Diabetes study successfully uses hookworm to combat disease

Live hookworms could be the answer to combating metabolic disease, with a world-first Australian trial proving the infection is both safe and successful.
 
Published in Nature Communications, the double-blind clinical trial saw 40 people with early warning signs of cardiovascular disease or type 2 diabetes inoculated with either 20 or 40 larvae, or a placebo.
 
After two years of observation, many infected patients saw significant improvements in their metabolic health, improved insulin resistance, and enhancements in their overall mood.
 
The microscopic necator americanus larvae proved so beneficial, all but one participant decided to keep their worms after two years rather than take deworming medication.
 
The research team from James Cook University’s Australian Institute of Tropical Health and Medicine now wants to launch a larger-scale international trial, sparked by their success.
 
Lead researcher Dr Doris Pierce told newsGP the study yielded some ‘very exciting’ results, opening the door to the further investigation.
 
‘The results from our proof-of-concept study are certainly encouraging and confirm previous findings in human observational and experimental mouse studies that helminth infection, or a worm-derived product, could be a beneficial preventive intervention in humans at risk of type 2 diabetes,’ she said.
 
The research came about following evidence of reduced prevalence of insulin resistance and type 2 diabetes in countries with endemic parasitic worm infections.
 
Previous studies have suggested hookworms release proteins into their host to control the immune system and safeguard their survival.
 
‘Worm-infected populations generally enjoy better metabolic health and the removal of the worms following mass-deworming generally resulted in worsened metabolic status,’ Dr Pierce said.
 
‘Experimental studies in animal models of obesity and diabetes have also consistently reported improved glycaemic control and reduced body mass in the infected animals, but causal evidence in humans was missing.’
 
The trial found those infected with 20 hookworms experienced a median Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) level drop from a pre-trial level of 3.0 units to just 1.8 units.
 
Body mass was also reduced for those with 20 worms after two years.
 
Changes in mood were an added benefit for researchers, who noticed ‘remarkable’ changes in patients, despite testing in the first wave of the COVID-19 pandemic.
 
‘While we currently don’t have an explanation for this observation, it is not unheard of [for] parasites to affect their host’s behaviour,’ Dr Pierce said.
 
‘Serotonin, another critical neurotransmitter in the central nervous system and associated with many psychiatric conditions, is predominantly produced in the intestine, which is also the hookworm’s residence, establishing at least a potential connection between hookworms and mood.’
 
It is not the first time an infection of hookworms has been studied for its health benefits.
 
Previous studies both locally and internationally have determined the larvae’s success, to varying degrees, in helping those with coeliac disease, inflammatory bowel disease and asthma.
 
For the Australian researchers, the success of this new trial advances the possibility of designing protein-based treatments which mimic the effects of the live worm.
 
Moving forward, Dr Pierce said a wider trial is needed to confirm their proof of concept.
 
‘While our findings are favourable, our sample sizes were small and involved mostly Caucasian females, which limits our ability to make firm conclusions and generalise our findings,’ she said.
 
‘We are hoping to confirm our results in a future trial involving a greater number of participants of diverse backgrounds that might also allow us to optimise hookworm doses and gain some mechanistic understanding.
 
‘Many questions still remain before the treatment could become mainstream.’
 
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Diabetes metabolic T2D