Probiotic administration ameliorates helminth exacerbation of colitis

INTRODUCTION: Historically, Inflammatory Bowel Disease (IBD) was
thought of as a disease of high-income countries (HIC) such as the USA,
where 1-3 million people are estimated to suffer from IBD. However, as lowmiddle income countries (LMIC) become more westernized they are exposed
to a number of risk factors for IBD, including diet change and smoking.
Importantly, these LMIC regions also have a high burden of infectious
diseases, including gastrointestinal parasite helminths that may impact on
disease. Helminth infection is reported to both exacerbate and alleviate IBD,
however one consensus on how helminths modify disease is lacking.
METHODS: This study makes use of a well-defined model of murine colitis
(IBD) and a natural parasite of mice Heligmosomoides polygyrus
(H.polygyrus) to test how helminth infection alters the incidence of IBD.
BALB/c mice were infected with 200 H.polygyrus L3 larvae for either 7 or 28
days. Dextran Sulfate Sodium (DSS) colitis was induced through the
administration of the DSS chemical in drinking water for 7 days, after which
the mice were put back on normal drinking water for 3 days. The probiotic
VSL#3 was administered in drinking water ad libitum during helminth infection.
RESULTS: We demonstrate that helminth infection exacerbates DSS colitis .
Infection with H.polygyrus is associated with increased colon inflammation as
well as increased systemic inflammation, including splenomegaly and
neutrophilia. This heightened systemic inflammation is characterised by
significant bacterial translocation to the spleen, significant shifts in bacterial
composition and a loss in intestinal epithelial integrity. Exacerbation of DSS
colitis is dependent on host gender, host specific pathogen free (SPF) status
and the dose of H.polygyrus infective larvae but is independent of the phase
of H.polygyrus infection. The administration of probiotics during helminth
infection restored epithelial integrity, significantly reduced bacterial
translocation to the spleen, ameliorated splenomegaly and reduced helminth
exacerbation of DSS colitis.
CONCLUSION: Our work uncovers an unexpected and novel role for live
helminth infection in exacerbating IBD and suggests that helminth-induced
dysbiosis of the microbiota may drive exacerbation. These studies reveal
restoration of the microbiota through probiotics as a potential therapy for the treatment of gastrointestinal inflammatory disorders.