Helminths and the gut microbiota

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    Helminths and bacteria form a complex, interactive ecosystem involved in immunity

    The gut and its inhabitants should be considered a complex ecosystem, not only involving bacteria but also parasites, not just sitting together but interacting. (Prof Richard Grencis, Manchester University) [1]
    It is like a three-legged stool - the microbes, worms and immune system regulate each other. The worms have been with us throughout our evolution and their presence, along with bacteria, in the ecosystem of the gut is important in the development of a functional immune system. (Prof Ian Roberts, Manchester University) [2]
    Our findings show that murine intestinal helminth infection not only alters the intestinal bacterial communities but that intestinal bacteria contribute to the ability of helminth infection to attenuate allergic airway inflammation. (Zaiss, et al) [3]
    We also saw significant possible beneficial changes on gut microbiota with hookworm infection. [4]
    Our findings uncover the intricate interactions of the tripartite partnership within the helminth–microbiome–host complex. It is evident that the ability of the helminth to modulate the immune system depends, at least in part, on the intestinal microflora, and this interaction in turn may impact its protective effect in inflammatory disease. [5]

    Scientific papers and articles relating to helminths and the gut microbiota


    The results of this study demonstrate that helminths release molecules via their excretory-secretory pathway that have broad-spectrum bactericidal activity.
    A tissue-dwelling helminth was shown to drive expansions of host colonic Tregs through the gut microbiota, with an increase in L. reuteri and short-chain fatty acids, suggesting that the gut microbiome serves as a critical component of anti-inflammation effects, even with therapy using an extraintestinal helminth.


    Human microbiome members, Peptostreptococcaceae, a family of Gram-positive bacteria in the class Clostridia, have been found to display a superior capacity to promote the life cycle of whipworm species, including hatching of eggs from Trichuris trichiura (TTO).
    Subjects colonized by helminths showed higher gut bacterial diversity than helminth-negative individuals in an indigenous Malaysian cohort.
    "The data indicate that helminth infections… altered the abundance of specific bacterial taxa in the host gut but not overall bacterial diversity. In contrast, the saliva microbiota displayed both altered bacterial richness and abundance during active helminth infections."
    "While most of (the helminths) (e.g., Ascaris sp. and Trichuris sp.) can modify the gut microbiota, others (such as N. americanus) appear not to influence it."


    This study provides strong evidence that helminth infection dynamically shifts the intestinal microbiome structure, with those helminths found in the large intestine, such as Enterobius vermicularis and Trichuris trichiura, showing the greatest influence on microbiome composition.
    “Extrapolating from this model system, we suggest that for helminth therapy to be beneficial it needs to be coupled to a precise knowledge of the immunological profile of the malady to be treated and the composition of the patients’ microbiome. Furthermore, we speculate that reduced efficacy of helminth therapy could be enhanced by combination with a probiotic matched to compensate for dysbiosis in a particular individual.”
    Supports previous evidence suggesting that the presence of intestinal parasites is linked to strong bacterial microbiota community changes.
    Proposes that microbiota-derived extracellular vesicles might be key players in host-helminth-microbiome crosstalk.
    This study reveals data linking colonisation by the hookworm, NA, with modulation of host bacterial microbiota composition.
    Factors such as the widespread use of antibiotics, chronic inflammation and the loss of complex eukaryotic symbionts such as helminths, cause dramatic alterations in the gut ecosystem and drive rapid change in microorganisms via Darwinian evolution to create functionally distinct bacteria that may potentially have properties of pathogens but yet are difficult to distinguish from their benign predecessors.
    “Our findings uncover the intricate interactions of the tripartite partnership within the helminth–microbiome–host complex. It is evident that the ability of the helminth to modulate the immune system depends, at least in part, on the intestinal microflora, and this interaction in turn may impact its protective effect in inflammatory disease.”
    "These results suggest that Schistosoma japonicum infection has a significant effect on microbiome composition characterized by a higher abundance of the TM7 phylum and development of a Bacteroides enterotype."


    Increased numbers of helminth co-infections, in particular with the gut-resident soil-transmitted helminths, were significantly associated with increased bacterial diversity which, in general, is associated with a healthy gut.


    There is considerable interplay between helminths, micronutrients and the microbiota on the regulation of immune responses in humans.
    The modulation of the immune system by helminths involves an interplay with several other factors, such as diet and environment, in addition to being influenced by the composition of the gut microbiome.
    This work provides conclusive evidence that intestinal helminths can impact the mammalian intestinal microbiome, and indicates that helminth-induced changes can occur at regions distant from the site of parasite infection.
    Helminths prevented weight gain in laboratory mice on a high-fat diet. They did this by boosting populations of bacteria - notably certain species of Bacillus and Escherichia - that produce compounds which trigger increased energy consumption.
    This study contributes to understanding of how microbial communities differ between individuals infected by soil-transmitted helminths and those who are uninfected.
    In a very detailed “Helminths” section (pages 26-35), this paper discusses evidence that host-associated microbes may impact helminth infection success, that helminth colonization may impact the diversity and composition of the gut microbiome, and that both can have impacts on immune function.


    Trichuris suis and dietary inulin co-operatively mediate beneficial changes in microbiota composition in pigs to enhance anti-inflammatory immune responses.
    Monospecific, chronic infection with the helminth, S. stercoralis, were found to be associated with global shifts in the composition of the human faecal microbiota, as well as subtle changes in faecal metabolic profiles.
    The helminth, A. suum, uses a variety of factors with broad-spectrum antibacterial activity to affirm itself within its microbe-rich environment in the gut.
    While this study focused on the parasites, Dientamoeba fragilis and Blastocystis, rather than helminths, its conclusions are nevertheless interesting.
    “Presence of parasites was associated to a rich and diverse microbiome in healthy controls and individuals with unspecific GI symptoms… Observations of parasite colonization being associated to healthy features of the gut microbiome should differentiate our view of intestinal parasites beyond the focus on pathogenicity.”
    This is a good review of studies investigating the interactions of the intestinal microbiota, gut parasites and their host, and how these interactions may affect the overall health of the host.
    The eggs of T. muris that hatch in sterile conditions are free from bacteria.
    T. muris maintains its own distinct microbiota, comprising bacteria selected from the intestine of its host, regardless of the surrounding bacterial populations.
    Infection with T. muris causes significant restructuring of the host cecal microbiota and a reduction in total bacterial diversity.
    T. muris-induced changes in the host microbiota suppresses subsequent parasite egg hatching, consequently controlling parasite numbers in the infected host intestine independently of the host adaptive immune system.


    Highlights findings concerning responses to bacterial stimuli, antimicrobial peptides and the reciprocal influences between nematodes and their environmental bacteria. Also discussed are the microbiota of nematodes and alterations in the intestinal microbiota of mammalian hosts by helminth infections.
    Demonstrates that an intestinal helminth infection can have remote protective antiviral effects in the lung through induction of a microbiota-dependent type I interferon response.


    Helminth infection protects mice deficient in the Crohn’s disease susceptibility gene Nod2 from intestinal abnormalities by inhibiting colonization with an inflammatory Bacteroides species.
    Discusses at length the interrelationships between intestinal helminths and microbiota, in both humans and mice, and highlights the fact that certain microbiota species can determine the outcomes of helminth infection.
    "... although intestinal helminths are generally accepted to possess potent immuno-modulatory activity, it is unknown whether this capacity requires interactions with intestinal bacteria. We propose that this 'ménage à trois' situation is likely to have exerted a strong selective pressure on the development of our metabolic and immune systems."


    Helminths and bacterial microbiota act in bi-directional synergy to modulate immune responses.
    Helminths move the balance of the intestinal flora to favour “probiotic” microorganisms.
    "Notably, we observed a significant increase in microbial species richness over the course of the trial, which could represent a potential mechanism by which hookworms can regulate gluten-induced inflammation and maintain intestinal immune homeostasis."
    "Dynamic interactions between the host and gastrointestinal microbiota play an important role for local and systemic immune homeostasis."
    "In general, helminth presence is linked with high microbiota diversity, which may confer health benefits to the host… The most pronounced helminth-microbiota association was between the presence of tapeworms in the small intestine and increased S24-7 (Bacteroidetes) family in the stomach."
    "In this article, we review recent progress in the elucidation of host-parasite-microbiota interactions in both animal models of chronic inflammation and humans, and provide a working hypothesis of the role of the gut microbiota in helminth-induced suppression of inflammation."
    Colonisation by Hymenolepis diminuta led to several changes in rat cecal microbiome that were mostly within the Firmicutes phylum, involved about 20% of the total bacteria, and entailed a shift from Bacilli to Clostridia species.
    "... infection of T. muris causes a significant and substantial impact on intestinal microbiota and digestive function of mice with affects in long term immune regulation."


    Hookworm infection produces a minor increase in microbial species richness, but has no detectable effect on community structure, diversity or relative abundance of individual bacterial species. (NB. Testing was done at only 8 weeks, so the worms were not yet fully engaged.)
    “… helminth-induced immunomodulation occurs independently of changes in the microbiota but is dependent on Ym1.”
    Discusses changes occurring in the microbiota upon helminth infection and the underlying mechanisms leading to these changes.
    Helminths may have an impact on the diversity, bacterial community structure and function of the gut microbiota.
    Some bacteria and nematode-trapping fungi form mutually beneficial relationships to victimise nematodes.
    The bacterium, B. animalis, significantly decreased the S. venezuelensis worm burden and egg output.


    "… by inducing an immune response that includes IL-22, intestinal helminths may enhance the mucosal barrier function of the intestinal epithelium. This may restore the mucosal microbiota populations from dysbiosis associated with colitis and improve intestinal homeostasis."


    Whipworms can restore the balance of gut bacterial communities in sick monkeys.


    Some probiotic strains have been shown to be effective in controlling some species of parasitic worm. NB. This study was not concerned with helminths used in therapy, but other types of parasite.


    Helminth infection shifts the composition of intestinal bacteria.
    "It is like a three-legged stool - the microbes, worms and immune system regulate each other. The worms have been with us throughout our evolution and their presence, along with bacteria, in the ecosystem of the gut is important in the development of a functional immune system."