Contribution of diet to the composition of the human gut microbiota

This paper is part of the Proceedings from the 2013 ENGIHR Conference in Valencia, Spain. More papers from this supplement can be found at http://www.microbecolhealthdis.net Microbial Ecology in Health & Disease 2015. © 2015 Daniela Graf et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported License (http://creativecommons.org/licenses/by-nc/3.0/), permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. ACKNOWLEDGEMENTS The authors acknowledge the support of the European Science Foundation (ESF), in the framework of the Research Networking Programe, The European Network for Gastrointestinal Health Research.Peer reviewedPublisher PD

A Novel Probiotic Mixture Exerts a Therapeutic Effect on Experimental Autoimmune Encephalomyelitis Mediated by IL-10 Producing Regulatory T Cells

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). One potential therapeutic strategy for MS is to induce regulatory cells that mediate immunological tolerance. Probiotics, including lactobacilli, are known to induce immunomodulatory activity with promising effects in inflammatory diseases. We tested the potential of various strains of lactobacilli for suppression of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. METHODOLOGY/PRINCIPAL FINDINGS: The preventive effects of five daily-administered strains of lactobacilli were investigated in mice developing EAE. After a primary screening, three Lactobacillus strains, L. paracasei DSM 13434, L. plantarum DSM 15312 and DSM 15313 that reduced inflammation in CNS and autoreactive T cell responses were chosen. L. paracasei and L. plantarum DSM 15312 induced CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) in mesenteric lymph nodes (MLNs) and enhanced production of serum TGF-beta1, while L. plantarum DSM 15313 increased serum IL-27 levels. Further screening of the chosen strains showed that each monostrain probiotic failed to be therapeutic in diseased mice, while a mixture of the three lactobacilli strains suppressed the progression and reversed the clinical and histological signs of EAE. The suppressive activity correlated with attenuation of pro-inflammatory Th1 and Th17 cytokines followed by IL-10 induction in MLNs, spleen and blood. Additional adoptive transfer studies demonstrated that IL-10 producing CD4(+)CD25(+) Tregs are involved in the suppressive effect induced by the lactobacilli mixture. CONCLUSIONS/SIGNIFICANCE: Our data provide evidence showing that the therapeutic effect of the chosen mixture of probiotic lactobacilli was associated with induction of transferable tolerogenic Tregs in MLNs, but also in the periphery and the CNS, mediated through an IL-10-dependent mechanism. Our findings indicate a therapeutic potential of oral administration of a combination of probiotics and provide a more complete understanding of the host-commensal interactions that contribute to beneficial effects in autoimmune diseases

Influence of Leptin and Adiponectin Supplementation on Intraepithelial Lymphocyte and Microbiota Composition in Suckling Rats

Dietary components in early life play a role in both microbiota and intestinal immune system maturation in mammalian species. Adipokines, as endogenously produced hormones from breast milk, may have an impact on this process. The aim of the present study was to establish the influence of leptin and adiponectin supplementation during suckling on the intraepithelial lymphocyte composition, intestinal barrier function, intestinal gene expression, and gut microbiota in rat. For this purpose, newborn Wistar rats were supplemented daily with leptin, adiponectin, or whey protein concentrate during the first 21 days of life. Lymphocyte composition was established by immunofluorescence staining and flow cytometry analysis; intestinal gene expression by real-time PCR and cecal microbiota were analyzed through 16S rRNA gene sequencing. Although leptin and adiponectin were able to increase the Tc TCRαβ+ and NKT cell proportion, they decreased the NK cell percentage in IEL. Moreover, adipokine supplementation differentially modified CD8+ IEL. While the supplementation of leptin increased the proportion of CD8αα+ IEL (associated to a more intestinal phenotype), adiponectin enhanced that of CD8αβ+ (related to a peripheral phenotype). Furthermore, both adipokines enhanced the gene expression of TNF-α, MUC-2, and MUC-3, and decreased that of FcRn. In addition, the adipokine supplementations decreased the abundance of the Proteobacteria phylum and the presence of Blautia. Moreover, leptin-supplemented animals had lower relative abundance of Sutterella and a higher proportion of Clostridium genus, among others. However, supplementation with adiponectin resulted in lower abundance of the Roseburia genus and a higher proportion of the Enterococcus genus. In conclusion, the supplementation with leptin and adiponectin throughout the suckling period had an impact on both the IEL composition and the gut microbiota pattern, suggesting a modulatory role of these adipokines on the development of intestinal functionality

Impact of the gut microflora on the digestive system in the suckling rat

The postnatal development of the gastrointestinal (GI) system in mammals is genetically programmed, but is, to an unknown extent, regulated by external factors such as the diet and the gut microflora. These factors can influence the growth of the GI tract, the age-related pattern of appearance of digestive enzymes and the decreased intestinal macromolecular permeability at gut closure, normally timed with weaning in young rodents. The main focus of this doctoral thesis was to elucidate the effect of the colonizing gut microflora as well as to clarify the impact of the maternal microflora on the GI development in rat pups using pro-, pre- and antibiotic manipulations. The suckling rat model was chosen, because the rat is born immature enabling manipulations during its GI development. A probiotic bacterium, Lactobacillus plantarum 299v (Lp299v), having significant health effects in humans and animals and E. coli (CCUG 29300T), an opportunistic bacterium of the family Enterobacteriaceae, as well as broad spectrum antibiotics or a prebiotic inulin preparation, Synergy1, were administered, either directly by gavage to rat pups at various ages during the suckling period, or via the rat dam by administering bacteria or antibiotics in the drinking water. Taken together the results showed that manipulating the gut microflora, either directly or via the mother, affected the growth and function of the GI tract and its associated organs in suckling rats. The effect of Lp299v was age-dependent, where pups colonized early after birth or being offspring born from dams consuming the bacterium showed the greatest impact on the gut function. An altered maternal bacterial flora, induced by antibiotic treatment and E. coli exposure of dams, transfers to the offspring with increased cecal densities of Enterobacteriaceae in the rat pups, which affected the GI development. Moreover, the pups of dams treated with antibiotics showed a delayed stomach development, while the pups of E. coli dams showed an increased growth of the GI system. Increased blood levels of haptoglobin, indicating inflammation, were observed in both groups of pups, which was not seen in the Lp299v exposed pups. Thus, the effects on the GI system are not likely merely mediated by inflammation. Stimulation of the endogenous microflora, by feeding a fiber preparation, enhanced intestinal growth and function in suckling rats. Abstract _________________________________________________________________________ The results obtained in this thesis broaden the knowledge of the impact of specific bacterial groups for growth and function of the digestive system and can hopefully be applied for the care of neonates. The fact that increased numbers of Enterobacteriaceae during the suckling period leads to inflammation might improve our understanding of the “hygiene hypothesis” and the pathogenesis of inflammatory and immune-related bowel diseases in neonates

The gut microbiota : A predisposing factor in obesity, diabetes and atherosclerosis

The cluster of pathologies comprising the metabolic syndrome (MetS) includes increased waist circumference, hyperglycemia, elevated blood pressure and hyperlipidemia. With time, these conditions present a major risk of developing obesity, type 2 diabetes and atherosclerosis. Fecal microbiota transplant (FMT) experiments performed in mice have given an intriguing foundation for a microbial-based therapy of obesity in humans. In the years 2004 - 2009, Gordon and colleagues presented ground-breaking studies on the role of the gut microbiota in host energy metabolism and proposed the hypothesis that obesity alters the composition of bacteria in the gut. Lipopolysaccharides (LPS) is a component of Gramnegative bacteria cell walls and is pro-inflammatory through activation of Toll-like receptor 4 (TLR4) on antigen-presenting cells located both in the gut and in other tissues in the body. Diabetes mellitus (DM) presents in two major forms: type I and type II, characterized by vastly different molecular events leading up to malfunction of glucose homeostasis