Commensal-pathogen interactions in the intestinal tract

Abstract

The intestinal microbiota are pivotal in determining the developmental, metabolic and immunological status of the mammalian host. However, the intestinal tract may also accommodate pathogenic organisms, including helminth parasites which are highly prevalent in most tropical countries. Both microbes and helminths must evade or manipulate the host immune system to reside in the intestinal environment, yet whether they influence each other’s persistence in the host remains unknown. We now show that abundance of Lactobacillus bacteria correlates positively with infection with the mouse intestinal nematode, Heligmosomoides polygyrus, as well as with heightened regulatory T cell (Treg) and Th17 responses. Moreover, H. polygyrus raises Lactobacillus species abundance in the duodenum of C57BL/6 mice, which are highly susceptible to H. polygyrus infection, but not in BALB/c mice, which are relatively resistant. Sequencing of samples at the bacterial gyrB locus identified the principal Lactobacillus species as L. taiwanensis, a previously characterized rodent commensal. Experimental administration of L. taiwanensis to BALB/c mice elevates regulatory T cell frequencies and results in greater helminth establishment, demonstrating a causal relationship in which commensal bacteria promote infection with an intestinal parasite and implicating a bacterially-induced expansion of Tregs as a mechanism of greater helminth susceptibility. The discovery of this tripartite interaction between host, bacteria and parasite has important implications for both antibiotic and anthelmintic use in endemic human populations.

Helminth infections and gut microbiota – a feline perspective

“…Lactobacilli are members of the lactic acid bacteria, a large group of autochthonous microbes in the gut of humans and animals and that are especially known for their probiotic properties [41]. Interestingly, populations of lactobacilli are expanded in the duodenum of C57BL/6 mice following infection with H. polygyrus , while the opposite was observed in the microbiota of infected BALB/c mice, which are relatively resistant to the infection [12]. In addition, a positive correlation was observed between the burden of H. polygyrus infection in BALB/c mice and the abundance of lactobacilli in the duodenum of these rodents, which was linked to expansion of Treg cells by the gut-associated lymphoid tissue and production of IL-17A by cells in the mesenteric lymph nodes (MLN) in response to helminth infection [12].…”

Changes in duodenal tissue-associated microbiota following hookworm infection and consecutive gluten challenges in humans with coeliac disease

“…In particular, given the primary role played by gastrointestinal dysbiosis in the pathogenesis of CeD12, it has been proposed that one of the mechanisms by which hookworms can support intestinal immune homeostasis in inflammatory disorders (such as CeD), is via the alteration of the composition of the gut microbiota and relative abundance of individual microbial species81314151617. This hypothesis is based on the results of recent studies by us and others, in which experimental infections with gastrointestinal helminths were accompanied by detectable changes in commensal bacterial composition of both human and animal hosts131417181920, as well as of the metabolic profiles of bacterial communities which indirectly promote the development of host regulatory T-cell responses21. In our previous study, experimental hookworm infection of human volunteers with CeD and administration of progressively increasing doses of dietary gluten resulted in maintenance of the composition of the gut flora, as determined from faecal samples from these subjects14.…”

Enteric nematodes and the path to up-regulation of type 2 cytokines IL-4 and IL-13

“…Enteric parasitic nematode infection has been linked to prevention of type 1 diabetes, experimental autoimmune encephalomyelitis, Graves' disease, collagen-induced arthritis and inflammatory bowel disease (IBD) [86], protection against allergies [87,88], improvement of symptoms in IBD [37,38], and attenuation of the effects of multiple sclerosis [89,90] and bacterial sepsis [91]. The beneficial effects of nematode infection in these autoimmune and inflammatory pathologies may be derived from actions of their products on immune cells, up-regulation of IL-4/IL-13 and other Th2 associated cytokines and associated down-regulation of proinflammatory Th1/Th17 profiles, or beneficial shifts in the abundance of relative distribution of microbiota [91][92][93].…”