Parasitic Infection May Lead to Positive Metabolic Outcomes in Humans

Infection with certain parasitic worms may lead to positive changes in metabolic outcomes and some type 2 diabetes (T2D) parameters, according to research results published in Frontiers in Endocrinology.

To date, there has been only 1 meta-analysis of data on the absence of inflammatory-based disease in populations endemic to parasitic worms, or helminths, although there are a growing number of publications reporting this finding. In the current systematic review and meta-analysis, researchers sought to review the most recent published evidence to evaluate the role of helminth infection on metabolic outcomes and glucose metabolism in humans.

A total of 903 potential references were identified; after the exclusion of duplicates and application of inclusion criteria, a total of 14 studies were included in the review, 11 of which were included in the meta-analysis. Thirteen studies were of high quality, and 1 did not meet the cutoff and was excluded from the meta-analysis but was included in the systematic review. Ten studies were cross-sectional in nature, 2 were case control, and 2 were cohort studies. Studies were conducted in 11 countries and included sample sizes ranging from 158 to 9939.

Three studies evaluated the effect of previous parasitic infection on glucose homeostasis, while 11 reportedly evaluated the effect of active infection. Assessed helminths included Schistosoma japonicum, Opisthorchis viverrini, Strongyloides stercoralis, Schistosomiasis mansoni, Schistosoma spp and any worm/multiple infection. Infections were primarily diagnosed via stool examination/microscopy, serology, or polymerase chain reaction (PCR) testing.

All studies measured at least 1 marker relevant to glucose homeostasis, including fasting blood glucose, glycated hemoglobin (HbA_1c), fasting plasma insulin, homeostasis model assessment of insulin resistance (HOMA-IR), T2D diagnosis, and metabolic syndrome diagnosis.

Of the 14 studies included in the systematic review, 9 reported that parasitic worm infection demonstrated protective effects on diabetes-related parameters, with 3 studies reporting a positive association between specific infections and T2D diagnosis and 2 studies finding no association.

Within the 7 studies measuring fasting blood glucose, 5 provided sufficient data for meta-analysis inclusion. The pooled data from these studies showed a significant decrease in fasting blood glucose in those with parasitic infections, while a subgroup analysis by parasite genus showed that infection with soil-transmitted nematode had no effect on fasting blood glucose compared with uninfected people. Conversely, there was a significant decrease in fasting blood glucose in those infected with Schistosoma spp. vs those not infected. The largest beneficial impact was reported in those with active S. mansoni infections. Infections with either S japonicum or Schistosoma spp had only a modest effect.

Six studies measured HbA_1c but only 3 had sufficient data for meta-analysis inclusion. Two studies evaluated the effect of infection with trematode parasites while the remaining study examined intestinal nematode infection. These studies indicated that active infection with O.viverrini or previous infection with Schistosoma spp was associated with a significantly lowered HbA_1c.

Pooled data showed no difference in HbA_1c between those with and without infections, although a trend toward lower HbA_1c was identified.

Studies that evaluated metabolic syndrome were conducted in patients with previous infection with Schistosome parasites. Metabolic syndrome prevalence was 56% lower in these infected populations.

Pooled data from 3 studies compared T2D prevalence in infected vs noninfected individuals and demonstrated no difference in T2D prevalence. Results of a subgroup analysis, though, showed that T2D prevalence was 46% lower in those infected with Schistosoma spp.

A negative association between testing positive for infection and T2D prevalence was evidence, according to the researchers.

Study limitations include those inherent to systematic reviews and meta-analyses, a lack of consistency in outcomes across studies, and no detailed knowledge of individual, patient-level infection history.

“Despite the limitations of our meta-analysis, the overall results clearly showed that infection with intestinal worms…was less efficacious than the tissue dwelling parasites S. mansoni and O. viverrini,” the researcher concluded. “[We] strongly support the proposal that helminth parasites have the capacity to regulate obesity driven inflammation to mediate a positive effect on metabolic outcomes. However, considerations for the variations between different parasites and a deeper understanding of the mechanisms involved is required before helminth-based therapies can progress to the clinic.”

Reference

Rennie C, Fernandez R, Donnelly S, McGrath K. The impact of helminth infection on the incidence of metabolic syndrome: a systematic review and meta-analysis. Front Endocrinol. 2021;12:728396. doi:10.3389/fendo.2021.728396