by Lancaster University

High fat diet induced obesity protects mice from chronic T. muris infection. Percentage change in basal start weight in wild-type C57BL/6 mice receiving 12 weeks of CD or HFD prior to a single (A) or trickle (B) low dose T. muris infection (arrows indicate dose strategy); (C) representative image of macroscopic weight gain in single dose infected mice following 12 weeks on CD/HFD. Representative H&E-stained histology images of (D) mLN adipose and (E) liver in naïve and single low dose infected mice at day 42 post-infection following 12 weeks CD/HFD; arrows indicate adipose cell crowning. Worm burdens counted from the caecum and proximal colon in mice following a CD/HFD after receiving a single (F) or trickle (H) low dose infection. (G) Fecal egg counts at weeks 8 and 9 following a trickle T. muris infection in mice on CD/HFD. Data (n=4-11 mice per group) are from two to three independent experiments performed. *, P<0.05; **, P<0.01; ***, P<0.005, I, N, and § indicates significant weight change between CD and HFD of infected, naïve or both groups respectively; N.S., not significant via Bonferonni’s multiple comparison following ANOVA (F) and (G) and Mann-Whitney U-test (A), (B) and (H) for indicated comparisons between groups. Credit: Mucosal Immunology (2023). DOI: 10.1016/j.mucimm.2023.01.004

Scientists have discovered that a high-fat diet allows the immune system to eliminate a parasitic worm which is a major cause of death and illness in the developing world.

Parasitic worms affect up to a billion people, particularly in developing nations with poor sanitation. One of these parasites known as "whipworm" can cause long lasting infections in the large intestine.

Researchers from Lancaster University and the University of Manchester have discovered that a high-fat diet allows the immune system to eliminate the parasite.

Lead author Dr. Evelyn Funjika, formerly at Manchester and now at the University of Zambia, said, "Just like the UK, the cheapest diets are often high in fat and at-risk communities to whipworm are increasingly utilizing these cheap diets. Therefore, how worm infection and western diets interact is a key unknown for developing nations.

"In order to be able to study how nutrition affects parasite worm infection, we have been using a mouse model, Trichuris muris, closely related to the human whipworm Trichuris trichiura and seeing how a high-fat diet impacts immunity."

It has been previously shown that immune responses which expel the parasite rely on white blood cells called T-helper 2 cells, specialized for eliminating gastrointestinal parasites.

The findings, published in the journal Mucosal Immunology, demonstrate how a high-fat diet, rather than obesity itself, increases a molecule on T-helper cells called ST2 and this allows an increased T-helper 2 response which expels the parasite from the large intestinal lining.

Dr. John Worthington from the Department of Biomedical and Life Science at Lancaster University co-led the research.

"We were quite surprised by what we found during this study. High-fat diets are mostly associated with increased pathology during disease. However, in the case of whipworm infection this high fat diet licenses the T-helper cells to make the correct immune response to expel the worm."

Co-lead Professor Richard Grencis from the University of Manchester said, "Our studies in mice on a standard diet demonstrate that ST2 is not normally triggered when expelling the parasite, but the high-fat diet boosts the levels of ST2 and hence allows expulsion via an alternative pathway."

Co-lead Professor David Thornton from the University of Manchester added, "It was really fascinating that simply altering the diet completely switched the immune response in the gut from one that fails to expel the parasite, to one that brings about all the correct mechanisms to eliminate it."

However, Dr. Worthington added caution to the findings.

"Before you order that extra take-away, we have previously published that weight loss can aid the expulsion of a different gut parasite worm. So these results may be context specific, but what is really exciting is the demonstration of how diet can profoundly alter the capacity to generate protective immunity and this may give us new clues for treatments for the millions who suffer from intestinal parasitic infections worldwide."

More information: Evelyn Funjika et al, High fat diet induced resistance to helminth infection via alternative induction of Type 2 immunity, Mucosal Immunology (2023). DOI: 10.1016/j.mucimm.2023.01.004

Provided by Lancaster University