Skip to main content Accessibility help

Gut microbiota, the pharmabiotics they produce and host health

  • Elaine Patterson (a1) (a2) (a3), John F. Cryan (a1), Gerald F. Fitzgerald (a1) (a3), R. Paul Ross (a1) (a2), Timothy G. Dinan (a1) and Catherine Stanton (a1) (a2)...


A healthy gut microbiota plays many crucial functions in the host, being involved in the correct development and functioning of the immune system, assisting in the digestion of certain foods and in the production of health-beneficial bioactive metabolites or ‘pharmabiotics’. These include bioactive lipids (including SCFA and conjugated linoleic acid) antimicrobials and exopolysaccharides in addition to nutrients, including vitamins B and K. Alterations in the composition of the gut microbiota and reductions in microbial diversity are highlighted in many disease states, possibly rendering the host susceptible to infection and consequently negatively affecting innate immune function. Evidence is also emerging of microbially produced molecules with neuroactive functions that can have influences across the brain–gut axis. For example, γ-aminobutyric acid, serotonin, catecholamines and acetylcholine may modulate neural signalling within the enteric nervous system, when released in the intestinal lumen and consequently signal brain function and behaviour. Dietary supplementation with probiotics and prebiotics are the most widely used dietary adjuncts to modulate the gut microbiota. Furthermore, evidence is emerging of the interactions between administered microbes and dietary substrates, leading to the production of pharmabiotics, which may directly or indirectly positively influence human health.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Gut microbiota, the pharmabiotics they produce and host health
      Available formats

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Gut microbiota, the pharmabiotics they produce and host health
      Available formats

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Gut microbiota, the pharmabiotics they produce and host health
      Available formats


Corresponding author

* Corresponding author: Professor C. Stanton, email


Hide All
1. Ley, RE, Turnbaugh, PJ, Klein, S et al. (2006) Microbial ecology – human gut microbes associated with obesity. Nature 444, 10221023.
2. Qin, JJ, Li, RQ, Raes, J et al. (2010) A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464, 59–U70.
3. Backhed, F, Ding, H, Wang, T et al. (2004) The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A 101, 1571815723.
4. Maynard, CL, Elson, CO, Hatton, RD et al. (2012) Reciprocal interactions of the intestinal microbiota and immune system. Nature 489, 231241.
5. Marques, TM, Wall, R, Ross, RP et al. (2010) Programming infant gut microbiota: influence of dietary and environmental factors. Curr Opin Biotechnol 21, 149156.
6. Bouhnik, Y, Alain, S, Attar, A et al. (1999) Bacterial populations contaminating the upper gut in patients with small intestinal bacterial overgrowth syndrome. Am J Gastroenterol 94, 13271331.
7. Riordan, SM, McIver, CJ, Wakefield, D et al. (2001) Small intestinal mucosal immunity and morphometry in luminal overgrowth of indigenous gut flora. Am J Gastroenterol 96, 494500.
8. Maes, M, Kubera, M, Leunis, JC et al. (2013) In depression, bacterial translocation may drive inflammatory responses, oxidative and nitrosative stress (O&NS), and autoimmune responses directed against O&NS-damaged neoepitopes. Acta Psychiatr Scand 127, 344354.
9. Teltschik, Z, Wiest, R, Beisner, J et al. (2012) Intestinal bacterial translocation in rats with cirrhosis is related to compromised Paneth cell antimicrobial host defense. Hepatology 55, 11541163.
10. Koenig, JE, Spor, A, Scalfone, N et al. (2011) Succession of microbial consortia in the developing infant gut microbiome. Proc Natl Acad Sci U S A 108, Suppl. 1, 45784585.
11. Scholtens, PAMJ, Oozeer, R, Martin, R et al. (2012) The early settlers: intestinal microbiology in early life. Annu Rev Food Sci Technol 3, 425447.
12. Butel, MJ, Suau, A, Campeotto, F et al. (2007) Conditions of bifidobacterial colonization in preterm infants: a prospective analysis. J Pediatr Gastr Nutr 44, 577582.
13. Dominguez-Bello, MG, Costello, EK, Contreras, M et al. (2010) Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci U S A 107, 1197111975.
14. Bezirtzoglou, E, Tsiotsias, A & Welling, GW (2011) Microbiota profile in feces of breast- and formula-fed newborns by using fluorescence in situ hybridization (FISH). Anaerobe 17, 478482.
15. Fallani, M, Young, D, Scott, J et al. (2010) Intestinal microbiota of 6-week-old infants across Europe: geographic influence beyond delivery mode, breast-feeding, and antibiotics. J Pediatr Gastroenterol Nutr 51, 7784.
16. Hallab, JC, Leach, ST, Zhang, L et al. (2013) Molecular characterization of bacterial colonization in the preterm and term infant's intestine. Indian J Pediatr 80, 15.
17. Fouhy, F, Guinane, CM, Hussey, S et al. (2012) High-throughput sequencing reveals the incomplete, short-term recovery of infant gut microbiota following parenteral antibiotic treatment with ampicillin and gentamicin. Antimicrob Agents Chemother 56, 58115820.
18. Hussey, S, Wall, R, Gruffman, E et al. (2011) Parenteral antibiotics reduce bifidobacteria colonization and diversity in neonates. Int J Microbiol; available at
19. Palmer, C, Bik, EM, DiGiulio, DB et al. (2007) Development of the human infant intestinal microbiota. PLoS Biol 5, 15561573.
20. Penders, J, Thijs, C, Vink, C et al. (2006) Factors influencing the composition of the intestinal microbiota in early infancy. Pediatrics 118, 511521.
21. Huurre, A, Kalliomaki, M, Rautava, S et al. (2008) Mode of delivery – effects on gut microbiota and humoral immunity. Neonatology 93, 236240.
22. Fallani, M, Amarri, S, Uusijarvi, A et al. (2011) Determinants of the human infant intestinal microbiota after the introduction of first complementary foods in infant samples from five European centres. Microbiology 157, 13851392.
23. Yatsunenko, T, Rey, FE, Manary, MJ et al. (2012) Human gut microbiome viewed across age and geography. Nature 486, 222227.
24. Kurokawa, K, Itoh, T, Kuwahara, T et al. (2007) Comparative metagenomics revealed commonly enriched gene sets in human gut microbiomes. DNA Res 14, 169181.
25. Turnbaugh, PJ, Ridaura, VK, Faith, JJ et al. (2009) The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci Transl Med 1; available at
26. Guinane, CM & Cotter, PD (2013) Role of the gut microbiota in health and chronic gastrointestinal disease: understanding a hidden metabolic organ. Therap Adv Gastroenterol 6, 295308.
27. Vyas, U & Ranganathan, N (2012) Probiotics, prebiotics, and synbiotics: gut and beyond. Gastroenterol Res Pract; available at
28. Sanders, ME, Guarner, F, Guerrant, R et al. (2013) An update on the use and investigation of probiotics in health and disease. Gut 62, 787796.
29. FAO/WHO EC (2001) Report of a Joint Expert Consultation. Health and Nutritional Properties of Probiotics in Food Including Powder Milk and Live Lactic Acid Bacteria. http://wwwfaoorg/es/ESN/Probio/report
30. Cappello, C, Tremolaterra, F, Pascariello, A et al. (2013) A randomised clinical trial (RCT) of a symbiotic mixture in patients with irritable bowel syndrome (IBS): effects on symptoms, colonic transit and quality of life. Int J Colorectal Dis 28, 349358.
31. Whelan, K & Quigley, EM (2013) Probiotics in the management of irritable bowel syndrome and inflammatory bowel disease. Curr Opin Gastroenterol 29, 184189.
32. 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. J Am Med Assoc 307, 19591969.
33. Hickson, M (2011) Probiotics in the prevention of antibiotic-associated diarrhoea and Clostridium difficile infection. Therap Adv Gastroenterol 4, 185197.
34. Marques, TM, Cryan, JF, Shanahan, F et al. (2013) Gut microbiota modulation and implications for host health: dietary strategies to influence the gut–brain axis. Innov Food Sci Emerging Technol 22, 239247.
35. Saulnier, DM, Spinler, JK, Gibson, GR et al. (2009) Mechanisms of probiosis and prebiosis: considerations for enhanced functional foods. Curr Opin Biotechnol 20, 135141.
36. Preidis, GA & Versalovic, J (2009) Targeting the human microbiome with antibiotics, probiotics, and prebiotics: gastroenterology enters the metagenomics era. Gastroenterology 136, 20152031.
37. Hansen, CHF, Nielsen, DS, Kverka, M et al. (2012) Patterns of early gut colonization shape future immune responses of the host. PLoS ONE 7, e34043.
38. Moreau, MC, Ducluzeau, R, Guy-Grand, D et al. (1978) Increase in the population of duodenal immunoglobulin A plasmocytes in axenic mice associated with different living or dead bacterial strains of intestinal origin. Infect Immun 21, 532539.
39. Macpherson, AJ & Harris, NL (2004) Interactions between commensal intestinal bacteria and the immune system. Nat Rev Immunol 4, 478485.
40. Falk, PG, Hooper, LV, Midtvedt, T et al. (1998) Creating and maintaining the gastrointestinal ecosystem: what we know and need to know from gnotobiology. Microbiol Mol Biol Rev 62, 11571170.
41. Pollard, M & Sharon, N (1970) Responses of the Peyer's patches in germ-free mice to antigenic stimulation. Infect Immun 2, 96100.
42. Hoshi, H, Aijima, H, Horie, K et al. (1992) Lymph follicles and germinal centers in popliteal lymph nodes and other lymphoid tissues of germ-free and conventional rats. Tohoku J Exp Med 166, 297307.
43. Round, JL & Mazmanian, SK (2009) The gut microbiota shapes intestinal immune responses during health and disease (vol 9, pg 313, 2009). Nat Rev Immunol 9, 600600.
44. Imaoka, A, Matsumoto, S, Setoyama, H et al. (1996) Proliferative recruitment of intestinal intraepithelial lymphocytes after microbial colonization of germ-free mice. Eur J Immunol 26, 945948.
45. Umesaki, Y, Setoyama, H, Matsumoto, S et al. (1993) Expansion of alpha beta T-cell receptor-bearing intestinal intraepithelial lymphocytes after microbial colonization in germ-free mice and its independence from thymus. Immunology 79, 3237.
46. Abrams, GD, Bauer, H & Sprinz, H (1963) Influence of the normal flora on mucosal morphology and cellular renewal in the ileum. A comparison of germ-free and conventional mice. Lab Invest 12, 355364.
47. Sprinz, H, Kundel, DW, Dammin, GJ et al. (1961) The response of the germfree guinea pig to oral bacterial challenge with Escherichia coli and Shigella flexneri . Am J Pathol 39, 681695.
48. Zachar, Z & Savage, DC (1979) Microbial interference and colonization of the murine gastrointestinal-tract by Listeria monocytogenes . Infect Immun 23, 168174.
49. Hooper, LV & Macpherson, AJ (2010) Immune adaptations that maintain homeostasis with the intestinal microbiota. Nat Rev Immunol 10, 159169.
50. Mazmanian, SK, Round, JL & Kasper, DL (2008) A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453, 620625.
51. Mazmanian, SK, Liu, CH, Tzianabos, AO et al. (2005) An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 122, 107118.
52. 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, 227236.
53. Martinez, C, Antolin, M, Santos, J et al. (2008) Unstable composition of the fecal microbiota in ulcerative colitis during clinical remission. Am J Gastroenterol 103, 643648.
54. Manichanh, C, Borruel, N, Casellas, F et al. (2012) The gut microbiota in IBD. Nat Rev Gastroenterol Hepatol 9, 599608.
55. Morgan, XC, Tickle, TL, Sokol, H et al. (2012) Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol 13, R79.
56. Manichanh, C, Rigottier-Gois, L, Bonnaud, E et al. (2006) Reduced diversity of faecal microbiota in Crohn's disease revealed by a metagenomic approach. Gut 55, 205211.
57. Sokol, H, Seksik, P, Rigottier-Gois, L et al. (2006) Specificities of the fecal microbiota in inflammatory bowel disease. Inflamm Bowel Dis 12, 106111.
58. Clayton, EM, Rea, MC, Shanahan, F et al. (2009) The vexed relationship between Clostridium difficile and inflammatory bowel disease: an assessment of carriage in an outpatient setting among patients in remission. Am J Gastroenterol 104, 11621169.
59. Larsen, N, Vogensen, FK, van den Berg, FW et al. (2012) Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS ONE 5, e9085.
60. Qin, J, Li, Y, Cai, Z et al. (2012) A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490, 5560.
61. Roesch, LF, Lorca, GL, Casella, G et al. (2009) Culture-independent identification of gut bacteria correlated with the onset of diabetes in a rat model. ISME J 3, 536548.
62. Brown, CT, Davis-Richardson, AG, Giongo, A et al. (2011) Gut microbiome metagenomics analysis suggests a functional model for the development of autoimmunity for type 1 diabetes. PLoS ONE 6, e25792.
63. Giongo, A, Gano, KA, Crabb, DB et al. (2011) Toward defining the autoimmune microbiome for type 1 diabetes. ISME J 5, 8291.
64. de Goffau, MC, Luopajarvi, K, Knip, M et al. (2013) Fecal microbiota composition differs between children with beta-cell autoimmunity and those without. Diabetes 62, 12381244.
65. Ley, RE (2010) Obesity and the human microbiome. Curr Opin Gastroenterol 26, 511.
66. Ley, RE, Backhed, F, Turnbaugh, P et al. (2005) Obesity alters gut microbial ecology. Proc Natl Acad Sci U S A 102, 1107011075.
67. Tilg, H & Kaser, A (2011) Gut microbiome, obesity, and metabolic dysfunction. J Clin Invest 121, 21262132.
68. Turnbaugh, PJ, Ley, RE, Mahowald, MA et al. (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 10271031.
69. Schwiertz, A, Taras, D, Schafer, K et al. (2010) Microbiota and SCFA in lean and overweight healthy subjects. Obesity (Silver Spring) 18, 190195.
70. Murphy, EF, Cotter, PD, Healy, S et al. (2010) Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models. Gut 59, 16351642.
71. Cani, PD, Amar, J, Iglesias, MA et al. (2007) Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56, 17611772.
72. Cani, PD, Bibiloni, R, Knauf, C et al. (2008) Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 57, 14701481.
73. Vance, DE (2008) Role of phosphatidylcholine biosynthesis in the regulation of lipoprotein homeostasis. Curr Opin Lipidol 19, 229234.
74. Dumas, ME, Barton, RH, Toye, A et al. (2006) Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice. Proc Natl Acad Sci U S A 103, 1251112516.
75. Prentiss, PG, Rosen, H, Brown, N et al. (1961) The metabolism of choline by the germfree rat. Arch Biochem Biophys 94, 424429.
76. Wang, Z, Klipfell, E, Bennett, BJ et al. (2011) Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472, 5763.
77. Tang, WHW, Wang, ZE, Levison, BS et al. (2013) Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. New Engl J Med 368, 15751584.
78. Shanahan, F (2009) Therapeutic implications of manipulatingand mining the microbiota. J Physiol 587, 41754179.
79. Said, HM (2011) Intestinal absorption of water-soluble vitamins in health and disease. Biochem J 437, 357372.
80. Wall, R, Ross, RP, Shanahan, F et al. (2009) Metabolic activity of the enteric microbiota influences the fatty acid composition of murine and porcine liver and adipose tissues. Am J Clin Nutr 89, 13931401.
81. Wall, R, Marques, TM, O'Sullivan, O et al. (2012) Contrasting effects of Bifidobacterium breve NCIMB 702258 and Bifidobacterium breve DPC 6330 on the composition of murine brain fatty acids and gut microbiota. Am J Clin Nutr 95, 12781287.
82. Barrett, E, Fitzgerald, P, Dinan, TG et al. (2012) Bifidobacterium breve with alpha-linolenic acid and linoleic acid alters fatty acid metabolism in the Maternal Separation Model of Irritable Bowel Syndrome. PLoS ONE 7, e48159.
83. Hennessy, AA, Barrett, E, Ross, RP et al. (2012) The production of conjugated alpha-linolenic, gamma-linolenic and stearidonic acids by strains of bifidobacteria and propionibacteria. Lipids 47, 313327.
84. Lee, HY, Park, JH, Seok, SH et al. (2006) Human originated bacteria, Lactobacillus rhamnosus PL60, produce conjugated linoleic acid and show anti-obesity effects in diet-induced obese mice. Biochim Biophys Acta 1761, 736744.
85. Lee, K, Paek, K, Lee, HY et al. (2007) Antiobesity effect of trans-10, cis-12-conjugated linoleic acid-producing Lactobacillus plantarum PL62 on diet-induced obese mice. J Appl Microbiol 103, 11401146.
86. Wall, R, Ross, RP, Shanahan, F et al. (2010) Impact of administered bifidobacterium on murine host fatty acid composition. Lipids 45, 429436.
87. Nakajima, H, Suzuki, Y, Kaizu, H et al. (1992) Cholesterol lowering activity of ropy fermented milk. J Food Sci 57, 13271329.
88. Vinderola, G, Perdigon, G, Duarte, J et al. (2006) Effects of the oral administration of the exopolysaccharide produced by Lactobacillus kefiranofaciens on the gut mucosal immunity. Cytokine 36, 254260.
89. Ko, CY, Lin, HTV & Tsai, GJ (2013) Gamma-aminobutyric acid production in black soybean milk by Lactobacillus brevis FPA 3709 and the antidepressant effect of the fermented product on a forced swimming rat model. Process Biochem 48, 559568.
90. 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, 1605016055.
91. Desbonnet, L, Garrett, L, Clarke, G et al. (2008) The probiotic Bifidobacteria infantis: an assessment of potential antidepressant properties in the rat. J Psychiatr Res 43, 164174.
92. LeBlanc, JG, Milani, C, de Giori, GS et al. (2013) Bacteria as vitamin suppliers to their host: a gut microbiota perspective. Curr Opin Biotechnol 24, 160168.
93. Deguchi, Y, Morishita, T & Mutai, M (1985) Comparative studies on synthesis of water-soluble vitamins among human species of Bifidobacteria . Agric Biol Chem Tokyo 49, 1319.
94. Noda, H, Akasaka, N & Ohsugi, M (1994) Biotin production by Bifidobacteria . J Nutr Sci Vitaminol (Tokyo) 40, 181188.
95. Pompei, A, Cordisco, L, Amaretti, A et al. (2007) Folate production by Bifidobacteria as a potential probiotic property. Appl Environ Microbiol 73, 179185.
96. Szulc, P, Arlot, M, Chapuy, MC et al. (1994) Serum undercarboxylated osteocalcin correlates with hip bone mineral density in elderly women. J Bone Miner Res 9, 15911595.
97. Knapen, MH, Nieuwenhuijzen Kruseman, AC, Wouters, RS et al. (1998) Correlation of serum osteocalcin fractions with bone mineral density in women during the first 10 years after menopause. Calcif Tissue Int 63, 375379.
98. Szulc, P, Chapuy, MC, Meunier, PJ et al. (1993) Serum undercarboxylated osteocalcin Is a marker of the risk of hip fracture in elderly women. J Clin Invest 91, 17691774.
99. Luukinen, H, Kakonen, SM, Pettersson, K et al. (2000) Strong prediction of fractures among older adults by the ratio of carboxylated to total serum osteocalcin. J Bone Miner Res 15, 24732478.
100. Geleijnse, JM, Vermeer, C, Grobbee, DE et al. (2004) Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. J Nutr 134, 31003105.
101. Roessner, CA, Huang, KX, Warren, MJ et al. (2002) Isolation and characterization of 14 additional genes specifying the anaerobic biosynthesis of cobalamin (vitamin B12) in Propionibacterium freudenreichii (P. shermanii). Microbiology 148, 18451853.
102. Taranto, MP, Vera, JL, Hugenholtz, J et al. (2003) Lactobacillus reuteri CRL1098 produces cobalamin. J Bacteriol 185, 56435647.
103. Saulnier, DM, Santos, F, Roos, S et al. (2011) Exploring metabolic pathway reconstruction and genome-wide expression profiling in Lactobacillus reuteri to define functional probiotic features. PLoS ONE 6, e18783.
104. Klaassens, ES, Boesten, RJ, Haarman, M et al. (2009) Mixed-species genomic microarray analysis of fecal samples reveals differential transcriptional responses of bifidobacteria in breast- and formula-fed infants. Appl Environ Microbiol 75, 26682676.
105. Klaassens, ES, Ben-Amor, K, Vriesema, A et al. (2011) The fecal bifidobacterial transcriptome of adults: a microarray approach. Gut Microbes 2, 217226.
106. Gosalbes, MJ, Durban, A, Pignatelli, M et al. (2011) Metatranscriptomic approach to analyze the functional human gut microbiota. PLoS ONE 6, e17447.
107. Belury, MA (2002) Inhibition of carcinogenesis by conjugated linoleic acid: potential mechanisms of action. J Nutr 132, 29952998.
108. Benjamin, S & Spener, F (2009) Conjugated linoleic acids as functional food: an insight into their health benefits. Nutr Metab (Lond) 6, 36.
109. Bhattacharya, A, Banu, J, Rahman, M et al. (2006) Biological effects of conjugated linoleic acids in health and disease. J Nutr Biochem 17, 789810.
110. Brownbill, RA, Petrosian, M & Ilich, JZ (2005) Association between dietary conjugated linoleic acid and bone mineral density in postmenopausal women. J Am Coll Nutr 24, 177181.
111. Chin, SF, Storkson, JM, Albright, KJ et al. (1994) Conjugated linoleic acid is a growth factor for rats as shown by enhanced weight gain and improved feed efficiency. J Nutr 124, 23442349.
112. Churruca, I, Fernandez-Quintela, A & Portillo, MP (2009) Conjugated linoleic acid isomers: differences in metabolism and biological effects. Biofactors 35, 105111.
113. Jaudszus, A, Foerster, M, Kroegel, C et al. (2005) Cis-9, trans-11-CLA exerts anti-inflammatory effects in human bronchial epithelial cells and eosinophils: comparison to trans-10, cis-12-CLA and to linoleic acid. Biochim Biophys Acta 1737, 111118.
114. Kelley, NS, Hubbard, NE & Erickson, KL (2007) Conjugated linoleic acid isomers and cancer. J Nutr 137, 25992607.
115. Nagao, K & Yanagita, T (2005) Conjugated fatty acids in food and their health benefits. J Biosci Bioeng 100, 152157.
116. Pariza, MW, Park, Y & Cook, ME (2001) The biologically active isomers of conjugated linoleic acid. Prog Lipid Res 40, 283298.
117. Silveira, MB, Carraro, R, Monereo, S et al. (2007) Conjugated linoleic acid (CLA) and obesity. Public Health Nutr 10, 11811186.
118. Valeille, K, Ferezou, J, Parquet, M et al. (2006) The natural concentration of the conjugated linoleic acid, cis-9, trans-11, in milk fat has antiatherogenic effects in hyperlipidemic hamsters. J Nutr 136, 13051310.
119. Watras, AC, Buchholz, AC, Close, RN et al. (2007) The role of conjugated linoleic acid in reducing body fat and preventing holiday weight gain. Int J Obes (Lond) 31, 481487.
120. Mele, MC, Cannelli, G, Carta, G et al. (2013) Metabolism of c9, t11-conjugated linoleic acid (CLA) in humans. Prostag Leukotr Ess 89, 115119.
121. Coakley, M, Ross, RP, Nordgren, M et al. (2003) Conjugated linoleic acid biosynthesis by human-derived Bifidobacterium species. J Appl Microbiol 94, 138145.
122. Rosberg-Cody, E, Ross, RP, Hussey, S et al. (2004) Mining the microbiota of the neonatal gastrointestinal tract for conjugated linoleic acid-producing bifidobacteria. Appl Environ Microbiol 70, 46354641.
123. Nobre, ME, Correia, AO, Borges Mde, B et al. (2013) Eicosapentaenoic acid and docosahexaenoic acid exert anti-inflammatory and antinociceptive effects in rodents at low doses. Nutr Res 33, 422433.
124. Hu, GX, Chen, GR, Xu, H et al. (2010) Activation of the AMP activated protein kinase by short-chain fatty acids is the main mechanism underlying the beneficial effect of a high fiber diet on the metabolic syndrome. Med Hypotheses 74, 123126.
125. Gao, Z, Yin, J, Zhang, J et al. (2009) Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes 58, 15091517.
126. Blouin, JM, Penot, G, Collinet, M et al. (2011) Butyrate elicits a metabolic switch in human colon cancer cells by targeting the pyruvate dehydrogenase complex. Int J Cancer 128, 25912601.
127. Scharlau, D, Borowicki, A, Habermann, N et al. (2009) Mechanisms of primary cancer prevention by butyrate and other products formed during gut flora-mediated fermentation of dietary fibre. Mutat Res 682, 3953.
128. Tang, Y, Chen, Y, Jiang, H et al. (2011) G-protein-coupled receptor for short-chain fatty acids suppresses colon cancer. Int J Cancer 128, 847856.
129. Harig, JM, Soergel, KH, Komorowski, RA et al. (1989) Treatment of diversion colitis with short-chain-fatty acid irrigation. N Engl J Med 320, 2328.
130. Breuer, RI, Buto, SK, Christ, ML et al. (1991) Rectal irrigation with short-chain fatty acids for distal ulcerative colitis. Preliminary report. Dig Dis Sci 36, 185187.
131. Vernia, P, Marcheggiano, A, Caprilli, R et al. (1995) Short-chain fatty acid topical treatment in distal ulcerative colitis. Aliment Pharmacol Ther 9, 309313.
132. Scheppach, W (1996) Treatment of distal ulcerative colitis with short-chain fatty acid enemas. A placebo-controlled trial. German-Austrian SCFA Study Group. Dig Dis Sci 41, 22542259.
133. Di Sabatino, A, Morera, R, Ciccocioppo, R et al. (2005) Oral butyrate for mildly to moderately active Crohn's disease. Aliment Pharmacol Ther 22, 789794.
134. den Besten, G, van Eunen, K, Groen, AK et al. (2013) The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res 54, 23252340.
135. Donohoe, DR, Garge, N, Zhang, X et al. (2011) The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metab 13, 517526.
136. Tremaroli, V & Backhed, F (2012) Functional interactions between the gut microbiota and host metabolism. Nature 489, 242249.
137. Maslowski, KM, Vieira, AT, Ng, A et al. (2009) Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461, 12821286.
138. Sina, C, Gavrilova, O, Forster, M et al. (2009) G protein-coupled receptor 43 is essential for neutrophil recruitment during intestinal inflammation. J Immunol 183, 75147522.
139. Tolhurst, G, Heffron, H, Lam, YS et al. (2012) Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes 61, 364371.
140. Stack, HM, Kearney, N, Stanton, C et al. (2010) Association of beta-glucan endogenous production with increased stress tolerance of intestinal lactobacilli. Appl Environ Microbiol 76, 500507.
141. Kitazawa, H, Harata, T, Uemura, J et al. (1998) Phosphate group requirement for mitogenic activation of lymphocytes by an extracellular phosphopolysaccharide from Lactobacillus delbrueckii ssp. bulgaricus. Int J Food Microbiol 40, 169175.
142. Maeda, H, Zhu, X, Omura, K et al. (2004) Effects of an exopolysaccharide (kefiran) on lipids, blood pressure, blood glucose, and constipation. Biofactors 22, 197200.
143. Korakli, M, Ganzle, MG & Vogel, RF (2002) Metabolism by bifidobacteria and lactic acid bacteria of polysaccharides from wheat and rye, and exopolysaccharides produced by Lactobacillus sanfranciscensis . J Appl Microbiol 92, 958965.
144. O'Connor, E, Barrett, E, Fitzgerald, G et al. (2005) Production of vitamins, exopolysaccharides and bacteriocins by probiotic bacteria. Probiotic Dairy Products 167194.
145. Theuwissen, E & Mensink, RP (2008) Water-soluble dietary fibers and cardiovascular disease. Physiol Behav 94, 285292.
146. Akramiene, D, Kondrotas, A, Didziapetriene, J et al. (2007) Effects of beta-glucans on the immune system. Medicina 43, 597606.
147. Hida, TH, Ishibashi, K, Miura, NN et al. (2009) Cytokine induction by a linear 1,3-glucan, curdlan-oligo, in mouse leukocytes in vitro . Inflamm Res 58, 914.
148. Tsoni, SV & Brown, GD (2008) Beta-glucans and Dectin-1. Ann N Y Acad Sci 1143, 4560.
149. Volman, JJ, Ramakers, JD & Plat, J (2008) Dietary modulation of immune function by beta-glucans. Physiol Behav 94, 276284.
150. Wilson, TA, Nicolosi, RJ, Delaney, B et al. (2004) Reduced and high molecular weight barley beta-glucans decrease plasma total and non-HDL-cholesterol in hypercholesterolemic Syrian golden hamsters. J Nutr 134, 26172622.
151. Shin, HD, Yang, KJ, Park, BR et al. (2007) Antiosteoporotic effect of polycan, beta-glucan from Aureobasidium, in ovariectomized osteoporotic mice. Nutrition 23, 853860.
152. Gu, Y, Fujimiya, Y, Itokawa, Y et al. (2008) Tumoricidal effects of beta-glucans: mechanisms include both antioxidant activity plus enhanced systemic and topical immunity. Nutr Cancer 60, 685691.
153. Mantovani, MS, Bellini, MF, Angeli, JP et al. (2008) Beta-glucans in promoting health: prevention against mutation and cancer. Mutat Res 658, 154161.
154. Beck, EJ, Tapsell, LC, Batterham, MJ et al. (2009) Increases in peptide Y–Y levels following oat beta-glucan ingestion are dose-dependent in overweight adults. Nutr Res 29, 705709.
155. Beck, EJ, Tosh, SM, Batterham, MJ et al. (2009) Oat beta-glucan increases postprandial cholecystokinin levels, decreases insulin response and extends subjective satiety in overweight subjects. Mol Nutr Food Res 53, 13431351.
156. Fanning, S, Hall, LJ & van Sinderen, D (2012) Bifidobacterium breve UCC2003 surface exopolysaccharide production is a beneficial trait mediating commensal-host interaction through immune modulation and pathogen protection. Gut Microbes 3, 420425.
157. Collins, SM, Surette, M & Bercik, P (2012) The interplay between the intestinal microbiota and the brain. Nat Rev Microbiol 10, 735742.
158. Forsythe, P, Sudo, N, Dinan, T et al. (2010) Mood and gut feelings. Brain Behav Immun 24, 916.
159. Neufeld, KM, Kang, N, Bienenstock, J et al. (2011) Reduced anxiety-like behavior and central neurochemical change in germ-free mice. Neurogastroenterol Motil 23, 255264, e119.
160. 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, 263275.
161. de Theije, CGM, Wu, JB, da Silva, SL et al. (2011) Pathways underlying the gut-to-brain connection in autism spectrum disorders as future targets for disease management. Eur J Pharmacol 668, S70S80.
162. Desbonnet, L, Clarke, G, Shanahan, F et al. (2013) Microbiota is essential for social development in the mouse. Mol Psychiatry 19, 146148.
163. Finegold, SM, Dowd, SE, Gontcharova, V et al. (2010) Pyrosequencing study of fecal microflora of autistic and control children. Anaerobe 16, 444453.
164. Heijtza, RD, Wang, SG, Anuar, F et al. (2011) Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci U S A 108, 30473052.
165. 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, 666673.
166. Messaoudi, M, Lalonde, R, Violle, N et al. (2011) Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br J Nutr 105, 755764.
167. Hsiao, EY, McBride, SW, Hsien, S et al. (2013) Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155, 14511463.
168. Henriksen, C, Haugholt, K, Lindgren, M et al. (2008) Improved cognitive development among preterm infants attributable to early supplementation of human milk with docosahexaenoic acid and arachidonic acid. Pediatrics 121, 11371145.
169. Yurko-Mauro, K, McCarthy, D, Rom, D et al. (2010) Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline. Alzheimers Dement 6, 456464.
170. Dinan, TG, Stanton, C & Cryan, JF (2013) Psychobiotics: a novel class of psychotropic. Biol Psychiatry 74, 720726.
171. Cryan, JF & O'Mahony, SM (2011) The microbiome–gut–brain axis: from bowel to behavior. Neurogastroenterol Motil 23, 187192.
172. Cryan, JF & Kaupmann, K (2005) Don't worry ‘B’ happy!: a role for GABA(B) receptors in anxiety and depression. Trends Pharmacol Sci 26, 3643.
173. Schousboe, A & Waagepetersen, HS (2007) GABA: homeostatic and pharmacological aspects. Prog Brain Res 160, 919.
174. Komatsuzaki, N, Nakamura, T, Kimura, T et al. (2008) Characterization of glutamate decarboxylase from a high gamma-aminobutyric acid (GABA)-producer, Lactobacillus paracasei . Biosci Biotechnol Biochem 72, 278285.
175. Higuchi, T, Hayashi, H & Abe, K (1997) Exchange of glutamate and gamma-aminobutyrate in a Lactobacillus strain. J Bacteriol 179, 33623364.
176. Barrett, E, Ross, RP, O'Toole, PW et al. (2012) Gamma-aminobutyric acid production by culturable bacteria from the human intestine. J Appl Microbiol 113, 411417.
177. Wikoff, WR, Anfora, AT, Liu, J et al. (2009) Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc Natl Acad Sci U S A 106, 36983703.
178. 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, 263267.
179. Bailey, MT & Coe, CL (1999) Maternal separation disrupts the integrity of the intestinal microflora in infant rhesus monkeys. Dev Psychobiol 35, 146155.
180. Tsavkelova, EA, Botvinko, IV, Kudrin, VS et al. (2000) Detection of neurotransmitter amines in microorganisms with the use of high-performance liquid chromatography. Dokl Biochem 372, 115117.
181. Asano, Y, Hiramoto, T, Nishino, R et al. (2012) Critical role of gut microbiota in the production of biologically active, free catecholamines in the gut lumen of mice. Am J Physiol Gastrointest Liver Physiol 303, G1288G1295.
182. Girvin, GT & Stevenson, JW (1954) Cell free choline acetylase from Lactobacillus plantarum . Can J Biochem Physiol 32, 131146.
183. Rowatt, E (1948) The relation of pantothenic acid to acetylcholine formation by a strain of Lactobacillus plantarum . J Gen Microbiol 2, 2530.
184. Horiuchi, Y, Kimura, R, Kato, N et al. (2003) Evolutional study on acetylcholine expression. Life Sci 72, 17451756.
185. Cryan, JF & Dinan, TG (2012) Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci 13, 701712.


Gut microbiota, the pharmabiotics they produce and host health

  • Elaine Patterson (a1) (a2) (a3), John F. Cryan (a1), Gerald F. Fitzgerald (a1) (a3), R. Paul Ross (a1) (a2), Timothy G. Dinan (a1) and Catherine Stanton (a1) (a2)...


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed