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Host–Microbial Interactions in the Gut – Implications for Child Health
Some genes associated with susceptibility to IBD encode proteins involved Conclusion
in host–microbial interactions.
55
These include Nod2/CARD15
26,27
and Microbes and humans have co-evolved to develop multiple routes of
Nod1/CARD4,
56
as well as the recently described autophagy-related genes communication. These interactions generally result in a co-operative state
ATG16L1 and IRGM.
57,58
Patients with Crohn’s disease develop antibodies of symbiosis, where both bugs and host benefit and co-exist. The host
against bacterial antigens, such as CBir1, flagellin and the outer benefits from the wide repertoire of metabolic functions (or
membrane porin OmpC.
59,60
Taken together, these data support a critical ‘metabotypes’) available through the diversity of functional microbial
role for microbes in the development of IBD. genes.
66
In some circumstances, however, bacteria acquire genes
encoding virulence determinants. Under these conditions, the colonised
Functional Gastrointestinal Disorders host develops signs of disease, even though in many cases it remains
Emerging data support the utility of probiotics for the treatment of unclear whether the arising clinical symptoms serve to benefit the host or
common functional disorders associated with dysbiosis, including, for the pathogen. Genetically determined factors guide host responses to
example, colic in infants
61
and irritable bowel syndrome in older children infection. Failure to mount an appropriate protective response to
and adults.
62
Further studies are still required before these modalities can pathogens leads to severe disease and, ultimately, death of the host. In
be incorporated into routine practice.
63
contrast, an inappropriately exaggerated immune response leads to the
development of chronic inflammatory conditions, such as IBD.
46
For these
Other Conditions reasons, understanding the determinants of the host response to bacteria
Animal studies implicate a role for intestinal microbes in extra-intestinal with either virulence or protective potential is of critical importance in
conditions, including obesity and type 1 diabetes. The microbiome of developing novel strategies to promote human health. ■
‘Western diet’-fed mice contributes to weight gain, since transplantation
of the microbiota of obese mice into germ-free rodents results in Acknowledgements
increased body fat.
22
A similar association between the diet, microbiome Research in the authors’ laboratory is supported by a Fay Shapiro Cutler
and obesity was also described in human subjects.
64
Non-obese diabetic operating grant from the Crohn’s and Colitis Foundation of Canada
mice that also lack the adaptor protein MyD88 are protected from the (CCFC) and the Canadian Institutes of Health Research (CIHR). EW is
development of insulin-dependent diabetes in the presence of intestinal supported by a fellowship award from the CIHR/Canadian Association of
microbes, whereas germ-free animals are affected.
65
Although these Gastroenterology (CAG)/AstraZeneca partnership and by a University of
studies support a role for microbes in the pathogenesis of complex Toronto Faculty of Medicine Postgraduate Award. MG is supported by a
chronic disorders, many of the involved underlying mechanisms remain to post-doctoral fellowship award from CIHR/CAG/CCFC. PS is the recipient
be determined. of a Canada Research Chair in Gastrointestinal Disease.
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