Lactococcus lactis Administration Modulates IgE and IL-4 Production and Promotes Enterobacteria Growth in the Gut from Ethanol-Intake Mice.

BACKGROUND: It is well known that alcohol can trigger inflammatory effects in the gastrointestinal tract (GIT), interfering with mucosal homeostasis. OBJECTIVES: This study evaluated the effectiveness of Lactococcus lactis treatment in controlling the increase in molecular biomarkers related to allergic inflammation and the effect on the diversity and abundance of the Enterobacteriaceae family in the GIT after high-dose acute administration of ethanol. METHODS: Mice received ethanol or saline solution by gavage for four consecutive days, and 24 h after the last administration, the animals were given L. lactis or M17 broth orally ad libitum for two consecutive days. The animals were subsequently sacrificed and dissected. RESULTS: L. lactis treatment was able to restore basal levels of secretory immunoglobulin A in the gastric mucosa, serum total immunoglobulin E, interleukin (IL)-4 production in gastric and intestinal tissues, and IL-10 levels in gastric tissue. L. lactis treatment encouraged the diversification of the Enterobacteriaceae population, particularly the commensal species, in the GIT. CONCLUSION: This research opens a field of studies regarding the modulatory effect of L. lactis on immunological and microbial changes induced after alcohol intake.

Hsp65-Producing Lactococcocus lactis Prevents Antigen-Induced Arthritis in Mice.

Oral tolerance is the physiological process that enables the immune system to differentiate between harmless dietary and microbiota antigens from pathogen derived antigens. It develops at the mucosal surfaces and can result in local and systemic regulatory and anti-inflammatory effects. Translation of these benefits to the clinical practice faces limitations involving specificity and doses of antigen as well as regimens of feeding. To circumvent these problems, we developed a recombinant Hsp65 delivered by the acid lactic bacteria Lactococcus lactis NCDO 2118 directy in the intestinal mucosa. Hsp65 is a ubiquitous protein overexpressed in inflamed tissues and capable of inducing immunoregulatory mechanisms. L. lactis has probiotic properties and is commonly and safely used in dairy products. In this study, we showed that continuous delivery of HSP65 in the gut mucosa by L. lactis is a potent tolerogenic stimulus inducing regulatory CD4+LAP+ T cells that prevented collagen-induced and methylated bovine serum albumin-induced arthritis in mice. Clinical and histological signs of arthritis were inhibited as well as levels of inflammatory cytokines such as IL-17 and IFN-γ, serum titers of anti-collagen antibodies and rheumatoid factor. Oral administration of L. lactis induced alterations in microbiota composition toward an increased abundance of anaerobic bacteria such as Bifidobacterium and Lactobacillus. Tolerance to HSP65 and arthritis prevention induced by the recombinant L. lactis was associated with increase in IL-10 production by B cells and it was dependent on LAP+ T cells, IL-10 and TLR2 signaling. Therefore, HSP65-producing treatment induced effective tolerance and prevented arthritis development suggesting it can be used as a therapeutic tool for autoimmune diseases.

Frontline Science: Abnormalities in the gut mucosa of non-obese diabetic mice precede the onset of type 1 diabetes.

Alterations in the composition of the intestinal microbiota have been associated with development of type 1 diabetes (T1D), but little is known about changes in intestinal homeostasis that contribute to disease pathogenesis. Here, we analyzed oral tolerance induction, components of the intestinal barrier, fecal microbiota, and immune cell phenotypes in non-obese diabetic (NOD) mice during disease progression compared to non-obese diabetes resistant (NOR) mice. NOD mice failed to develop oral tolerance and had defective protective/regulatory mechanisms in the intestinal mucosa, including decreased numbers of goblet cells, diminished mucus production, and lower levels of total and bacteria-bound secretory IgA, as well as an altered IEL profile. These disturbances correlated with bacteria translocation to the pancreatic lymph node possibly contributing to T1D onset. The composition of the fecal microbiota was altered in pre-diabetic NOD mice, and cross-fostering of NOD mice by NOR mothers corrected their defect in mucus production, indicating a role for NOD microbiota in gut barrier dysfunction. NOD mice had a reduction of CD103+ dendritic cells (DCs) in the MLNs, together with an increase of effector Th17 cells and ILC3, as well as a decrease of Th2 cells, ILC2, and Treg cells in the small intestine. Importantly, most of these gut alterations precede the onset of insulitis. Disorders in the intestinal mucosa of NOD mice can potentially interfere with the development of T1D due the close relationship between the gut and the pancreas. Understanding these early alterations is important for the design of novel therapeutic strategies for T1D prevention.

High-Salt Diet Induces IL-17-Dependent Gut Inflammation and Exacerbates Colitis in Mice.

Excess intake of sodium is often associated with high risk for cardiovascular disease. More recently, some studies on the effects of high-salt diets (HSDs) have also demonstrated that they are able to activate Th17 cells and increase severity of autoimmune diseases. The purpose of the present study was to evaluate the effects of a diet supplemented with NaCl in the colonic mucosa at steady state and during inflammation. We showed that consumption of HSD by mice triggered a gut inflammatory reaction associated with IL-23 production, recruitment of neutrophils, and increased frequency of the IL-17-producing type 3 innate lymphoid cells (ILC3) in the colon. Moreover, gut inflammation was not observed in IL-17-/- mice but it was present, although at lower grade, in RAG-/- mice suggesting that the inflammatory effects of HSD was dependent on IL-17 but only partially on Th17 cells. Expression of SGK1, a kinase involved in sodium homeostasis, increased 90 min after ingestion of 50% NaCl solution and decreased 3 weeks after HSD consumption. Colitis induced by oral administration of either dextran sodium sulfate or 2,4,6-trinitrobenzenesulfonic acid was exacerbated by HSD consumption and this effect was associated with increased frequencies of RORγt+ CD4+ T cells and neutrophils in the colon. Therefore, our results demonstrated that consumption of HSD per se triggered a histologically detectable inflammation in the colon and also exacerbated chemically induced models of colitis in mice by a mechanism dependent on IL-17 production most likely by both ILC3 and Th17 cells.

Translation and cross-cultural adaptation of the NutriQoL® questionnaire to the Portuguese language: Brazilian version / Tradução e adaptação do questionário NutriQoL® para a língua portuguesa: versão Brasileira

ABSTRACT Objective The objective of this study was to translate and cross-culturally adapt the NutriQoL® into Brazilian Portuguese. Methods The NutriQoL® comprises 17 questions that evaluate the quality of life of patients receiving home enteral nutrition therapy. The methodological procedures included the translation from the Spanish version into Portuguese by two translators, synthesis of the translations, back translation, evaluation by a committee of judges composed of 24 individuals in which a content validity index > 0.78 was considered acceptable, and generation of the pre-final version. A pre-test to analyze its semantic equivalence was administered to 12 patients receiving home enteral nutrition therapy. The final version of the questionnaire was then prepared. Results A summary version of the questionnaire was obtained using two versions of the translation. Both back translations were identical for 73.6% of sentences (n=25). Twenty-four volunteers were included in the committee of judges. The content validity index was 0.88±0.11, and 14.7% (n=5) of questions had a low content validity index and were thus reformulated. In the pre-test, 35.3% (n=12) of items obtained low levels of understanding and required adjustment. In the preparation of the final version, the inconsistencies of the items mentioned were corrected and/or adjusted. Conclusion After completing the methodological procedures, a Brazilian Portuguese version of the NutriQoL® questionnaire was obtained. Following the validation process, it can be used by dieticians and other health professionals to assess the quality of life of patients receiving home enteral nutrition therapy to contribute to improvements in care practices.

RESUMO Objetivo O intuito deste estudo foi realizar a tradução do NutriQoL para a língua portuguesa e a adaptação transcultural para o Brasil. Métodos O NutriQoL® é composto de 17 pares de perguntas que avaliam a qualidade de vida de pacientes em terapia nutricional enteral domiciliar. Os procedimentos metodológicos foram: tradução da versão em espanhol para a língua portuguesa por dois tradutores; síntese das traduções; retrotradução; avaliação, da versão traduzida, por um comitê de juízes composto por 24 indivíduos, na qual o índice de validade de conteúdo > 0,78 foi considerado, gerando a versão pré-final e realização de um pré-teste no qual a versão pré-final do questionário foi aplicada a 12 pacientes em uso de terapia nutricional enteral domiciliar para análise da equivalência semântica e elaboração da versão final do questionário. Resultados Observou-se que, a partir das duas versões traduzidas, foi possível obter uma versão síntese do questionário. As duas retrotraduções geradas foram idênticas em 73,6% das sentenças (n=25). O índice de validade de conteúdo foi 0,88 ± 0,11, e 14,7% (n=5) das questões tiveram baixo índice de validade de conteúdo, sendo então reformuladas. No pré-teste foi observado que 35,3% (n=12) dos itens obtiveram baixos índices de compreensão e necessitaram de ser reformulados. Na elaboração da versão final do questionário as inconsistências dos itens mencionados foram sanadas e/ou adaptadas. Conclusão Após conclusão dos procedimentos metodológicos, foi possível obter a versão brasileira do questionário NutriQoL® em língua portuguesa para que, após processo de validação, o instrumento seja utilizado pelo nutricionista ou demais profissionais de saúde para avaliação da qualidade de vida de pacientes em uso de terapia nutricional enteral domiciliar, a fim de contribuir com melhorias nas práticas assistenciais.