Helminth Interactions with Bacteria in the Host Gut Are Essential for Its Immunomodulatory Effect

Jirků, Milan; Lhotská, Zuzana; Frgelecová, Lucia; Kadlecová, O; Petrželková, Klára J.; Morien, Evan; Jirků-Pomajbíková, Kateřina

doi:10.3390/microorganisms9020226

Cited by 4 publications

(6 citation statements)

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“…Mechanistic studies to understand how infection with helminth parasites inhibits inflammatory disease have implicated suppression of Th1 immunity or production of immunoregulatory cells and mediators [4,13,14,36]. This focus on host immunological processes, while intuitive, has, until recently, overlooked the potential involvement of the host microbiota as a regulator of mucosal immunity and gut homeostasis [22,[37][38][39]. Following identification that infection with H. diminuta significantly increased bacterial species richness in mice (e.g., increased relative abundance of Lachnospiraceae [25] and reduced Bacteroidaceae, members of which may exert a pro-colitigenic effect [40]), treatment with broadspectrum antibiotics was found to prevent the inhibition of colitis evoked by H. diminuta-infection.…”

Section: Discussionmentioning

confidence: 99%

Cooperation between host immunity and the gut bacteria is essential for helminth-evoked suppression of colitis

Shute

Callejas

et al. 2021

Microbiome

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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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Section: Discussionmentioning

confidence: 99%

Cooperation between host immunity and the gut bacteria is essential for helminth-evoked suppression of colitis

Shute

Callejas

et al. 2021

Microbiome

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“…An increase in Firmicutes, 89 particularly Clostridia 85,88,90,97–99 and Lactobacilli, 86,91,93,95,101 is commonly observed. Other studies show an increase in Bacteroides 87,91,92,96,100 . Use of Stat6 KO mice has revealed shifts in the microbiome are primarily caused by the Th2 effector functions 90,91 .…”

Section: The Microbiomementioning

confidence: 97%

“…85 Despite this, some overall conclusions can be drawn. Intestinal helminths, including H. polygyrus, [85][86][87][88][89][90][91] T. muris, 90,[92][93][94] T. suis, 95 H. diminuta, 96,97 A. ceylanicum, 98 N. brasiliensis 99 and S. venezuelensis, 100,101 do significantly alter the host's microbiome. This can involve an increase 85,87 or decrease 90,93,94,96,98 in microbial diversity, or more specific changes in the abundance of individual taxa.…”

Section: Microbiome Shifts In Preclinical Modelsmentioning

confidence: 99%

“…Intestinal helminths, including H. polygyrus, [85][86][87][88][89][90][91] T. muris, 90,[92][93][94] T. suis, 95 H. diminuta, 96,97 A. ceylanicum, 98 N. brasiliensis 99 and S. venezuelensis, 100,101 do significantly alter the host's microbiome. This can involve an increase 85,87 or decrease 90,93,94,96,98 in microbial diversity, or more specific changes in the abundance of individual taxa. An increase in Firmicutes, 89 particularly Clostridia 85,88,90,[97][98][99] and Lactobacilli, 86,91,93,95,101 is commonly observed.…”

Section: Microbiome Shifts In Preclinical Modelsmentioning

confidence: 99%

“…Other studies show an increase in Bacteroides. 87,91,92,96,100 Use of Stat6 KO mice has revealed shifts in the microbiome are primarily caused by the Th2 effector functions. 90,91 This finding is confirmed by similar changes in the microbiome observed when recombinant IL-4 or IL-13 is administered to mice.…”

Section: Microbiome Shifts In Preclinical Modelsmentioning

confidence: 99%

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Helminths' therapeutic potential to treat intestinal barrier dysfunction

Mules

Inns

Gros

2023

Allergy

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The intestinal barrier is a dynamic multi‐layered structure which can adapt to environmental changes within the intestinal lumen. It has the complex task of allowing nutrient absorption while limiting entry of harmful microbes and microbial antigens present in the intestinal lumen. Excessive entry of microbial antigens via microbial translocation due to ‘intestinal barrier dysfunction’ is hypothesised to contribute to the increasing incidence of allergic, autoimmune and metabolic diseases, a concept referred to as the ‘epithelial barrier theory’. Helminths reside in the intestinal tract are in intimate contact with the mucosal surfaces and induce a range of local immunological changes which affect the layers of the intestinal barrier. Helminths are proposed to prevent, or even treat, many of the diseases implicated in the epithelial barrier theory. This review will focus on the effect of helminths on intestinal barrier function and explore whether this could explain the proposed health benefits delivered by helminths.

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