Investigating associations between intestinal alterations and parasite load according to Bifidobacterium spp. and Lactobacillus spp. abundance in the gut microbiota of hamsters infected by Leishmania infantum.

BACKGROUND: Visceral leishmaniasis (VL) is a tropical neglected disease with high associated rates of mortality. Several studies have highlighted the importance of the intestinal tract (IT) and gut microbiota (GM) in the host immunological defense. Data in the literature on parasite life cycle and host immune defense against VL are scarce regarding the effects of infection on the IT and GM. OBJECTIVES: This study aimed to investigate changes observed in the colon of Leishmania infantum-infected hamsters, including alterations in the enteric nervous system (ENS) and GM (specifically, levels of bifidobacteria and lactobacilli). METHODS: Male hamsters were inoculated with L. infantum and euthanised at four or eight months post-infection. Intestines were processed for histological analysis and GM analysis. Quantitative polymerase chain reaction (qPCR) was performed to quantify each group of bacteria: Bifidobacterium spp. (Bf) and Lactobacillus spp (LacB). FINDINGS: Infected hamsters showed histoarchitectural loss in the colon wall, with increased thickness in the submucosa and the mucosa layer, as well as greater numbers of intraepithelial lymphocytes. Forms suggestive of amastigotes were seen inside mononuclear cells. L. infantum infection induced changes in ENS, as evidenced by increases in the area of colonic enteric ganglia. Despite the absence of changes in the levels of Bf and LacB during the course of infection, the relative abundance of these bacteria was associated with parasite load and histological alterations. MAIN CONCLUSIONS: Our results indicate that L. infantum infection leads to important changes in the colon and suggest that bacteria in the GM play a protective role.

Hormone levels are associated with clinical markers and cytokine levels in human localized cutaneous leishmaniasis.

Leishmaniasis is a serious health problem in several parts of the world, and localized cutaneous leishmaniasis (LCL) is the most frequent presentation of the tegumentary form of this disease cluster. Clinical presentations of leishmaniasis are influenced by both parasite and host factors, with emphasis on the host immune response. Alterations in plasma hormone levels have been described in many infections, and changes in hormone levels could be related to an imbalanced cytokine profile. In the present work, we evaluated a group of patients with LCL to determine changes in plasma hormone levels (cortisol, DHEA-S, estradiol, prolactin and testosterone) and their association with clinical markers of disease (lesion size, dose used to reach cure and time to cure) and with cytokines produced by PBMC stimulated by SLA (IFN-γ, IL-10 and TNF-α). Individuals with LCL exhibited lower plasma levels of DHEA-S, prolactin and testosterone compared with sex-matched controls, whereas levels of cortisol and estradiol were similar between patients and controls. Plasma levels of cortisol, estradiol or prolactin positively correlated with at least one clinical parameter. Cortisol and prolactin levels exhibited a negative correlation with levels of IFN-γ, whereas no correlation was observed with IL-10 or TNF-α levels. A decrease in DHEA-S levels was observed in male LCL patients when compared to male healthy controls. No other differences between the sexes were observed. Our results indicate a role for neuroendocrine regulation that restricts Th1 responses in human LCL. It is possible that, although impairing parasite killing, such neuroimmunomodulation may contribute to limiting tissue damage.