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

Abstract

Chagas disease is caused by the flagellate protozoan Trypanosoma cruzi. Cardiomyopathy and damage to gastrointestinal tissue are the main disease manifestations. There are data suggesting that the immune response to T. cruzi depends on the intestinal microbiota. We hypothesized that Chagas disease is associated with an altered gut microbiome and that these changes are related to the disease phenotype. The stool microbiome from 104 individuals, 73 with Chagas disease (30 with the cardiac, 11 with the digestive, and 32 with the indeterminate form), and 31 healthy controls was characterized using 16S rRNA amplification and sequencing. The QIIME (Quantitative Insights Into Microbial Ecology) platform was used to analyze the data. Alpha and beta diversity indexes did not indicate differences between the groups. However, the relative abundance of Verrucomicrobia, represented primarily by the genus Akkermansia, was significantly lower in the Chagas disease groups, especially the cardiac group, compared to the controls. Furthermore, differences in the relative abundances of Alistipes, Bilophila, and Dialister were observed between the groups. We conclude that T. cruzi infection results in changes in the gut microbiome that may play a role in the myocardial and intestinal inflammation seen in Chagas disease.

Loss of QKI in macrophage aggravates inflammatory bowel disease through amplified ROS signaling and microbiota disproportion

“…The 16S sequencing analysis of microorganisms further disclosed the dramatic proportional changes in the microbiota genus. The latter genus is known to lead the result of anti-inflammatory effects in the host, as reported previously 42 . All in all, our results highly suggest that the disproportional changes of the microbiota directly affect the severity of IBD phenotype by enhancing the ROS stress in the epithelial layers.…”

Targeting the Gut Microbiota in Chagas Disease: What Do We Know so Far?

“…Another study employing next generation sequencing (NGS) to investigate the gut microbiota composition of one hundred and fourteen Brazilian individuals with different forms of chronic CD also confirmed that T. cruzi triggers human gut microbiota changes ( De Souza-Basqueira et al, 2020 ). In this study, thirty patients had the cardiac form, eleven had the digestive form, thirty-two had the indeterminate form and thirty-one were healthy individuals.…”

“…Indeterminate CD patients had lowered Bacteroidaceae family (phylum Bacteroidetes), specifically Bacteroides genera when compared to controls. Patients with digestive form of CD and megacolon had reduction in Lachnospiraceae family but increase in Porphyromonadaceae family (phylum Bacteroidetes) ( De Souza-Basqueira et al, 2020 ).…”

“…Interestingly, recent evidence now suggests an involvement of other biological factors that may contribute to mechanisms underpinning CD pathophysiology. For instance, the role of the gut microbiota in CD has been reported by preclinical and clinical studies ( Duarte et al, 2004 , 2005 ; McCall et al, 2018 ; Robello et al, 2019 ; De Souza-Basqueira et al, 2020 ). Gut microbiota alterations have been found in triatomine insects, mice, and human hosts ( Duarte et al, 2004 , 2005 ; Garcia et al, 2007 ; Díaz et al, 2016 ; McCall et al, 2018 ; Robello et al, 2019 ).…”

Molecular and Clinical Aspects of Chronic Manifestations in Chagas Disease: A State-of-the-Art Review

“…Another interesting factor that has drawn attention of researchers in the past decade is the gut dysbiosis caused by CD. It has been hypothesized that a relationship between the patient's microbiome and the phenotype of the chronic form of CD exists [195,196]. For instance, De Souza-Basqueira et al [196] performed a stool microbiome analysis in 104 chronic CD patients with differing phenotypes (including cardiac, GI, and indeterminate) and compared them with that of 31 controls.…”