Dietary Yeasts Reduce Inflammation in Central Nerve System via Microflora

Abstract

ObjectivesThe intestinal microflora affects the pathogenesis of several autoimmune diseases by influencing immune system function. Some bacteria, such as lactic acid bacteria, have been reported to have beneficial effects on immune function. However, little is known about the effects of yeasts. Here, we aimed to investigate the effects of various dietary yeasts contained in fermented foods on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), and to elucidate the mechanisms underlying these effects.MethodsThe effects of eight yeasts selected from 18 types of yeasts contained in fermented foods were examined using an EAE model. Of these, Candida kefyr was investigated by analyzing the intestinal microflora and its effects on intestinal and systemic immune states.ResultsAdministration of C. kefyr ameliorated the severity of EAE. Reduced numbers of Th17 cells, suppressed interleukin (IL)-6 production by intestinal explants, and increased Tregs and CD103-positive regulatory dendritic cells in mesenteric lymph nodes (MLNs) were observed. Analysis of 16s-rDNA from feces of C. kefyr-treated mice demonstrated increased Lactobacillales and decreased Bacteroides compared to control flora. Transfer of intestinal microbiota also resulted in decreased Bacteroides and ameliorated symptoms of EAE. Thus, oral administration of C. kefyr ameliorated EAE by altering the microflora, accompanied by increased Tregs and CD103-positive regulatory dendritic cells in MLNs and decreased Th17 cells in the intestinal lamina propria.InterpretationOral ingestion of C. kefyr may have beneficial effects on MS by modifying microflora. In addition, our findings also suggested the potential health benefits of dietary yeasts.

Commensal Fungi in Health and Disease

“…It has also been reported in an animal model that S. boulardii interacts with and alters commensal bacterial microbiota (Yu et al, 2017) (Figure 1). Similarly, a recent study demonstrated that oral administration of the dietary yeast Candida kefyr (also known as Candida pseudotropicalis or Kluyveromyces marxianus ) was protective in mouse models of colitis and experimental autoimmune encephalomyelitis (Takata et al, 2015). This was accompanied by alterations in the bacterial microbiota, and transfer of the microbiota into new animals could confer protection that was associated with an increase in mesenteric lymph node regulatory T cells and reduction in lamina propria Th17 cells.…”

Reply to comment on: Dietary yeasts reduce inflammation in central nervous system via microflora

“…In our study, oral administration of C. kefyr reduced the proportion of Bacteroides and microbiome transfer from C. kefyr ‐treated mice reduced the proportion of Bacteroides and ameliorated EAE and dextran sulfate sodium‐induced colitis. However, oral administration of S. cerevisiae did not reduce the proportion of Bacteroides or clinical severities in both animal models 2. These results suggested that modification of microbiome by C. kefyr reduced inflammation.…”

“…Diet, intestinal microflora, and metabolites produced by this microflora are important because they exert positive effects on human health through intestinal immunity. Several bacteria and their components exert positive effects against experimental autoimmune encephalomyelitis (EAE); however, limited information is available on the effects of yeasts such as Saccharomyces , Candida , and Aspergillus , which are constituents of fermented foods, on EAE 2. Our study is significant because we found that Candida kefyr ameliorated EAE; in addition, our study suggested that not all yeasts exerted the same effect on immunity, as mentioned by Perricone et al Furthermore, the effects of C. kefyr seem to be some immune‐mediated diseases specifically depending on the underlying pathology.…”

Comment on: Dietary yeast reduce inflammation in central nerve system via microflora

“…may have revealed the importance of different dietary yeast in contribution to inflammation and autoimmunity. From one side, it is possible that some types (such as Saccharomyces boulardii ) can be used as probiotics acting in a microbiome competition model leading to amelioration of autoimmune conditions 1. Nonetheless, it is fundamental to address the exact role of those types which, on the contrary, may even worsen an autoimmune/inflammatory condition.…”

“…We recently read with great interest the article on the possible immunomodulatory effects of dietary yeast, specifically Candida kefir, on the central nervous system, notably the experimental autoimmune encephalomyelitis (EAE) mouse model by Takata et al 1 The role of yeast in inflammatory and autoimmune phenomena is nowadays controversial. 2 The experiment from Takata et al raises an important observation that not all yeast lead to the same effect on immunity.…”