Th17 responses and natural IgM antibodies are related to gut microbiota composition in systemic lupus erythematosus patients.

Intestinal dysbiosis, characterized by a reduced Firmicutes/Bacteroidetes ratio, has been reported in systemic lupus erythematosus (SLE) patients. In this study, in vitro cultures revealed that microbiota isolated from SLE patient stool samples (SLE-M) promoted lymphocyte activation and Th17 differentiation from naïve CD4(+) lymphocytes to a greater extent than healthy control-microbiota. Enrichment of SLE-M with Treg-inducing bacteria showed that a mixture of two Clostridia strains significantly reduced the Th17/Th1 balance, whereas Bifidobacterium bifidum supplementation prevented CD4(+) lymphocyte over-activation, thus supporting a possible therapeutic benefit of probiotics containing Treg-inducer strains in order to restore the Treg/Th17/Th1 imbalance present in SLE. In fact, ex vivo analyses of patient samples showed enlarged Th17 and Foxp3(+) IL-17(+) populations, suggesting a possible Treg-Th17 trans-differentiation. Moreover, analyses of fecal microbiota revealed a negative correlation between IL-17(+) populations and Firmicutes in healthy controls, whereas in SLE this phylum correlated directly with serum levels of IFNγ, a Th1 cytokine slightly reduced in patients. Finally, the frequency of Synergistetes, positively correlated with the Firmicutes/Bacteroidetes ratio in healthy controls, tended to be reduced in patients when anti-dsDNA titers were increased and showed a strong negative correlation with IL-6 serum levels and correlated positively with protective natural IgM antibodies against phosphorylcholine.

Phenolic compounds from red wine and coffee are associated with specific intestinal microorganisms in allergic subjects.

The dietary modulation of gut microbiota, suggested to be involved in allergy processes, has recently attracted much interest. While several studies have addressed the use of fibres to modify intestinal microbial populations, information about other components, such as phenolic compounds, is scarce. The aim of this work was to identify the dietary components able to influence the microbiota in 23 subjects suffering from rhinitis and allergic asthma, and 22 age- and sex-matched controls. The food intake was recorded by means of an annual food frequency questionnaire. Dietary fibre tables were obtained from Marlett et al., and the Phenol-Explorer database was used to assess the phenolic compound intake. The quantification of microbial groups was performed using an Ion Torrent 16S rRNA gene-based analysis. The results showed a direct association between the intake of red wine, a source of stilbenes, and the relative abundance of Bacteroides, and between the intake of coffee, rich in phenolic acids, and the abundance of Clostridium, Lactococcus and Lactobacillus genera. Despite epidemiological analyses not establishing causality, these results support the association between polyphenol-rich beverages and faecal microbiota in allergic patients.

Human colon-derived soluble factors modulate gut microbiota composition.

The commensal microbiota modulates immunological and metabolic aspects of the intestinal mucosa contributing to development of human gut diseases including inflammatory bowel disease. The host/microbiota interaction often referred to as a crosstalk, mainly focuses on the effect of the microbiota on the host neglecting effects that the host could elicit on the commensals. Colonic microenvironments from three human healthy controls (obtained from the proximal and distal colon, both in resting conditions and after immune - IL-15- and microbiota - LPS-in vitro challenges) were used to condition a stable fecal population. Subsequent 16S rRNA gene-based analyses were performed to study the effect induced by the host on the microbiota composition and function. Non-supervised principal component analysis (PCA) showed that all microbiotas, which had been conditioned with colonic microenvironments clustered together in terms of relative microbial composition, suggesting that soluble factors were modulating a stable fecal population independently from the treatment or the origin. Our findings confirmed that the host intestinal microenvironment has the capacity to modulate the gut microbiota composition via yet unidentified soluble factors. These findings indicate that an appropriate understanding of the factors of the host mucosal microenvironment affecting microbiota composition and function could improve therapeutic manipulation of the microbiota composition.

Association of polyphenols from oranges and apples with specific intestinal microorganisms in systemic lupus erythematosus patients.

Our group has recently shown the existence of a gut microbial dysbiosis in systemic lupus erythematosus (SLE), supporting previous evidence involving intestinal bacteria in the initiation and amplification of autoimmune diseases. While several studies have addressed the use of dietary fibres to modify intestinal microbiota, information about other correlated components, such as polyphenols, is scarce. The aim of this work was to identify dietary components able to influence this altered microbiota in 20 SLE women and 20 age-matched controls. Food intake was recorded by means of a food frequency questionnaire. The intake of fibres was calculated from Marlett tables, and Phenol-Explorer was used for polyphenol consumption. Results showed positive associations between flavone intake and Blautia, flavanones and Lactobacillus, and dihydrochalcones and Bifidobacterium in the SLE group. Regarding the controls, dihydroflavonols were directly associated with Faecalibacterium, whereas flavonol intake was inversely associated with Bifidobacterium. From the food sources of these polyphenols related to microbiota, orange intake was directly associated with Lactobacillus and apple with Bifidobacterium in SLE, whilst red wine was the best contributor to Faecalibacterium variation. The association between common foods and particular microbial genera, reported to be decreased in SLE, could be of great importance for these patients.

Association of levels of antibodies from patients with inflammatory bowel disease with extracellular proteins of food and probiotic bacteria.

Inflammatory bowel disease (IBD) is an autoimmune disease characterized by a chronic inflammation of the gastrointestinal tract mucosa and is related to an abnormal immune response to commensal bacteria. Our aim of the present work has been to explore the levels of antibodies (IgG and IgA) raised against extracellular proteins produced by LAB and its association with IBD. We analyzed, by Western-blot and ELISA, the presence of serum antibodies (IgA and IgG) developed against extracellular protein fractions produced by different food bacteria from the genera Bifidobacterium and Lactobacillus. We used a sera collection consisting of healthy individuals (HC, n = 50), Crohn's disease patients (CD, n = 37), and ulcerative colitis patients (UC, n = 15). Levels of IgA antibodies developed against a cell-wall hydrolase from Lactobacillus casei subsp. rhamnosus GG (CWH) were significantly higher in the IBD group (P < 0.002; n = 52). The specificity of our measurements was confirmed by measuring IgA antibodies developed against the CWH peptide 365-VNTSNQTAAVSAS-377. IBD patients appeared to have different immune response to food bacteria. This paper sets the basis for developing systems for early detection of IBD, based on the association of high levels of antibodies developed against extracellular proteins from food and probiotic bacteria.