Ferreira CM , Vieira AT , Vinolo MA , Oliveira FA , Curi R , Martins Fdos S .

	Figure 1. Schematic representation of the pulmonary allergic response induced by gastrointestinal (GI) immune cells and two microbiota-related conditions (a healthy gut microbiota and a reduced gut microbiota following antibiotic treatment). Microbes in the intestines are sampled by Toll-like receptors (TLRs) on DCs either directly in the lumen or in the gut-associated lymphoid tissue (GALT). In the healthy gut microbiota, polymorphonuclear development (PMN) is normal and DCs become regulatory DCs (DCr) that promote development of Tregs and/or Th1 cells and natural killer (NK) cells. These NK cells inhibit Th2 inflammation. Antibiotic treatment kills a large proportion of healthy microbiota, leading to a reduced gut microbiota and an inflammatory environment without DCs, Th1 cells or NK cells. In this environment, an unhealthy microbiota elevates serum immunoglobulin E (IgE) levels, increases circulating basophil populations, and exacerbates basophil-mediated Th2 responses (adapted from Forsythe [110]).
	Figure 2. Schematic representation of a complex mucosal immune system composed of epithelial and hematopoietic cells that are able to react to pathogenic insults. Development of IBD occurs mainly when epithelial cells are damaged and/or the intestinal microbiota composition is not healthy.
	Figure 3. Effects of a high-fat diet. The altered microbial community of obese animals and humans promotes adiposity and decreased levels of short chain fatty acids and influences metabolic processes such as storage and metabolism of lipids in adipose tissue, muscle, and liver.

Aagaard, The placenta harbors a unique microbiome. 2014, Pubmed

Aagaard, The placenta harbors a unique microbiome. 2014, Pubmed
Abraham, Interactions between the host innate immune system and microbes in inflammatory bowel disease. 2011, Pubmed
Adams, Obesity in anaesthesia and intensive care. 2000, Pubmed
Akinbami, Asthma prevalence, health care use, and mortality: United States, 2005-2009. 2011, Pubmed
Al-Asmakh, Gut microbial communities modulating brain development and function. 2012, Pubmed
Allan, Diet and asthma: nutrition implications from prevention to treatment. 2011, Pubmed
Arpaia, Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. 2013, Pubmed
Atarashi, Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. 2013, Pubmed
Blümer, Perinatal maternal application of Lactobacillus rhamnosus GG suppresses allergic airway inflammation in mouse offspring. 2007, Pubmed
Briscoe, The orphan G protein-coupled receptor GPR40 is activated by medium and long chain fatty acids. 2003, Pubmed
Brown, The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. 2003, Pubmed
Butzner, Inhibition of short-chain fatty acid absorption and Na+ absorption during acute colitis in the rabbit. 1994, Pubmed
Bäckhed, Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. 2007, Pubmed
Bäckhed, The gut microbiota as an environmental factor that regulates fat storage. 2004, Pubmed
Bäckhed, Host-bacterial mutualism in the human intestine. 2005, Pubmed
Canani, Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. 2011, Pubmed
Cani, Gut microflora as a target for energy and metabolic homeostasis. 2007, Pubmed
Chen, NOD-like receptors: role in innate immunity and inflammatory disease. 2009, Pubmed
Cohn, Asthma: mechanisms of disease persistence and progression. 2004, Pubmed
Cresci, Colonic gene expression in conventional and germ-free mice with a focus on the butyrate receptor GPR109A and the butyrate transporter SLC5A8. 2010, Pubmed
De Vadder, Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. 2014, Pubmed
Delzenne, Interaction between obesity and the gut microbiota: relevance in nutrition. 2011, Pubmed
Dominguez-Bello, Development of the human gastrointestinal microbiota and insights from high-throughput sequencing. 2011, Pubmed
Dupaul-Chicoine, Control of intestinal homeostasis, colitis, and colitis-associated colorectal cancer by the inflammatory caspases. 2010, Pubmed
Eckburg, Diversity of the human intestinal microbial flora. 2005, Pubmed
Elinav, Regulation of the antimicrobial response by NLR proteins. 2011, Pubmed
Elinav, NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. 2011, Pubmed
Fanaro, Intestinal microflora in early infancy: composition and development. 2003, Pubmed
Feleszko, Probiotic-induced suppression of allergic sensitization and airway inflammation is associated with an increase of T regulatory-dependent mechanisms in a murine model of asthma. 2007, Pubmed
Field, Intestinal electrolyte transport and diarrheal disease (2). 1989, Pubmed
Forsythe, Probiotics and lung immune responses. 2014, Pubmed
Frank, Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. 2007, Pubmed
Frost, The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. 2014, Pubmed
Fukuda, Bifidobacteria can protect from enteropathogenic infection through production of acetate. 2011, Pubmed
Furusawa, Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. 2013, Pubmed
Ge, Activation of G protein-coupled receptor 43 in adipocytes leads to inhibition of lipolysis and suppression of plasma free fatty acids. 2008, Pubmed
Ghoshal, The gut microbiota and irritable bowel syndrome: friend or foe? 2012, Pubmed
Gupta, SLC5A8 (SMCT1)-mediated transport of butyrate forms the basis for the tumor suppressive function of the transporter. 2006, Pubmed
Hamer, Review article: the role of butyrate on colonic function. 2008, Pubmed
Haslam, Obesity. 2005, Pubmed
Hawrelak, The causes of intestinal dysbiosis: a review. 2004, Pubmed
Herbst, Dysregulation of allergic airway inflammation in the absence of microbial colonization. 2011, Pubmed
Hill, Commensal bacteria-derived signals regulate basophil hematopoiesis and allergic inflammation. 2012, Pubmed
Hirota, NLRP3 inflammasome plays a key role in the regulation of intestinal homeostasis. 2011, Pubmed
Holmes, Gut microbiota composition and activity in relation to host metabolic phenotype and disease risk. 2012, Pubmed
Holtug, Short chain fatty acids in inflammatory bowel disease. The effect of bacterial fermentation of blood. 1988, Pubmed
Hotte, Patients with inflammatory bowel disease exhibit dysregulated responses to microbial DNA. 2012, Pubmed
Hyman, Microbes on the human vaginal epithelium. 2005, Pubmed
Jobin, The I kappa B/NF-kappa B system: a key determinant of mucosalinflammation and protection. 2000, Pubmed
Kalliomäki, Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing. 2001, Pubmed
Kalliomäki, Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. 2001, Pubmed
Kang, An antibiotic-responsive mouse model of fulminant ulcerative colitis. 2008, Pubmed
Kaser, Inflammatory bowel disease. 2010, Pubmed
Kelsen, The gut microbiota, environment and diseases of modern society. 2012, Pubmed
Kim, Short-chain fatty acids activate GPR41 and GPR43 on intestinal epithelial cells to promote inflammatory responses in mice. 2013, Pubmed
Koenig, Succession of microbial consortia in the developing infant gut microbiome. 2011, Pubmed
Le Poul, Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. 2003, Pubmed
Lepage, Dysbiosis in inflammatory bowel disease: a role for bacteriophages? 2008, Pubmed
Lissner, The multifaceted role of the inflammasome in inflammatory bowel diseases. 2011, Pubmed
Lührs, Butyrate inhibits NF-kappaB activation in lamina propria macrophages of patients with ulcerative colitis. 2002, Pubmed
Maslowski, Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. 2009, Pubmed
Masoli, The global burden of asthma: executive summary of the GINA Dissemination Committee report. 2004, Pubmed
Mow, Association of antibody responses to microbial antigens and complications of small bowel Crohn's disease. 2004, Pubmed
Mutlu, Intestinal dysbiosis: a possible mechanism of alcohol-induced endotoxemia and alcoholic steatohepatitis in rats. 2009, Pubmed
Noverr, The 'microflora hypothesis' of allergic diseases. 2005, Pubmed
O'Hara, The gut flora as a forgotten organ. 2006, Pubmed
Ober, Gene-environment interactions in human disease: nuisance or opportunity? 2011, Pubmed
Olszak, Microbial exposure during early life has persistent effects on natural killer T cell function. 2012, Pubmed
Oyama, Antibiotic use during infancy promotes a shift in the T(H)1/T(H)2 balance toward T(H)2-dominant immunity in mice. 2001, Pubmed
Pagnini, Probiotics promote gut health through stimulation of epithelial innate immunity. 2010, Pubmed
Penders, Factors influencing the composition of the intestinal microbiota in early infancy. 2006, Pubmed
Qin, A human gut microbial gene catalogue established by metagenomic sequencing. 2010, Pubmed
Robertson, Nod-like receptors in intestinal host defense: controlling pathogens, the microbiota, or both? 2013, Pubmed
Round, Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. 2010, Pubmed
Russell, Early life antibiotic-driven changes in microbiota enhance susceptibility to allergic asthma. 2012, Pubmed
Samuel, Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. 2008, Pubmed
Scheppach, Fecal short-chain fatty acid (SCFA) analysis by capillary gas-liquid chromatography. 1987, Pubmed
Schroder, The inflammasomes. 2010, Pubmed
Segain, Butyrate inhibits inflammatory responses through NFkappaB inhibition: implications for Crohn's disease. 2000, Pubmed
Seljeset, Receptor-specific regulation of ERK1/2 activation by members of the "free fatty acid receptor" family. 2012, Pubmed
Sharma, Molecular modulation of intestinal epithelial barrier: contribution of microbiota. 2010, Pubmed
Singh, Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. 2014, Pubmed
Smith, The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. 2013, Pubmed
Strachan, Hay fever, hygiene, and household size. 1989, Pubmed
Subramanian, Bacteria in the pathogenesis of inflammatory bowel disease. 2006, Pubmed
Swidsinski, Mucosal flora in Crohn's disease and ulcerative colitis - an overview. 2009, Pubmed
Swinburn, The global obesity pandemic: shaped by global drivers and local environments. 2011, Pubmed
Thangaraju, GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. 2009, Pubmed
Thangaraju, Transport by SLC5A8 with subsequent inhibition of histone deacetylase 1 (HDAC1) and HDAC3 underlies the antitumor activity of 3-bromopyruvate. 2009, Pubmed
Tilg, Obesity and the microbiota. 2009, Pubmed
Topping, Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. 2001, Pubmed
Trompette, Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. 2014, Pubmed
Vercelli, Gene-environment interactions: the road less traveled by in asthma genetics. 2009, Pubmed
Vercelli, Gene-environment interactions in asthma and allergy: the end of the beginning? 2010, Pubmed
Videla, Role of intestinal microflora in chronic inflammation and ulceration of the rat colon. 1994, Pubmed
Vijay-Kumar, Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. 2010, Pubmed
Vinolo, Suppressive effect of short-chain fatty acids on production of proinflammatory mediators by neutrophils. 2011, Pubmed
Vinolo, Regulation of inflammation by short chain fatty acids. 2011, Pubmed
Vinolo, G-protein-coupled receptors as fat sensors. 2012, Pubmed
Vinolo, Effects of short chain fatty acids on effector mechanisms of neutrophils. 2009, Pubmed
Wells, Epithelial crosstalk at the microbiota-mucosal interface. 2011, Pubmed
Weston, Effects of probiotics on atopic dermatitis: a randomised controlled trial. 2005, Pubmed
Wickens, Antibiotic use in early childhood and the development of asthma. 1999, Pubmed
Wills-Karp, The germless theory of allergic disease: revisiting the hygiene hypothesis. 2001, Pubmed
Xu, Evolution of symbiotic bacteria in the distal human intestine. 2007, Pubmed
Yan, Enteric dysbiosis associated with a mouse model of alcoholic liver disease. 2011, Pubmed
Yatsunenko, Human gut microbiome viewed across age and geography. 2012, Pubmed
Zaki, The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis. 2010, Pubmed
van Nimwegen, Mode and place of delivery, gastrointestinal microbiota, and their influence on asthma and atopy. 2011, Pubmed
von Mutius, Farm living: effects on childhood asthma and allergy. 2010, Pubmed