1.El Aidy S, van den Bogert B & Kleerebezem M (2015) The small intestine microbiota, nutritional modulation and relevance for health. Curr Opin Biotechnol 32, 14–20.
2.van der Schaar PJ, Dijksman JF, Broekhuizen-de Gast H, et al. (2013) A novel ingestible electronic drug delivery and monitoring device. Gastrointest Endosc 78, 520–528.
3.Rajilic-Stojanovic M, Heilig HG, Molenaar D, et al. (2009) Development and application of the human intestinal tract chip, a phylogenetic microarray: analysis of universally conserved phylotypes in the abundant microbiota of young and elderly adults. Environ Microbiol 11, 1736–1751.
4.Booijink CC, El-Aidy S, Rajilic-Stojanovic M, et al. (2010) High temporal and inter-individual variation detected in the human ileal microbiota. Environ Microbiol 12, 3213–3227.
5.van den Bogert B, de Vos WM, Zoetendal EG, et al. (2011) Microarray analysis and barcoded pyrosequencing provide consistent microbial profiles depending on the source of human intestinal samples. Appl Environ Microbiol 77, 2071–2080.
6.Zoetendal EG, Raes J, van den Bogert B, et al. (2012) The human small intestinal microbiota is driven by rapid uptake and conversion of simple carbohydrates. ISME J 6, 1415–1426.
7.van den Bogert B, Erkus O, Boekhorst J, et al. (2013) Diversity of human small intestinal Streptococcus and Veillonella populations. FEMS Microbiol Ecol 85, 376–388.
8.van Baarlen P, Troost F, van der Meer C, et al. (2011) Human mucosal in vivo transcriptome responses to three lactobacilli indicate how probiotics may modulate human cellular pathways. Proc Natl Acad Sci U S A 108, Suppl. 1, 4562–4569.
9.van Baarlen P, Troost FJ, van Hemert S, et al. (2009) Differential NF-kappaB pathways induction by Lactobacillus plantarum in the duodenum of healthy humans correlating with immune tolerance. Proc Natl Acad Sci U S A 106, 2371–2376.
10.Yan F, Cao H, Cover TL, et al. (2007) Soluble proteins produced by probiotic bacteria regulate intestinal epithelial cell survival and growth. Gastroenterology 132, 562–575.
11.Lamb J (2007) The connectivity map: a new tool for biomedical research. Nat Rev Cancer 7, 54–60.
12.Bron PA, van Baarlen P & Kleerebezem M (2012) Emerging molecular insights into the interaction between probiotics and the host intestinal mucosa. Nat Rev Microbiol 10, 66–78.
13.Hedin CR, Stagg AJ, Whelan K, et al. (2012) Family studies in Crohn’s disease: new horizons in understanding disease pathogenesis, risk and prevention. Gut 61, 311–318.
14.Frank DN, St Amand AL, Feldman RA, et al. (2007) Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A 104, 13780–13785.
15.Lepage P, Hasler R, Spehlmann ME, et al. (2011) Twin study indicates loss of interaction between microbiota and mucosa of patients with ulcerative colitis. Gastroenterology 141, 227–236.
16.Renz H, von Mutius E, Brandtzaeg P, et al. (2011) Gene-environment interactions in chronic inflammatory disease. Nat Immunol 12, 273–277.
17.Hilsden RJ, Verhoef MJ, Rasmussen H, et al. (2011) Use of complementary and alternative medicine by patients with inflammatory bowel disease. Inflamm Bowel Dis 17, 655–662.
18.Fernandez-Banares F, Hinojosa J, Sanchez-Lombrana JL, et al. (1999) Randomized clinical trial of Plantago ovata seeds (dietary fiber) as compared with mesalamine in maintaining remission in ulcerative colitis. Spanish Group for the Study of Crohn’s Disease and Ulcerative Colitis (GETECCU). Am J Gastroenterol 94, 427–433.
19.Fujimori S, Tatsuguchi A, Gudis K, et al. (2007) High dose probiotic and prebiotic cotherapy for remission induction of active Crohn’s disease. J Gastroenterol Hepatol 22, 1199–1204.
20.Langhorst J, Wulfert H, Lauche R, et al. (2015) Systematic review of complementary and alternative medicine treatments in inflammatory bowel diseases. J Crohns Colitis 9, 86–106.
21.Dignass A, Preiss JC, Aust DE, et al. (2011) [Updated German guideline on diagnosis and treatment of ulcerative colitis, 2011]. Z Gastroenterol 49, 1276–1341.
22.Storr M, Devlin S, Kaplan GG, et al. (2014) Cannabis use provides symptom relief in patients with inflammatory bowel disease but is associated with worse disease prognosis in patients with Crohn’s disease. Inflamm Bowel Dis 20, 472–480.
23.Joos S, Wildau N, Kohnen R, et al. (2006) Acupuncture and moxibustion in the treatment of ulcerative colitis: a randomized controlled study. Scand J Gastroenterol 41, 1056–1063.
24.Rogler G & Vavricka S (2015) Exposome in IBD: recent insights in environmental factors that influence the onset and course of IBD. Inflamm Bowel Dis 21, 400–408.
25.Clarke SF, Murphy EF, O’Sullivan O, et al. (2014) Exercise and associated dietary extremes impact on gut microbial diversity. Gut 63, 1913–1920.
26.Cosnes J (2010) Smoking, physical activity, nutrition and lifestyle: environmental factors and their impact on IBD. Dig Dis 28, 411–417.
27.Levenstein S, Prantera C, Varvo V, et al. (2000) Stress and exacerbation in ulcerative colitis: a prospective study of patients enrolled in remission. Am J Gastroenterol 95, 1213–1220.
28.Bernstein CN, Singh S, Graff LA, et al. (2010) A prospective population-based study of triggers of symptomatic flares in IBD. Am J Gastroenterol 105, 1994–2002.
29.Jedel S, Hoffman A, Merriman P, et al. (2014) A randomized controlled trial of mindfulness-based stress reduction to prevent flare-up in patients with inactive ulcerative colitis. Digestion 89, 142–155.
30.Berrill JW, Sadlier M, Hood K, et al. (2014) Mindfulness-based therapy for inflammatory bowel disease patients with functional abdominal symptoms or high perceived stress levels. J Crohns Colitis 8, 945–955.
31.Bailey MT, Dowd SE, Galley JD, et al. (2011) Exposure to a social stressor alters the structure of the intestinal microbiota: implications for stressor-induced immunomodulation. Brain Behav Immun 25, 397–407.
32.van Nood E, Vrieze A, Nieuwdorp M, et al. (2013) Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med 368, 407–415.
33.Kao D, Hotte N, Gillevet P, et al. (2014) Fecal microbiota transplantation inducing remission in Crohn’s colitis and the associated changes in fecal microbial profile. J Clin Gastroenterol 48, 625–628.
34.Kump PK, Grochenig HP, Lackner S, et al. (2013) Alteration of intestinal dysbiosis by fecal microbiota transplantation does not induce remission in patients with chronic active ulcerative colitis. Inflamm Bowel Dis 19, 2155–2165.
35.Moayyedi P, Surette MG, Kim PT, et al. (2015) Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized, controlled trial. Gastroenterology 149, 102–109.
36.Rossen NG, Fuentes S, van der Spek MJ, et al. (2015) Findings from a randomized controlled trial of fecal transplantation for patients with ulcerative colitis. Gastroenterology 149, 110–118.
37.Jones J & Hunter D (1995) Consensus methods for medical and health services research. BMJ 311, 376–380.
38.Guyatt GH, Oxman AD, Schunemann HJ, et al. (2011) GRADE guidelines: a new series of articles in the Journal of Clinical Epidemiology. J Clin Epidemiol 64, 380–382.
39.O’Mahony L, McCarthy J, Kelly P, et al. (2005) Lactobacillus and Bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology 128, 541–551.
40.Whorwell PJ, Altringer L, Morel J, et al. (2006) Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome. Am J Gastroenterol 101, 1581–1590.
41.McFarland LV & Dublin S (2008) Meta-analysis of probiotics for the treatment of irritable bowel syndrome. World J Gastroenterol 14, 2650–2661.
42.Ford AC, Quigley EM, Lacy BE, et al. (2014) Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: systematic review and meta-analysis. Am J Gastroenterol 109, 1547–1561 quiz 1546, 1562.
43.Chang L, Lembo A & Sultan S (2014) American Gastroenterological Association Institute Technical Review on the pharmacological management of irritable bowel syndrome. Gastroenterology 147, 1149–1172.
45.Layer P, Andresen V, Pehl C, et al. (2011) [Irritable bowel syndrome: German consensus guidelines on definition, pathophysiology and management]. Z Gastroenterol 49, 237–293.
46.Szajewska H, Guarino A, Hojsak I, et al. (2014) Use of probiotics for management of acute gastroenteritis: a position paper by the ESPGHAN Working Group for Probiotics and Prebiotics. J Pediatr Gastroenterol Nutr 58, 531–539.
47.Saavedra JM, Bauman NA, Oung I, et al. (1994) Feeding of Bifidobacterium bifidum and Streptococcus thermophilus to infants in hospital for prevention of diarrhoea and shedding of rotavirus. Lancet 344, 1046–1049.
48.Szajewska H, Wanke M & Patro B (2011) Meta-analysis: the effects of Lactobacillus rhamnosus GG supplementation for the prevention of healthcare-associated diarrhoea in children. Aliment Pharmacol Ther 34, 1079–1087.
49.Hojsak I, Tokic Pivac V, Mocic Pavic A, et al. (2015) Bifidobacterium animalis subsp. lactis fails to prevent common infections in hospitalized children: a randomized, double-blind, placebo-controlled study. Am J Clin Nutr 101, 680–684.
50.Hempel S, Newberry SJ, Maher AR, et al. (2012) Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis. JAMA 307, 1959–1969.
51.AlFaleh K & Anabrees J (2014) Probiotics for prevention of necrotizing enterocolitis in preterm infants. Evid Based Child Health 9, 584–671.
52.Chau K, Lau E, Greenberg S, et al. (2015) Probiotics for infantile colic: a randomized, double-blind, placebo-controlled trial investigating Lactobacillus reuteri DSM 17938. J Pediatr 166, 74–78.
53.Mi GL, Zhao L, Qiao DD, et al. (2015) Effectiveness of Lactobacillus reuteri in infantile colic and colicky induced maternal depression: a prospective single blind randomized trial. Antonie Van Leeuwenhoek 107, 1547–1553.
54.Sung V, Hiscock H, Tang ML, et al. (2014) Treating infant colic with the probiotic Lactobacillus reuteri: double blind, placebo controlled randomised trial. BMJ 348, g2107.
55.Urbanska M & Szajewska H (2014) The efficacy of Lactobacillus reuteri DSM 17938 in infants and children: a review of the current evidence. Eur J Pediatr 173, 1327–1337.
56.Indrio F, Di Mauro A, Riezzo G, et al. (2014) Prophylactic use of a probiotic in the prevention of colic, regurgitation, and functional constipation: a randomized clinical trial. JAMA Pediatr 168, 228–233.
57.Fiocchi A, Pawankar R, Cuello-Garcia C, et al. (2015) World Allergy Organization-McMaster University guidelines for allergic disease prevention (GLAD-P): probiotics. World Allergy Organ J 8, 4.
58.Aljada A, Mohanty P, Ghanim H, et al. (2004) Increase in intranuclear nuclear factor kappaB and decrease in inhibitor kappaB in mononuclear cells after a mixed meal: evidence for a proinflammatory effect. Am J Clin Nutr 79, 682–690.
59.Nappo F, Esposito K, Cioffi M, et al. (2002) Postprandial endothelial activation in healthy subjects and in type 2 diabetic patients: role of fat and carbohydrate meals. J Am Coll Cardiol 39, 1145–1150.
60.Miglio C, Peluso I, Raguzzini A, et al. (2013) Antioxidant and inflammatory response following high-fat meal consumption in overweight subjects. Eur J Nutr 52, 1107–1114.
61.Peluso I, Raguzzini A, Villano DV, et al. (2012) High fat meal increase of IL-17 is prevented by ingestion of fruit juice drink in healthy overweight subjects. Curr Pharm Des 18, 85–90.
62.Miglio C, Peluso I, Raguzzini A, et al. (2014) Fruit juice drinks prevent endogenous antioxidant response to high-fat meal ingestion. Br J Nutr 111, 294–300.
63.Peluso I, Miglio C, Morabito G, et al. (2015) Flavonoids and immune function in human: a systematic review. Crit Rev Food Sci Nutr 55, 383–395.
64.Serafini M, Bugianesi R, Maiani G, et al. (2003) Plasma antioxidants from chocolate. Nature 424, 1013.
65.Marin L, Miguelez EM, Villar CJ, et al. (2015) Bioavailability of dietary polyphenols and gut microbiota metabolism: antimicrobial properties. Biomed Res Int 2015, 905215.
66.Chen Z, Zheng S, Li L, et al. (2014) Metabolism of flavonoids in human: a comprehensive review. Curr Drug Metab 15, 48–61.
67.Nagpal R, Yadav H & Marotta F (2014) Gut microbiota: the next-gen frontier in preventive and therapeutic medicine? Front Med (Lausanne) 1, 15.
68.Ishii Y, Sugimoto S, Izawa N, et al. (2014) Oral administration of Bifidobacterium breve attenuates UV-induced barrier perturbation and oxidative stress in hairless mice skin. Arch Dermatol Res 306, 467–473.
69.Wang AN, Yi XW, Yu HF, et al. (2009) Free radical scavenging activity of Lactobacillus fermentum in vitro and its antioxidative effect on growing-finishing pigs. J Appl Microbiol 107, 1140–1148.
70.Kaushal D & Kansal VK (2014) Dahi containing Lactobacillus acidophilus and Bifidobacterium bifidum improves phagocytic potential of macrophages in aged mice. J Food Sci Technol 51, 1147–1153.
71.Kumar RS, Kanmani P, Yuvaraj N, et al. (2012) Lactobacillus plantarum AS1 isolated from south Indian fermented food Kallappam suppress 1,2-dimethyl hydrazine (DMH)-induced colorectal cancer in male Wistar rats. Appl Biochem Biotechnol 166, 620–631.
72.Sengul N, Isik S, Aslim B, et al. (2011) The effect of exopolysaccharide-producing probiotic strains on gut oxidative damage in experimental colitis. Dig Dis Sci 56, 707–714.
73.Ejtahed HS, Mohtadi-Nia J, Homayouni-Rad A, et al. (2012) Probiotic yogurt improves antioxidant status in type 2 diabetic patients. Nutrition 28, 539–543.
74.Tilg H & Moschen AR (2014) Microbiota and diabetes: an evolving relationship. Gut 63, 1513–1521.
75.Le Chatelier E, Nielsen T, Qin J, et al. (2013) Richness of human gut microbiome correlates with metabolic markers. Nature 500, 541–546.
76.Cani PD, Osto M, Geurts L, et al. (2012) Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity. Gut Microbes 3, 279–288.
77.Everard A, Belzer C, Geurts L, et al. (2013) Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci U S A 110, 9066–9071.
78.Druart C, Bindels LB, Schmaltz R, et al. (2015) Ability of the gut microbiota to produce PUFA-derived bacterial metabolites: proof of concept in germ-free versus conventionalized mice. Mol Nutr Food Res 59, 1603–1613.
79.Kang JH, Yun SI & Park HO (2010) Effects of Lactobacillus gasseri BNR17 on body weight and adipose tissue mass in diet-induced overweight rats. J Microbiol 48, 712–714.
80.Karlsson CL, Molin G, Fak F, et al. (2011) Effects on weight gain and gut microbiota in rats given bacterial supplements and a high-energy-dense diet from fetal life through to 6 months of age. Br J Nutr 106, 887–895.
81.Esposito E, Iacono A, Bianco G, et al. (2009) Probiotics reduce the inflammatory response induced by a high-fat diet in the liver of young rats. J Nutr 139, 905–911.
82.Chen J, Wang R, Li XF, et al. (2012) Bifidobacterium adolescentis supplementation ameliorates visceral fat accumulation and insulin sensitivity in an experimental model of the metabolic syndrome. Br J Nutr 107, 1429–1434.
83.Wang J, Tang H, Zhang C, et al. (2015) Modulation of gut microbiota during probiotic-mediated attenuation of metabolic syndrome in high fat diet-fed mice. ISME J 9, 1–15.
84.Kadooka Y, Sato M, Ogawa A, et al. (2013) Effect of Lactobacillus gasseri SBT2055 in fermented milk on abdominal adiposity in adults in a randomised controlled trial. Br J Nutr 110, 1696–1703.
85.Woodard GA, Encarnacion B, Downey JR, et al. (2009) Probiotics improve outcomes after Roux-en-Y gastric bypass surgery: a prospective randomized trial. J Gastrointest Surg 13, 1198–1204.
86.Druart C, Alligier M, Salazar N, et al. (2014) Modulation of the gut microbiota by nutrients with prebiotic and probiotic properties. Adv Nutr 5, 624S–633S.
87.Hulston CJ, Churnside AA & Venables MC (2015) Probiotic supplementation prevents high-fat, overfeeding-induced insulin resistance in human subjects. Br J Nutr 113, 596–602.
88.Weng H, Endo K, Li J, et al. (2015) Induction of peroxisomes by butyrate-producing probiotics. PLOS ONE 10, e0117851.
89.Coakley M, Ross RP, Nordgren M, et al. (2003) Conjugated linoleic acid biosynthesis by human-derived Bifidobacterium species. J Appl Microbiol 94, 138–145.
90.Everard A, Lazarevic V, Derrien M, et al. (2011) Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice. Diabetes 60, 2775–2786.
91.Everard A, Lazarevic V, Gaia N, et al. (2014) Microbiome of prebiotic-treated mice reveals novel targets involved in host response during obesity. ISME J 8, 2116–2130.
92.Geurts L, Neyrinck AM, Delzenne NM, et al. (2014) Gut microbiota controls adipose tissue expansion, gut barrier and glucose metabolism: novel insights into molecular targets and interventions using prebiotics. Benef Microbes 5, 3–17.
93.Kellow NJ, Coughlan MT & Reid CM (2014) Metabolic benefits of dietary prebiotics in human subjects: a systematic review of randomised controlled trials. Br J Nutr 111, 1147–1161.
94.Dewulf EM, Cani PD, Claus SP, et al. (2013) Insight into the prebiotic concept: lessons from an exploratory, double blind intervention study with inulin-type fructans in obese women. Gut 62, 1112–1121.
95.Salazar N, Dewulf EM, Neyrinck AM, et al. (2015) Inulin-type fructans modulate intestinal Bifidobacterium species populations and decrease fecal short-chain fatty acids in obese women. Clin Nutr 34, 501–507.
96.Druart C, Dewulf EM, Cani PD, et al. (2014) Gut microbial metabolites of polyunsaturated fatty acids correlate with specific fecal bacteria and serum markers of metabolic syndrome in obese women. Lipids 49, 397–402.
97.Larsen N, Vogensen FK, van den Berg FW, et al. (2010) Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS ONE 5, e9085.
98.Cani PD, Possemiers S, Van de Wiele T, et al. (2009) Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut 58, 1091–1103.
99.El Aidy SE, Dinan TG & Cryan JF (2015) Gut microbiota: the conductor in the orchestra of immune-neuroendocrine communication. Clin Ther 37, 954–967.
100.Stilling RM, Bordenstein SR, Dinan TG, et al. (2014) Friends with social benefits: host-microbe interactions as a driver of brain evolution and development? Front Cell Infect Microbiol 4, 147.
101.Cryan JF & Dinan TG (2012) Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci 13, 701–712.
102.O’Mahony SM, Marchesi JR, Scully P, et al. (2009) Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses. Biol Psychiatry 65, 263–267.
103.O’Malley D, Julio-Pieper M, Gibney SM, et al. (2010) Distinct alterations in colonic morphology and physiology in two rat models of enhanced stress-induced anxiety and depression-like behaviour. Stress 13, 114–122.
104.Borre YE, O’Keeffe GW, Clarke G, et al. (2014) Microbiota and neurodevelopmental windows: implications for brain disorders. Trends Mol Med 20, 509–518.
105.Wall R, Cryan JF, Ross RP, et al. (2014) Bacterial neuroactive compounds produced by psychobiotics. Adv Exp Med Biol 817, 221–239.
106.Sudo N, Chida Y, Aiba Y, et al. (2004) Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J Physiol 558, 263–275.
107.Diaz Heijtz R, Wang S, Anuar F, et al. (2011) Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci U S A 108, 3047–3052.
108.Neufeld KM, Kang N, Bienenstock J, et al. (2011) Reduced anxiety-like behavior and central neurochemical change in germ-free mice. Neurogastroenterol Motil 23, 255–264.
109.Clarke G, Grenham S, Scully P, et al. (2013) The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol Psychiatry 18, 666–673.
110.Ogbonnaya ES, Clarke G, Shanahan F, et al. (2015) Adult hippocampal neurogenesis is regulated by the microbiome. Biol Psychiatry 78, e7–e9.
111.Braniste V, Al-Asmakh M, Kowal C, et al. (2014) The gut microbiota influences blood-brain barrier permeability in mice. Sci Transl Med 6, 263ra158.
112.Stilling RM, Dinan TG & Cryan JF (2014) Microbial genes, brain & behaviour – epigenetic regulation of the gut-brain axis. Genes Brain Behav 13, 69–86.
113.Bravo JA, Forsythe P, Chew MV, et al. (2011) Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A 108, 16050–16055.
114.Savignac HM, Tramullas M, Kiely B, et al. (2015) Bifidobacteria modulate cognitive processes in an anxious mouse strain. Behav Brain Res 287, 59–72.
115.Desbonnet L, Clarke G, Shanahan F, et al. (2014) Microbiota is essential for social development in the mouse. Mol Psychiatry 19, 146–148.
116.de Theije CG, Wopereis H, Ramadan M, et al. (2014) Altered gut microbiota and activity in a murine model of autism spectrum disorders. Brain Behav Immun 37, 197–206.
117.Hsiao EY, McBride SW, Hsien S, et al. (2013) Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155, 1451–1463.
118.Gilbert JA, Krajmalnik-Brown R, Porazinska DL, et al. (2013) Toward effective probiotics for autism and other neurodevelopmental disorders. Cell 155, 1446–1448.
119.Collins SM, Kassam Z & Bercik P (2013) The adoptive transfer of behavioral phenotype via the intestinal microbiota: experimental evidence and clinical implications. Curr Opin Microbiol 16, 240–245.
120.Bruce-Keller AJ, Salbaum JM, Luo M, et al. (2015) Obese-type gut microbiota induce neurobehavioral changes in the absence of obesity. Biol Psychiatry 77, 607–615.
121.O’Mahony SM, Felice VD, Nally K, et al. (2014) Disturbance of the gut microbiota in early-life selectively affects visceral pain in adulthood without impacting cognitive or anxiety-related behaviors in male rats. Neuroscience 277, 885–901.
122.Jeffery IB, O’Toole PW, Ohman L, et al. (2012) An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota. Gut 61, 997–1006.
123.McKernan DP, Fitzgerald P, Dinan TG, et al. (2010) The probiotic Bifidobacterium infantis 35624 displays visceral antinociceptive effects in the rat. Neurogastroenterol Motil 22, 1029–1035.
124.Clarke G, Cryan JF, Dinan TG, et al. (2012) Review article: probiotics for the treatment of irritable bowel syndrome-focus on lactic acid bacteria. Aliment Pharmacol Ther 35, 403–413.
125.Kennedy PJ, Clarke G, O’Neill A, et al. (2014) Cognitive performance in irritable bowel syndrome: evidence of a stress-related impairment in visuospatial memory. Psychol Med 44, 1553–1566.
126.Dinan TG, Stanton C & Cryan JF (2013) Psychobiotics: a novel class of psychotropic. Biol Psychiatry 74, 720–726.
127.Phillips JGP (1910) The treatment of melancholia by the lactic acid bacillus. J Mental Sci 56, 422–431.
128.Benton D, Williams C & Brown A (2007) Impact of consuming a milk drink containing a probiotic on mood and cognition. Eur J Clin Nutr 61, 355–361.
129.Rao AV, Bested AC, Beaulne TM, et al. (2009) A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathog 1, 6.
130.Steenbergen L, Sellaro R, van Hemert S, et al. (2015) A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain Behav Immun 48, 258–264.
131.Mohammadi AA, Jazayeri S, Khosravi-Darani K, et al. (2015) The effects of probiotics on mental health and hypothalamic-pituitary-adrenal axis: a randomized, double-blind, placebo-controlled trial in petrochemical workers. Nutr Neurosci (Epublication ahead of print version 16 April 2015).
132.Center MM, Jemal A, Lortet-Tieulent J, et al. (2012) International variation in prostate cancer incidence and mortality rates. Eur Urol 61, 1079–1092.
133.Kolonel LN, Altshuler D & Henderson BE (2004) The multiethnic cohort study: exploring genes, lifestyle and cancer risk. Nat Rev Cancer 4, 519–527.
134.Cuzick J, Thorat MA, Andriole G, et al. (2014) Prevention and early detection of prostate cancer. Lancet Oncol 15, e484–e492.
135.Lacy JM & Kyprianou N (2014) A tale of two trials: the impact of 5alpha-reductase inhibition on prostate cancer (review). Oncol Lett 8, 1391–1396.
136.Hebert JR, Hurley TG, Olendzki BC, et al. (1998) Nutritional and socioeconomic factors in relation to prostate cancer mortality: a cross-national study. J Natl Cancer Inst 90, 1637–1647.
137.Yan L & Spitznagel EL (2009) Soy consumption and prostate cancer risk in men: a revisit of a meta-analysis. Am J Clin Nutr 89, 1155–1163.
138.Mahmoud AM, Yang W & Bosland MC (2014) Soy isoflavones and prostate cancer: a review of molecular mechanisms. J Steroid Biochem Mol Biol 140, 116–132.
139.Lund TD, Munson DJ, Haldy ME, et al. (2004) Equol is a novel anti-androgen that inhibits prostate growth and hormone feedback. Biol Reprod 70, 1188–1195.
140.Rafii F (2015) The role of colonic bacteria in the metabolism of the natural isoflavone daidzein to equol. Metabolites 5, 56–73.
141.Tanaka M, Fujimoto K, Chihara Y, et al. (2009) Isoflavone supplements stimulated the production of serum equol and decreased the serum dihydrotestosterone levels in healthy male volunteers. Prostate Cancer Prostatic Dis 12, 247–252.
142.Sugiyama Y, Masumori N, Fukuta F, et al. (2013) Influence of isoflavone intake and equol-producing intestinal flora on prostate cancer risk. Asian Pac J Cancer Prev 14, 1–4.
143.Fujimoto K, Tanaka M, Hirao Y, et al. (2008) Age-stratified serum levels of isoflavones and proportion of equol producers in Japanese and Korean healthy men. Prostate Cancer Prostatic Dis 11, 252–257.
144.Miyanaga N, Akaza H, Hinotsu S, et al. (2012) Prostate cancer chemoprevention study: an investigative randomized control study using purified isoflavones in men with rising prostate-specific antigen. Cancer Sci 103, 125–130.
145.Tsuji H, Moriyama K, Nomoto K, et al. (2012) Identification of an enzyme system for daidzein-to-equol conversion in Slackia sp. strain NATTS. Appl Environ Microbiol 78, 1228–1236.
146.Akaza H (2012) Prostate cancer chemoprevention by soy isoflavones: role of intestinal bacteria as the ‘second human genome’. Cancer Sci 103, 969–975.
147.Wong S, Derry F, Jamous A, et al. (2014) Is undernutrition risk associated with an adverse clinical outcome in spinal cord-injured patients admitted to a spinal centre? Eur J Clin Nutr 68, 125–130.
148.Issa I & Moucari R (2014) Probiotics for antibiotic-associated diarrhea: do we have a verdict? World J Gastroenterol 20, 17788–17795.
149.Wong S, Jamous A, O’Driscoll J, et al. (2014) A Lactobacillus casei Shirota probiotic drink reduces antibiotic-associated diarrhoea in patients with spinal cord injuries: a randomised controlled trial. Br J Nutr 111, 672–678.
150.Brenchley JM, Price DA, Schacker TW, et al. (2006) Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med 12, 1365–1371.
151.Cunningham-Rundles S, Ahrne S, Johann-Liang R, et al. (2011) Effect of probiotic bacteria on microbial host defense, growth, and immune function in human immunodeficiency virus type-1 infection. Nutrients 3, 1042–1070.
152.Dong H, Rowland I, Thomas LV, et al. (2013) Immunomodulatory effects of a probiotic drink containing Lactobacillus casei Shirota in healthy older volunteers. Eur J Nutr 52, 1853–1863.
153.Falasca K, Vecchiet J, Ucciferri C, et al. (2015) Effect of probiotic supplement on cytokine levels in HIV-infected individuals: A preliminary study. Nutrients 7(1), 8335–8347.
154.Miquel S, Martin R, Bridonneau C, et al. (2014) Ecology and metabolism of the beneficial intestinal commensal bacterium Faecalibacterium prausnitzii. Gut Microbes 5, 146–151.
155.Miquel S, Martin R, Rossi O, et al. (2013) Faecalibacterium prausnitzii and human intestinal health. Curr Opin Microbiol 16, 255–261.
156.Qin J, Li R, Raes J, et al. (2010) A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464, 59–65.
157.Sokol H, Pigneur B, Watterlot L, et al. (2008) Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci U S A 105, 16731–16736.
158.Cao Y, Shen J & Ran ZH (2014) Association between Faecalibacterium prausnitzii reduction and inflammatory bowel disease: a meta-analysis and systematic review of the literature. Gastroenterol Res Pract 2014, 872725.
159.Balamurugan R, Rajendiran E, George S, et al. (2008) Real-time polymerase chain reaction quantification of specific butyrate-producing bacteria, Desulfovibrio and Enterococcus faecalis in the feces of patients with colorectal cancer. J Gastroenterol Hepatol 23, 1298–1303.
160.Rajilic-Stojanovic M, Biagi E, Heilig HG, et al. (2011) Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology 141, 1792–1801.
161.Martin R, Chain F, Miquel S, et al. (2014) The commensal bacterium Faecalibacterium prausnitzii is protective in DNBS-induced chronic moderate and severe colitis models. Inflamm Bowel Dis 20, 417–430.
162.Martin R, Miquel S, Chain F, et al. (2015) Faecalibacterium prausnitzii prevents physiological damages in a chronic low-grade inflammation murine model. BMC Microbiol 15, 67.
163.Miquel S, Leclerc M, Martin R, et al. (2015) Identification of metabolic signatures linked to anti-inflammatory effects of Faecalibacterium prausnitzii. MBio 6, e00300–e00315.
164.Read AF, Graham AL & Raberg L (2008) Animal defenses against infectious agents: is damage control more important than pathogen control. PLoS Biol 6, e4.
165.Maloy KJ & Powrie F (2011) Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature 474, 298–306.
166.Round JL & Mazmanian SK (2009) The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol 9, 313–323.
167.Atarashi K, Umesaki Y & Honda K (2011) Microbiotal influence on T cell subset development. Semin Immunol 23, 146–153.
168.Olszak T, An D, Zeissig S, et al. (2012) Microbial exposure during early life has persistent effects on natural killer T cell function. Science 336, 489–493.
169.Noval Rivas M, Burton OT, Wise P, et al. (2013) A microbiota signature associated with experimental food allergy promotes allergic sensitization and anaphylaxis. J Allergy Clin Immunol 131, 201–212.
170.Konieczna P, Akdis CA, Quigley EM, et al. (2012) Portrait of an immunoregulatory Bifidobacterium. Gut Microbes 3, 261–266.
171.O’Mahony C, Scully P, O’Mahony D, et al. (2008) Commensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-kappaB activation. PLoS Pathog 4, e1000112.
172.Groeger D, O’Mahony L, Murphy EF, et al. (2013) Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut. Gut Microbes 4, 325–339.
173.Konieczna P, Groeger D, Ziegler M, et al. (2012) Bifidobacterium infantis 35624 administration induces Foxp3 T regulatory cells in human peripheral blood: potential role for myeloid and plasmacytoid dendritic cells. Gut 61, 354–366.
174.Lyons A, O’Mahony D, O’Brien F, et al. (2010) Bacterial strain-specific induction of Foxp3+ T regulatory cells is protective in murine allergy models. Clin Exp Allergy 40, 811–819.
175.O’Mahony L, Akdis M & Akdis CA (2011) Regulation of the immune response and inflammation by histamine and histamine receptors. J Allergy Clin Immunol 128, 1153–1162.
176.Frei R, Ferstl R, Konieczna P, et al. (2013) Histamine receptor 2 modifies dendritic cell responses to microbial ligands. J Allergy Clin Immunol 132, 194–204.
177.Ferstl R, Frei R, Schiavi E, et al. (2014) Histamine receptor 2 is a key influence in immune responses to intestinal histamine-secreting microbes. J Allergy Clin Immunol 134, 744–746.
178.Roduit C, Frei R, Loss G, et al. (2012) Development of atopic dermatitis according to age of onset and association with early-life exposures. J Allergy Clin Immunol 130, 130–136.
179.Young KT, Davis LM & Dirita VJ (2007) Campylobacter jejuni: molecular biology and pathogenesis. Nat Rev Microbiol 5, 665–679.
180.Bereswill S, Fischer A, Plickert R, et al. (2011) Novel murine infection models provide deep insights into the ‘menage a trois’ of Campylobacter jejuni, microbiota and host innate immunity. PLoS ONE 6, e20953.
181.Heimesaat MM, Plickert R, Fischer A, et al. (2013) Can microbiota transplantation abrogate murine colonization resistance against Campylobacter jejuni? Eur J Microbiol Immunol (Bp) 3, 36–43.
182.Haag LM, Fischer A, Otto B, et al. (2012) Intestinal microbiota shifts towards elevated commensal Escherichia coli loads abrogate colonization resistance against Campylobacter jejuni in mice. PLOS ONE 7, e35988.
183.Heimesaat MM & Bereswill S (2015) Murine infection models for the investigation of Campylobacter jejuni – host interactions and pathogenicity. Berl Munch Tierarztl Wochenschr 128, 98–103.
184.Haag LM, Fischer A, Otto B, et al. (2012) Campylobacter jejuni induces acute enterocolitis in gnotobiotic IL-10-/- mice via toll-like-receptor-2 and -4 signaling. PLOS ONE 7, e40761.
185.Mortensen NP, Kuijf ML, Ang CW, et al. (2009) Sialylation of Campylobacter jejuni lipo-oligosaccharides is associated with severe gastro-enteritis and reactive arthritis. Microbes Infect 11, 988–994.
186.Edwards LA, Nistala K, Mills DC, et al. (2010) Delineation of the innate and adaptive T-cell immune outcome in the human host in response to Campylobacter jejuni infection. PLoS ONE 5, e15398.
187.Kholy KE, Genco RJ & Van Dyke TE (2015) Oral infections and cardiovascular disease. Trends Endocrinol Metab 26, 315–321.
188.Hajishengallis G (2015) Periodontitis: from microbial immune subversion to systemic inflammation. Nat Rev Immunol 15, 30–44.
189.Olsen I (2015) From the acta prize lecture 2014: the periodontal-systemic connection seen from a microbiological standpoint. Acta Odontol Scand 73, 563–568.
190.Niederman R, Buyle-Bodin Y, Lu BY, et al. (1997) Short-chain carboxylic acid concentration in human gingival crevicular fluid. J Dent Res 76, 575–579.
191.Kurita-Ochiai T, Fukushima K & Ochiai K (1995) Volatile fatty acids, metabolic by-products of periodontopathic bacteria, inhibit lymphocyte proliferation and cytokine production. J Dent Res 74, 1367–1373.
192.Yoneda S, Kawarai T, Narisawa N, et al. (2013) Effects of short-chain fatty acids on Actinomyces naeslundii biofilm formation. Mol Oral Microbiol 28, 354–365.
193.Arai T, Ochiai K & Senpuku H (2015) Actinomyces naeslundii GroEL-dependent initial attachment and biofilm formation in a flow cell system. J Microbiol Methods 109, 160–166.
194.Kurita-Ochiai T, Ochiai K & Fukushima K (2000) Butyric-acid-induced apoptosis in murine thymocytes and splenic T- and B-cells occurs in the absence of p53. J Dent Res 79, 1948–1954.
195.Kurita-Ochiai T, Amano S, Fukushima K, et al. (2003) Cellular events involved in butyric acid-induced T cell apoptosis. J Immunol 171, 3576–3584.
196.Kurita-Ochiai T, Seto S & Ochiai K (2004) Role of cell-cell communication in inhibiting butyric acid-induced T-cell apoptosis. Infect Immun 72, 5947–5954.
197.Kurita-Ochiai T, Seto S, Suzuki N, et al. (2008) Butyric acid induces apoptosis in inflamed fibroblasts. J Dent Res 87, 51–55.
198.Cueno ME, Imai K, Tamura M, et al. (2014) Butyric acid-induced rat jugular blood cytosolic oxidative stress is associated with SIRT1 decrease. Cell Stress Chaperones 19, 295–298.
199.Cueno ME, Tamura M & Ochiai K (2015) Middle-aged rats orally supplemented with gel-encapsulated catechin favorably increases blood cytosolic NADPH levels. Phytomedicine 22, 425–430.
200.Imai K, Yamada K, Tamura M, et al. (2012) Reactivation of latent HIV-1 by a wide variety of butyric acid-producing bacteria. Cell Mol Life Sci 69, 2583–2592.
201.Cueno ME, Imai K, Matsukawa N, et al. (2013) Butyric acid retention in gingival tissue induces oxidative stress in jugular blood mitochondria. Cell Stress Chaperones 18, 661–665.
202.Cueno ME, Tamura M, Ohya M, et al. (2014) Similar physiological effects in Porphyromonas gingivalis ATCC 33277 under hemin-excess and hemin-limited concentrations are putatively associated to different hydrogen peroxide function. Anaerobe 28, 178–181.
203.Cornelius C, Koverech G, Crupi R, et al. (2014) Osteoporosis and Alzheimer pathology: role of cellular stress response and hormetic redox signaling in aging and bone remodeling. Front Pharmacol 5, 120.
204.Cueno ME, Kamio N, Seki K, et al. (2015) High butyric acid amounts induce oxidative stress, alter calcium homeostasis, and cause neurite retraction in nerve growth factor-treated PC12 cells. Cell Stress Chaperones 20, 709–713.
205.Shalini S, Dorstyn L, Dawar S, et al. (2015) Old, new and emerging functions of caspases. Cell Death Differ 22, 526–539.
206.Maticic M, Poljak M, Kramar B, et al. (2000) Proviral HIV-1 DNA in gingival crevicular fluid of HIV-1-infected patients in various stages of HIV disease. J Dent Res 79, 1496–1501.
207.Imai K, Ochiai K & Okamoto T (2009) Reactivation of latent HIV-1 infection by the periodontopathic bacterium Porphyromonas gingivalis involves histone modification. J Immunol 182, 3688–3695.
208.Saygun I, Nizam N, Keskiner I, et al. (2011) Salivary infectious agents and periodontal disease status. J Periodontal Res 46, 235–239.
209.Konstantinidis A, Sakellari D, Papa A, et al. (2005) Real-time polymerase chain reaction quantification of Epstein-Barr virus in chronic periodontitis patients. J Periodontal Res 40, 294–298.
210.Imai K, Inoue H, Tamura M, et al. (2012) The periodontal pathogen Porphyromonas gingivalis induces the Epstein-Barr virus lytic switch transactivator ZEBRA by histone modification. Biochimie 94, 839–846.
211.Segers ME & Lebeer S (2014) Towards a better understanding of Lactobacillus rhamnosus GG – host interactions. Microb Cell Fact 13, Suppl. 1, S7.
212.Elazab N, Mendy A, Gasana J, et al. (2013) Probiotic administration in early life, atopy, and asthma: a meta-analysis of clinical trials. Pediatrics 132, e666–e676.
213.World Health Organization, Food and Agricultural Organization of the United Nations (2006) Probiotics in Food. Health and Nutritional Properties and Guidelines for Evaluation. FAO Nutrition Paper, 85. Rome: FAO.
214.Hill C, Guarner F, Reid G, et al. (2014) Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol 11, 506–514.
215.Binnendijk KH & Rijkers GT (2013) What is a health benefit? An evaluation of EFSA opinions on health benefits with reference to probiotics. Benef Microbes 4, 223–230.
216.Petrof EO, Gloor GB, Vanner SJ, et al. (2013) Stool substitute transplant therapy for the eradication of Clostridium difficile infection: ‘RePOOPulating’ the gut. Microbiome 1, 3.
217.Ritchie ML & Romanuk TN (2012) A meta-analysis of probiotic efficacy for gastrointestinal diseases. PLOS ONE 7, e34938.