The fecal, oral, and skin microbiota of children with Chagas disease treated with benznidazole

Abstract

Background Chagas disease is still prevalent in rural areas of South America. In endemic areas of Bolivia, school children are screened for the program of Chagas disease eradication of the Ministry of Health, and positive children are treated. Here, we compared the fecal, oral and skin microbiomes of children with or without Chagas disease, and before and after benznidazol treatment of infected children. Methods A total of 543 Bolivian children (5–14 years old) were tested for Chagas disease, and 20 positive children were treated with Benznidazole. Fecal samples and oral and skin swabs were obtained before and after treatment, together with samples from a group of 35 uninfected controls. The 16S rRNA genes were sequenced and analyzed using QIIME to determine Alpha diversity differences and community distances, and linear discriminant analyses to determine marker taxa by infection status or treatment. Results Twenty out of 543 children screened were seropositive for Chagas disease (3.7%) and were included in the study, together with 35 control children that were seronegative for the disease. Fecal samples, oral and skin swabs were taken at the beginning of the study and after the anti-protozoa therapy with Benznidazole to the chagasic children. Infected children had higher fecal Firmicutes ( Streptococcus , Roseburia , Butyrivibrio , and Blautia ), and lower Bacteroides and also showed some skin -but not oral- microbiota differences. Treatment eliminated the fecal microbiota differences from control children, increasing Dialister (class Clostridia ) and members of the Enterobacteriaceae , and decreasing Prevotella and Coprococcus , with minor effects on the oral and skin bacterial diversity. Conclusions The results of this study show differences in the fecal microbiota associated with Chagas disease in children, and also evidence that treatment normalizes fecal microbiota (makes it more similar to that in controls), but is associated with oral and skin microbiota differences from control children. Since microbiota impacts in children, it is important to determine the effect of drugs on the children microbiota, since dysbiosis could lead to physiological effects which might be avoidable with microbiota restoration interventions.

3D mapping of host-parasite-microbiome interactions reveals metabolic determinants of tissue tropism and disease tolerance in Chagas disease

“…Overall, the persistence of microbiota alterations in these sites correlates well with our observation of continued alterations of the fecal microbiota and metabolome through acute and chronic experimental CD 10 . In accordance with prior reports 2010 , no significant differences in alpha-diversity were observed ( Fig. S9 ) between infected and uninfected tissue in both acute and chronic stages.…”

“…Tryptophan and tyrosine in particular were affected by infection (tryptophan: decreased in the large intestine overall, Mann-Whitney p=6.793e-06 (acute stage) and p=0.004313 (chronic stage); tyrosine: decreased in the large intestine overall, Mann-Whitney p=0.01518 (acute stage), non-significant (chronic stage)). We have previously demonstrated that experimental T. cruzi infection alters the fecal microbiome and metabolome 10 , a finding that was recently confirmed in T. cruzi- infected children in Bolivia 20 . We therefore sought to evaluate the spatial impact of T. cruzi infection on the microbiota at each collection site in acute-stage disease (except for the oesophagus where insufficient material was available to perform both metabolomic and 16S analyses), and focusing on the cecum and large intestine in chronic disease, given their role as major sites of CD pathogenesis and the unique metabolomic pattern observed at these sites ( Fig.…”

Gut Dysbiosis in Chagas Disease. A Possible Link to the Pathogenesis

“…This is the first study that has sought to describe the fecal microbiome of adult patients with the various Chagas disease phenotypes using next-generation sequencing technology. Robello et al (2019) observed a difference in the microbiota between children infected with T. cruzi and controls. In the study, children aged 5-15 years with Chagas disease had higher fecal Firmicutes (Streptococcus, Roseburia, Butyrivibrio, and Blautia), and lower Bacteroides.…”

NOD2 receptor is crucial for protecting against the digestive form of Chagas disease

“…In fact, we have previously demonstrated that those same patients have intact TLR family transcripts expression, being TLR8 overexpressed in digestive patients [ 28 ]. The microbiota dysbiosis observed in digestive chagasic patients [ 62 , 63 , 70 ] might be crucial for the elevated α-defensin levels in attempt to play its role through the formation of nanofibrils that protect intestinal mucosa from bacterial invasion [ 71 – 73 ]. Even in the absence or reduced expression of NOD2 in digestive and cardiodigestive patients, we showed that its adapter molecule RIP2 was overexpressed in those patients.…”