<p><i>Trypanosoma cruzi</i> parasites are responsible for causing Chagas disease. These agents can infect different organ systems, thereby leading to tissue injury and proliferation. The digestive tract form of disease is associated with perturbations in nutrient assimilation, intestinal trafficking and excretion. Next-generation sequencing revealed the role of microorganisms in the development of Chagas disease. Alterations in the microbial community due to <i>T. cruzi</i> in vectors and hosts have been linked to a reduced immune response against the parasite, guiding the organization and development of infection. These microbial changes are associated with provocative and neuropsychiatric ailments and comorbid illnesses. <i>Lactobacillus</i> sp. is a native genus in humans that shows mutualistic relationships with the host and is involved in proper gut function. Recent studies based on the role of these genera have also explained their role as psychobiotics. A detailed study is needed to determine the changes in the gut microbiome in patients and how to treat this disease effectively with lesser-known side effects using lactobacilli as a prime choice.</p> Graphical abstract <p></p>