Helminths and the Microbiome: An Anti-Inflammatory Partnership

It isn’t often that I find new research on helminths and equally rare to find one on the interactions of the various species of resident in the gut, so I was particularly pleased to find an actual human clinical study looking at how the presence of helminths affects the microbiome and the immune response.[i]

The authors point out in their introduction that, “Diseases of modernity, such as allergy, autoinflammatory, and metabolic diseases are increasingly observed in industrialized countries,”…and that the loss of helminths which “may have protective effects against autoinflammatory diseases,” are suspect as a major cause.

One study they point out that I found particularly interesting:  transferring the microbiota from mice infected with a helminth to mice without helminths actually protected the latter group from allergic airway inflammation.  Studies such as this imply that a part of the protection against inflammation afforded by helminths is through their beneficial effect on the bacterial microbiome. Unfortunately, there are no such studies as yet in humans.

This paper though is at least a start.

66 people in Indonesia, where helminth are endemic, took part in this randomized, placebo-controlled study.  At the start the trial, stool was tested to look at both bacterial content and to test for the presence of helminths. 40 of these people had helminths at the start of the trial; 4 species of helminth were found (Ascaria lumbricoides, hookworm (Necator americanus), Ancylostoma duodenale and Trichuris trichuria (whipworm).  Some people had more than one species. The patients also had blood taken.  For 21 months, in a randomized fashion, anti-helminth drugs were given to those in the experimental group (the control did received a placebo) every 3 months, and stool and blood were taken, to look at changes in bacterial makeup and cytokine levels.

I was not at all surprised by the results:  “When subjects were free of helminth infection…increasing proportions of Bacteroidetes was associated with lower levels of IL-10 response to LPS…This association was significantly diminished when subjects were helminth-infected…”

That is, higher levels of Bacteroidetes were found in those without helminths.  This family of bacteria, when proportionally too high, appear to depress regulatory cytokine levels (IL-10 is a major one) so that, when challenged with a bacterial toxin (LPS is lipopolysaccharides, a highly inflammatory toxin produced by certain bacteria), the patients had markedly higher levels of inflammation.

“IL-10 was already marked as a key anti-inflammatory cytokine involved in the induction of immune suppression by helminths.  Our observation that helminths counteract the suppressed IL-10 response to LPS in subjects with higher Bacteroidetes proportions supports the so called “old friends hypothesis”…stating that certain infectious agents such as helminths may have protective effects against immune dysfunction and inflammatory diseases…”

There is a lot more interesting information in this paper but this is the main takeaway:  helminths appear to positively affect the bacterial content of the human digestive system and thus, both directly and indirectly (by boosting levels of regulatory cytokines) keep the inflammatory system in check.

By the way, if this topic is of particular interest to you, I highly recommend spending a few minutes reading at least these other two posts (hereand here) on this site.  (There are many more articles on the subject but I tried to pick two highlights!)  While of course much more research needs to be done, the evidence is pretty damn overwhelming at this point:  the loss of our native macrobiomes is a really bad thing.

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[i] Martin, I, et. al. The effect of gut microbiome composition on human immune response: an exploration of interference by helminth infections.  Frontiers in Genetics. 2019;10(1028).