Gut flora may impact susceptibility to Konzo neurological diseases, caused by growing cassava
Differences between species and microbiome genes in children in different regions of the Democratic Republic of the Congo (DRC) may affect the release of cyanide after consuming poorly processed cassava and impact the development of konzo neurological disorder, according to a study of 180 children, carried out by researchers at Children’s National Hospital.
Konzo, a serious and irreversible motor neuron disease that causes paralysis, can occur after consuming improperly processed cassava (Manihot esculenta Crantz) a cassava root that represents a food security crop for more than half a billion people in the developing world. Recently published research indicates that children living in areas at high risk for konzo have high glucosidase (linamarase) and low rhodanesi microbes in their gut, which could mean greater sensitivity and less protection against the disease. konzo.
The researchers suggest their recently published study is the first to shed light on the gut microbiome of populations that depend on poisonous cassava as their primary food source. “Knowing who is most at risk could lead to targeted interventions to better treat cassava or try to diversify the diet,” said Eric Vilain, MD, PhD, director of the Center for Genetic Medicine Research at Children’s National. “An alternative intervention is to modify the microbiome to increase the level of protection. However, this is a difficult task that can have unintended consequences and other side effects. “
Vilain is co-main author and co-author of the article published by the team in Genetics of nature, which is titled “The Gut Microbiome in the Konzo” and in which the authors concluded: “Our results indicate that the structure of the gut microbiome is highly variable depending on the region of sampling, but most interestingly, we identify enrichments unique bacterial species and functional pathways that potentially modulate konzo susceptibility in prone regions of Congo.
The DRC is one of the least developed countries in the world, and a high percentage of people depend on a monotonous diet of cassava for their basic survival. However, poorly processed cassava contains linamarin, a cyanogenic compound. Enzymes with glucosidase activity work to convert starch into simple sugars, but they also break down linamarin, which then releases cyanide in the body. “Consuming improperly processed foods derived from bitter cassava, which contains high levels of cyanogenic compounds such as linamarin, can lead to non-progressive irreversible motor neuron disease known as konzo, which manifests primarily in children and women of childbearing age, ”the authors explained. . “The occurrence of konzo is strongly associated with the consumption of poorly processed bitter cassava, associated with malnutrition and environmental stressors such as drought and periods of turbulence, leading to irreversible spastic paralysis and neurocognitive deficit. “
But while some risk factors, such as food insecurity, chronic malnutrition, and particularly the lack of sulfur amino acids, are associated with konzo outbreaks, “… the team continued.
To understand the influence of detrimental subsistence on gut flora and its relationship to this debilitating multifactorial neurological disease, researchers compared gut microbiome profiles in 180 children in the DRC using metagenomic shotgun sequencing. This approach assesses bacterial diversity and detects the abundance of microbes and microbial genes in various environments.
The samples were collected in Kinshasa, an urban area with a diversified diet and without konzo; Masi-Manimba, a rural area with a predominantly cassava-based diet and a low prevalence of konzo; and Kahemba, a predominantly cassava-based food region with a high prevalence of konzo. “Few populations in the world depend exclusively on toxic foods for survival, making the DRC a unique country to question the influence of detrimental subsistence on the intestinal flora and its relation to this debilitating multifactorial neurological disease,” added the scientists.
They first examined the structure of the gut microbiome in relation to urban and rural settings and found that, regardless of region, all study groups were home to an average of more than 450 unique species. Further, investigators wrote: “Although all groups appear to harbor a diverse microbiome structure, many differences were detected when comparing the profiles of individuals from Kinshasa to those residing in Masi-Manimba or Kahemba. The results indicated that for their study populations, there were “regional specifications and influences” that contributed to the overall structure of the gut flora, “outside of a simple urban versus rural context.”
While the results indicated an enrichment in bacteria capable of hydrolyzing linamarin, as well as genes encoding -D-glucosidase, in the children of Kahemba, the authors also pointed out that the development of konzo is multifactorial in nature with many factors. many environmental variables and stressors. “As such, the gut microbiome may not be the sole cause of disease, but rather a required modulator, because without a functioning gut microbiome, linamarin and other cyanogenic glycosides would pose little or no risk to it. ‘man,’ they concluded.
Matthew S. Bramble, PhD, researcher at Children’s National, commented: “While the gut microbiome is not the only cause of disease as the environment and malnutrition play a role, it is a required modulator. Simply put, without gut microbes, linamarin and other cyanogenic glucosides would pose little or no risk to humans.
“This study overcame many challenges related to research in low-resource settings,” said Desire Tshala-Katumbay, MD, MPH, PhD, FANA, co-lead author and expert scientist at the National Institute for Biomedical Research in Kinshasa, DRC, and professor of neurology at Oregon Health & Science University. “This will open up new avenues to prevent konzo, a devastating disease for many children in sub-Saharan Africa. “
For the next steps, the researchers aim to study sibling pairs from konzo-prone regions of Kahemba, where only one sibling is affected by the disease. “Studying siblings will help us control factors that cannot be controlled otherwise, such as cassava preparation in the household,” said Neerja Vashist, research fellow at Children’s National. “In this work, each sample had approximately 5 million DNA reads each, so for our follow-up, we plan to increase this figure to over 40 million reads per sample and the overall size of the study cohort. . This study design will allow us to confirm that the trends we have observed hold on a larger scale, while improving our ability to comprehensively characterize the gut microbiome.