlling enteric inflammation. Methods Antibiotic-treated wild-type, germ-free (GF) and free fatty-acid receptor-2 (ffar2) deficient mice were infected with the tapeworm Hymenolepis diminuta, then challenged with DNBS-colitis and disease severity and gut expression of the il-10 receptor-α and SCFA receptors/transporters assessed 3 days later. Gut bacteria composition was assessed by 16 s rRNA sequencing and SCFAs were measured. Other studies assessed the ability of feces or a bacteria-free fecal filtrate from H. diminuta-infected mice to inhibit colitis. Results Protection against disease by infection with H. diminuta was abrogated by antibiotic treatment and was not observed in GF-mice. Bacterial community profiling revealed an increase in variants belonging to the families Lachnospiraceae and Clostridium cluster XIVa in mice 8 days post-infection with H. diminuta, and the transfer of feces from these mice suppressed DNBS-colitis in GF-mice. Mice treated with a bacteria-free filtrate of feces from H. diminuta-infected mice were protected from DNBS-colitis. Metabolomic analysis revealed increased acetate and butyrate (both or which can reduce colitis) in feces from H. diminuta-infected mice, but not from antibiotic-treated H. diminuta-infected mice. H. diminuta-induced protection against DNBS-colitis was not observed in ffar2−/− mice. Immunologically, anti-il-10 antibodies inhibited the anti-colitic effect of H. diminuta-infection. Analyses of epithelial cell lines, colonoids, and colon segments uncovered reciprocity between butyrate and il-10 in the induction of the il-10-receptor and butyrate transporters. Conclusion Having defined a feed-forward signaling loop between il-10 and butyrate following infection with H. diminuta, this study identifies the gut microbiome as a critical component of the anti-colitic effect of this helminth therapy. We suggest that any intention-to-treat with helminth therapy should be based on the characterization of the patient’s immunological and microbiological response to the helminth.
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    Infection with Hymenolepis diminuta Is More Effective than Daily Corticosteroids in Blocking Chemically Induced Colitis in Mice
    (2009-11-30) Melon, Alexandra; Wang, Arthur; Phan, Van; McKay, Derek M.
    Purpose. To compare infection with the tapeworm, Hymenolepis diminuta, with steroid (dexamethasone) administration in the inhibition of dinitrobenzene sulfonic acid- (DNBS-) induced colitis in mice. Procedures. Mice were treated with DNBS ± infected with H. diminuta or treated with daily dexamethasone (2 mg/Kg, ip.) and were assessed 72 hours post-DNBS by the calculation of disease activity and histological damage scores, and spleen cell cytokine production. Results. H. diminuta-infected mice showed increased IL-4 and IL-10 production by spleen cells compared to other groups and were protected from DNBS-induced colitis. In contrast, there was little benefit of dexamethasone in the treatment of colitis. Collagen deposition in the colon was not different between the groups. Conclusions. H. diminuta was superior to dexamethasone in the prevention of DNBS-induced colitis and did not result in additional side effects (i.e., collagen deposition). Comparisons with current therapeutics and long-term followup to studies are essential if “helminth therapy” is to become a viable treatment for specific inflammatory diseases in the gut or other tissues.