Immunological Consequences of Intestinal Fungal Dysbiosis

Abstract

Compared to bacteria, the role of fungi within the intestinal microbiota is poorly understood. In this study we investigated whether the presence of a “healthy” fungal community in the gut is important for modulating immune function. Prolonged oral treatment of mice with antifungal drugs resulted in increased disease severity in acute and chronic models of colitis, and also exacerbated the development of allergic airway disease. Microbiota profiling revealed restructuring of fungal and bacterial communities. Specifically, representation of Candida spp. was reduced, while Aspergillus, Wallemia, and Epicoccum spp. were increased. Oral supplementation with a mixture of three fungi found to expand during antifungal treatment (Aspergillus amstelodami, Epicoccum nigrum, and Wallemia sebi) was sufficient to recapitulate the exacerbating effects of antifungal drugs on allergic airway disease. Taken together these results indicate that disruption of commensal fungal populations can influence local and peripheral immune responses and enhance relevant disease states.

Candida albicans Pathogenesis: Fitting within the Host-Microbe Damage Response Framework

“…However, more recent clinical studies examining fecal loads have demonstrated increased Candida levels with antibotic treatment (101). Overgrowth may facilitate localized mucosal infection and/or generalized GI tract disturbances, but the validity of GI candidiasis via overgrowth as a clinical entity is controversial (102,103). This has been difficult to verify due to the lack of specific symptoms (belching, bloating, indigestion, nausea, diarrhea, and gas) and lack of diagnostic tests.…”

Immunity against fungi

“…In a house dust mite-induced airway allergy model, disruption of the gut fungal community with antifungal drugs increased disease severity (181). Aspergillus amstelodami, Epicoccum nigrum, and Wallemia sebi increased in abundance during antifungal drug-induced fungal dysbiosis, and intestinal supplementation with these strains replicated the detrimental effects of antifungal drugs on lung allergy (181).…”

CX3CR1 + mononuclear phagocytes control immunity to intestinal fungi

“…Fungi are present in the mammalian intestine (1–5), yet little is known about their ability to influence immune homeostasis. The recent advances in deep sequencing technologies have redefined our understanding of the fungal communities (mycobiota) colonizing the mammalian barrier surfaces(2).…”