Oral Administration of Lactobacillus helveticus LA401 and Lactobacillus gasseri LA806 Combination Attenuates Oesophageal and Gastrointestinal Candidiasis and Consequent Gut Inflammation in Mice

Abstract

Candida albicans is an opportunistic pathogen that causes mucosal gastrointestinal (GI) candidiasis tightly associated with gut inflammatory status. The emergence of drug resistance, the side effects of currently available antifungals and the high frequency of recurrent candidiasis indicate that new and improved therapeutics are needed. Probiotics have been suggested as a useful alternative for the management of candidiasis. We demonstrated that oral administration of Lactobacillus gasseri LA806 alone or combined with Lactobacillus helveticus LA401 in Candida albicans-infected mice decrease the Candida colonization of the oesophageal and GI tract, highlighting a protective role for these strains in C. albicans colonization. Interestingly, the probiotic combination significantly modulates the composition of gut microbiota towards a protective profile and consequently dampens inflammatory and oxidative status in the colon. Moreover, we showed that L. helveticus LA401 and/or L. gasseri LA806 orient macrophages towards a fungicidal phenotype characterized by a C-type lectin receptors signature composed of Dectin-1 and Mannose receptor. Our findings suggest that the use of the LA401 and LA806 combination might be a promising strategy to manage GI candidiasis and the inflammation it causes by inducing the intrinsic antifungal activities of macrophages. Thus, the probiotic combination is a good candidate for managing GI candidiasis by inducing fungicidal functions in macrophages while preserving the GI integrity by modulating the microbiota and inflammation.

Anticandidal Activities by Lactobacillus Species: An Update on Mechanisms of Action

“…In vivo studies in animal models –particularly in mice- show that lactobacilli can reduce Candida burdens and reverse dysbiosis. Candida -induced stomach lesions, gastric inflammation, and dysbiosis in murine models are attenuated by several species, i.e., L. rhamnosus [ 126 ], L. gasseri, L. helveticus [ 127 ], and L. pentosus [ 128 ], among others. Lactobacilli may also act as prophylactic agents.…”

“…Authier et al showed that combined oral administration of L. helveticus and L. gasseri reduced TNF-α, IL-1β, IL-8, and CRP inflammatory markers while increasing the expression of IL-1ra and IL-10 anti-inflammatory markers in colonic tissues of C. albicans -infected mice. Moreover, mRNA expression of enzymes involved in the synthesis of pro-inflammatory eicosanoids was also decreased [ 127 ]. Clinical trials also confirm the immunomodulatory properties of lactobacilli in humans.…”

Probiotic treatment causes sex-specific neuroprotection after traumatic brain injury in mice

“…might have a neuroprotective action during the acute and chronic phases in a mouse model of TBI. Our selection was supported by literature documenting the beneficial effects of the Lactobacillus strains in various animal model studies, where modulation of the inflammatory response was a fundamental aspect of the disease process [60][61][62][63]. Different strains of Lactobacillus have been shown to decrease the production of inflammatory cytokines such as TNF-α and IL-6 [64,65], downregulate pro-apoptotic neurons, and activate inflammatory mediators [66].…”

In Vivo Efficacy of Lacticaseibacillus rhamnosus L8020 in a Mouse Model of Oral Candidiasis

“…Furthermore, animal model experiments and clinical studies provide important data regarding the efficacies of probiotics. Several animal models of oral, gastrointestinal and vaginal candidiasis have been proposed for analyses of fungal immunity and anti-fungal therapies [11,17,18,[21][22][23][24][25][26][27]. These animal models have aided in elucidating molecular mechanisms related to candidiasis; they have also facilitated the evaluation of novel therapeutic approaches.…”