Gut microbiota disturbance during helminth infection: can it affect cognition and behaviour of children?

Soil-transmitted helminth (STH) infections such as Ascaris lumbricoides, Trichuris trichiura and hookworms affect more than a third of the world’s population, with the heaviest worm burdens occurring in non-industrialized countries [1]. STH,infections are associated with significant morbidity, particularly in children; infection is recognised to cause nutritional deficits, with clinical and physical consequences including anaemia and reduced growth [2‐5]. In addition to their nutritional effects, soil-transmitted helminth infections are also reported to impair cognitive function [6‐8], limit educational advancement, and as a result, hinder economic development [9]. The effects of helminth infections, particularly by hookworms, on cognitive development of children were first reported by Waite and Neilson in 1919 [10]. Since then, there have been several studies that looked at the effects of STH infections on different domains of cognitive function. Nevertheless, at present, available evidence is conflicting. A recent update of the Cochrane review concluded that there is little or no evidence that cognitive function is affected by STH infections [11, 12], but some have argued that trials included in the Cochrane review were of poor quality to measure effects [13] and that STH effects on cognition could even be greater than initially suggested [3]. Several observational studies (some not included in the meta-analysis by the Cochrane review) reviewed in [13] reported that STH infections impair the efficiency of cognitive processes including memory, learning, verbal fluency and non-verbal intelligence [6‐8, 14‐17]. In addition, investigations into STH infections during pregnancy have also demonstrated an association with poor cognitive and motor development in infants [18, 19].

Multiple mechanisms have been demonstrated to explain STH-induced nutritional impairment in infected individuals: a loss of iron and protein through feeding on host tissues [20], an increasing malabsorption of nutrients [5], a competition for vitamin A in the intestine [21], or diarrhoea and dysentery [22]. Conversely, the pathophysiological pathways by which STH infections contribute to altered intellectual performance reported by some studies are still subject to significant debate. Some of the cognitive effects of STH infection can be partly explained by the direct effect of observed nutritional deficits on the brain and the indirect effect of pathophysiological events occurring in the gut environment where STH reside; the relative importance of these competing mechanisms remain unclear.

While available evidence in favour of the helminth-microbiota-CNS hypothesis is circumstantial, the recent debate around helminth associated morbidity indicate the need for further research to elucidate the mechanisms through which gastrointestinal helminth infections induce cognitive developmental morbidity. Future studies looking at the effect on STH on childhood cognitive developmental domains should be adequately powered to measure effects that are likely to be subtle. In addition future studies should considered validated tools for measuring cognitive morbidity effects; these need to be sensitive enough to detect quantitative changes in the microbiota and longitudinal study designs will be paramount to quantify the effects on each element of the system. Combining metagenomic output with comprehensive psychometric tests constitutes an important direction for future work.