Skip to main content Accessibility help
×
Home

Towards microbial fermentation metabolites as markers for health benefits of prebiotics

  • Kristin A. Verbeke (a1), Alan R. Boobis (a2), Alessandro Chiodini (a3), Christine A. Edwards (a4), Anne Franck (a5), Michiel Kleerebezem (a6), Arjen Nauta (a7), Jeroen Raes (a8), Eric A. F. van Tol (a9) and Kieran M. Tuohy (a10)...

Abstract

Available evidence on the bioactive, nutritional and putative detrimental properties of gut microbial metabolites has been evaluated to support a more integrated view of how prebiotics might affect host health throughout life. The present literature inventory targeted evidence for the physiological and nutritional effects of metabolites, for example, SCFA, the potential toxicity of other metabolites and attempted to determine normal concentration ranges. Furthermore, the biological relevance of more holistic approaches like faecal water toxicity assays and metabolomics and the limitations of faecal measurements were addressed. Existing literature indicates that protein fermentation metabolites (phenol, p-cresol, indole, ammonia), typically considered as potentially harmful, occur at concentration ranges in the colon such that no toxic effects are expected either locally or following systemic absorption. The endproducts of saccharolytic fermentation, SCFA, may have effects on colonic health, host physiology, immunity, lipid and protein metabolism and appetite control. However, measuring SCFA concentrations in faeces is insufficient to assess the dynamic processes of their nutrikinetics. Existing literature on the usefulness of faecal water toxicity measures as indicators of cancer risk seems limited. In conclusion, at present there is insufficient evidence to use changes in faecal bacterial metabolite concentrations as markers of prebiotic effectiveness. Integration of results from metabolomics and metagenomics holds promise for understanding the health implications of prebiotic microbiome modulation but adequate tools for data integration and interpretation are currently lacking. Similarly, studies measuring metabolite fluxes in different body compartments to provide a more accurate picture of their nutrikinetics are needed.

    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org 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 @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ 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.

      Towards microbial fermentation metabolites as markers for health benefits of prebiotics
      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.

      Towards microbial fermentation metabolites as markers for health benefits of prebiotics
      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.

      Towards microbial fermentation metabolites as markers for health benefits of prebiotics
      Available formats
      ×

Copyright

This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.

Corresponding author

*Corresponding author: ILSI Europe a.i.s.b.l., Avenue E. Mounier 83, Box 6, 1200 Brussels, Belgium; fax +32 2 762 00 44; email publications@ilsieurope.be

References

Hide All
1Scott, KP, Gratz, SW, Sheridan, PO, et al. (2013) The influence of diet on the gut microbiota. Pharmacol Res 69, 5260.
2Qin, JJ, Li, RQ, Raes, J, et al. (2010) A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464, 5965.
3Nicholson, JK, Holmes, E, Kinross, J, et al. (2012) Host-gut microbiota metabolic interactions. Science 336, 12621267.
4Blaut, M & Clavel, T (2007) Metabolic diversity of the intestinal microbiota: implications for health and disease. J Nutr 137, 751S755S.
5Marchesi, J & Shanahan, F (2007) The normal intestinal microbiota. Curr Opin Infect Dis 20, 508513.
6Hooper, LV, Littman, DR & Macpherson, AJ (2012) Interactions between the microbiota and the immune system. Science 336, 12681273.
7Roberfroid, M, Gibson, GR, Hoyles, L, et al. (2010) Prebiotic effects: metabolic and health benefits. Br J Nutr 104, Suppl. 2, S1S63.
8Gibson, GR & Roberfroid, MB (1995) Dietary modulation of the human colonic microbiota - introducing the concept of prebiotics. J Nutr 125, 14011412.
9Mahowald, MA, Rey, FE, Seedorf, H, et al. (2009) Characterizing a model human gut microbiota composed of members of its two dominant bacterial phyla. Proc Natl Acad Sci U S A 106, 58595864.
10den 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.
11Cook, SI & Sellin, JH (1998) Review Article: short chain fatty acids in health and disease. Aliment Pharmacol Ther 12, 499507.
12Topping, DL & Clifton, PM (2001) Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol Rev 81, 10311064.
13Freeland, KR (2010) Wilson C & Wolever TMS Adaptation of colonic fermentation and glucagon-like peptide-1 secretion with increased wheat fibre intake for 1 year in hyperinsulinaemic human subjects. Br J Nutr 103, 8290.
14Wolever, TMS, Josse, RG, Leiter, LA, et al. (1997) Time of day and glucose tolerance status affect serum short-chain fatty acid concentrations in humans. Metabolism 46, 805811.
15Edwards, CA, Parrett, AM, Balmer, SE, et al. (1994) Faecal short chain fatty acids in breast-fed and formula-fed babies. Acta Paediatr 83, 459462.
16Knol, J, Scholtens, P, Kafka, C, et al. (2005) Colon microflora in infants fed formula with galacto- and fructo-oligosaccharides: more like breast-fed infants. J Pediatr Gastroenterol Nutr 40, 3642.
17Midtvedt, AC (1992) & Midtvedt T Production of short chain fatty-acids by the intestinal microflora during the 1st 2 years of human life. J Pediatr Gastroenterol Nutr 15, 395403.
18Mariat, D, Firmesse, O, Levenez, F, et al. (2009) The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age. BMC Microbiol 9, 123.
19Andrieux, C, Membre, JM, Cayuela, C, et al. (2002) Metabolic characteristics of the faecal microflora in humans from three age groups. Scand J Gastroenterol 37, 792798.
20Gill, CIR, Heavey, P, McConville, E, et al. (2007) Effect of fecal water on an in vitro model of colonic mucosal barrier function. Nutr Cancer 57, 5965.
21Roediger, WE (1982) Utilization of nutrients by isolated epithelial-cells of the rat colon. Gastroenterology 83, 424429.
22Wong, JMW, de Souza, R, Kendall, CWC, et al. (2006) Colonic health: fermentation and short chain fatty acids. J Clin Gastroenterol 40, 235243.
23Layden, BT, Yalamanchi, SK, Wolever, TMS, et al. (2012) Negative association of acetate with visceral adipose tissue and insulin levels. Diabetes Metab Syndr Obes 5, 4955.
24Frost, G, Sleeth, ML, Sahuri-Arisoylu, M, et al. (2014) The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nat Commun 5, 3611.
25Kimura, I, Inoue, D, Maeda, T, et al. (2011) Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41). Proc Natl Acad Sci U S A 108, 80308035.
26Al-Lahham, S, Roelofsen, H, Rezaee, F, et al. (2012) Propionic acid affects immune status and metabolism in adipose tissue from overweight subjects. Eur J Clin Invest 42, 357364.
27Lin, HV, Frassetto, A, Kowalik, EJ Jr, et al. (2012) Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLOS ONE 7, e35240.
28Scheppach, W, Sommer, H, Kirchner, T, et al. (1992) Effect of butyrate enemas on the colonic mucosa in distal ulcerative-colitis. Gastroenterology 103, 5156.
29Fung, KYC, Cosgrove, L, Lockett, T, et al. (2012) A review of the potential mechanisms for the lowering of colorectal oncogenesis by butyrate. Br J Nutr 108, 820831.
30Fung, KYC, Brierley, GV, Henderson, S, et al. (2011) Butyrate-induced apoptosis in HCT116 colorectal cancer cells includes induction of a cell stress response. J Proteome Res 10, 18601869.
31Shao, YF, Gao, ZH, Marks, PA, et al. (2004) Apoptotic and autophagic cell death induced by histone deacetylase inhibitors. Proc Natl Acad Sci U S A 101, 1803018035.
32Sauer, J, Richter, KK & Pool-Zobel, BL (2007) Physiological concentrations of butyrate favorably modulate genes of oxidative and metabolic stress in primary human colon cells. J Nutr Biochem 18, 736745.
33Ploger, S, Stumpff, F, Penner, GB, et al. (2012) Microbial butyrate and its role for barrier function in the gastrointestinal tract. Ann N Y Acad Sci 1258, 5259.
34Arpaia, N, Campbell, C, Fan, X, et al. (2013) Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504, 451455.
35De Vadder, F, Kovatcheva-Datchary, P, Goncalves, D, et al. (2014) Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell 156, 8496.
36Faber, TA, Hopkins, AC, Middelbos, IS, et al. (2011) Galactoglucomannan oligosaccharide supplementation affects nutrient digestibility, fermentation end-product production, and large bowel microbiota of the dog. J Anim Sci 89, 103112.
37Theil, PK, Jorgensen, H, Serena, A, et al. (2011) Products deriving from microbial fermentation are linked to insulinaemic response in pigs fed breads prepared from whole-wheat grain and wheat and rye ingredients. Br J Nutr 105, 373383.
38Van Immerseel, F, Russell, JB, Flythe, MD, et al. (2006) The use of organic acids to combat Salmonella in poultry: a mechanistic explanation of the efficacy. Avian Pathol 35, 182188.
39Petry, N, Egli, I, Chassard, C, et al. (2012) Inulin modifies the bifidobacteria population, fecal lactate concentration, and fecal pH but does not influence iron absorption in women with low iron status. Am J Clin Nutr 96, 325331.
40Linetzky Waitzberg, D, Alves Pereira, CC, Logullo, L, et al. (2012) Microbiota benefits after inulin and partially hydrolized guar gum supplementation: a randomized clinical trial in constipated women. Nutr Hosp 27, 123129.
41Slavin, J & Feirtag, J (2011) Chicory inulin does not increase stool weight or speed up intestinal transit time in healthy male subjects. Food Funct 2, 7277.
42Worthley, DL, Le Leu, RK, Whitehall, VL, et al. (2009) A human, double-blind, placebo-controlled, crossover trial of prebiotic, probiotic, and synbiotic supplementation: effects on luminal, inflammatory, epigenetic, and epithelial biomarkers of colorectal cancer. Am J Clin Nutr 90, 578586.
43Costabile, A, Klinder, A, Fava, F, et al. (2007) Whole-grain wheat breakfast cereal has a prebiotic effect on the human gut microbiota: a double-blind, placebo-controlled, crossover study. Br J Nutr 99, 110120.
44Costabile, A, Fava, F, Roytio, H, et al. (2012) Impact of polydextrose on the faecal microbiota: a double-blind, crossover, placebo-controlled feeding study in healthy human subjects. Br J Nutr 108, 471481.
45Timm, DA, Stewart, ML, Hospattankar, A, et al. (2010) Wheat dextrin, psyllium, and inulin produce distinct fermentation patterns, gas volumes, and short-chain fatty acid profiles in vitro. J Med Food 13, 961966.
46Pylkas, AM, Juneja, LR & Slavin, JL (2005) Comparison of different fibers for in vitro production of short chain fatty acids by intestinal microflora. J Med Food 8, 113116.
47Connolly, ML, Lovegrove, JA & Tuohy, KM (2010) In vitro evaluation of the microbiota modulation abilities of different sized whole oat grain flakes. Anaerobe 16, 483488.
48Cuervo, A, Salazar, N, Ruas-Madiedo, P, et al. (2013) Fiber from a regular diet is directly associated with fecal short-chain fatty acid concentrations in the elderly. Nutr Res 33, 811816.
49Kedia, G, Vazquez, JA, Charalampopoulos, D, et al. (2009) In vitro fermentation of oat bran obtained by debranning with a mixed culture of human fecal bacteria. Curr Microbiol 58, 338342.
50Hughes, SA, Shewry, PR, Gibson, GR, et al. (2008) In vitro fermentation of oat and barley derived β-glucans by human faecal microbiota. FEMS Microbiol Ecol 64, 482493.
51Laurentin, A & Edwards, CA (2004) Differential fermentation of glucose-based carbohydrates in vitro by human faecal bacteria – a study of pyrodextrinised starches from different sources. Eur J Nutr 43, 183189.
52Nordlund, E, Aura, AM, Mattila, I, et al. (2012) Formation of phenolic microbial metabolites and short-chain fatty acids from rye, wheat, and oat bran and their fractions in the metabolical in vitro colon model. J Agric Food Chem 60, 81348145.
53Nilsson, A, Johansson, E, Ekstrom, L, et al. (2013) Effects of a brown beans evening meal on metabolic risk markers and appetite regulating hormones at a subsequent standardized breakfast: a randomized cross-over study. PLOS ONE 8, e59985.
54Van den Abbeele, P, Venema, K, van de Wiele, T, et al. (2013) Different human gut models reveal the distinct fermentation patterns of arabinoxylan versus inulin. J Agric Food Chem 61, 98199827.
55Hobden, MR, Martin-Morales, A, Guerin-Deremaux, L, et al. (2013) In vitro fermentation of Nutriose® FB06, a wheat dextrin soluble fibre, in a continuous culture human colonic model system. PLOS ONE 8, e77128.
56Noack, J, Timm, D, Hospattankar, A, et al. (2013) Fermentation profiles of wheat dextrin, inulin and partially hydrolyzed guar gum using an in vitro digestion pretreatment and in vitro batch fermentation system model. Nutrients 5, 15001510.
57Wang, X & Gibson, GR (1993) Effects of the in vitro fermentation of oligofructose and inulin by bacteria growing in the human large intestine. J Appl Bacteriol 75, 373380.
58Morrison, DJ, Mackay, WG, Edwards, CA, et al. (2006) Butyrate production from oligofructose fermentation by the human faecal flora: what is the contribution of extracellular acetate and lactate? Br J Nutr 96, 570577.
59Lyra, A, Lahtinen, S, Tiihonen, K, et al. (2010) Intestinal microbiota and overweight. Benef Microbes 1, 407421.
60Ley, RE, Turnbaugh, PJ, Klein, S, et al. (2006) Microbial ecology: human gut microbes associated with obesity. Nature 444, 10221023.
61Turnbaugh, PJ, Ley, RE, Mahowald, MA, et al. (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 10271031.
62Payne, AN, Chassard, C, Zimmermann, M, et al. (2011) The metabolic activity of gut microbiota in obese children is increased compared with normal-weight children and exhibits more exhaustive substrate utilization. Nutr Diabetes 1, e12.
63Brinkworth, GD, Noakes, M, Clifton, PM, et al. (2009) Comparative effects of very low-carbohydrate, high-fat and high-carbohydrate, low-fat weight-loss diets on bowel habit and faecal short-chain fatty acids and bacterial populations. Br J Nutr 101, 14931502.
64Schwiertz, A, Taras, D, Schafer, K, et al. (2010) Microbiota and SCFA in lean and overweight healthy subjects. Obesity 18, 190195.
65Tims, S, Derom, C, Jonkers, DM, et al. (2013) Microbiota conservation and BMI signatures in adult monozygotic twins. ISME J 7, 707717.
66Le Chatelier, E, Nielsen, T, Qin, J, et al. (2013) Richness of human gut microbiome correlates with metabolic markers. Nature 500, 541546.
67Tiihonen, K, Ouwehand, AC & Rautonen, N (2010) Effect of overweight on gastrointestinal microbiology and immunology: correlation with blood biomarkers. Br J Nutr 103, 10701078.
68Fleissner, CK, Huebel, N, Abd El-Bary, MM, et al. (2010) Absence of intestinal microbiota does not protect mice from diet-induced obesity. Br J Nutr 104, 919929.
69Borthakur, A, Priyamvada, S, Kumar, A, et al. (2012) A novel nutrient sensing mechanism underlies substrate-induced regulation of monocarboxylate transporter-1. Am J Physiol Gastrointest Liver Physiol 303, G1126G1133.
70Goncalves, P, Catarino, T, Gregorio, I, et al. (2012) Inhibition of butyrate uptake by the primary bile salt chenodeoxycholic acid in intestinal epithelial cells. J Cell Biochem 113, 29372947.
71Parrett, AM, Edwards, CA & Lokerse, E (1997) Colonic fermentation capacity in vitro. Development during weaning in breast-fed infants is slower for complex carbohydrates than for sugars. Am J Clin Nutr 65, 927933.
72Sarbini, SR, Kolida, S, Gibson, GR, et al. (2013) In vitro fermentation of commercial α-gluco-oligosaccharide by faecal microbiota from lean and obese human subjects. Br J Nutr 109, 19801989.
73Cani, 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, 10911103.
74Geurts, L, Lazarevic, V, Derrien, M, et al. (2011) Altered gut microbiota and endocannabinoid system tone in obese and diabetic leptin-resistant mice: impact on apelin regulation in adipose tissue. Front Microbiol 2, 149.
75Geurts, 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, 317.
76de Goffau, MC, Fuentes, S, van den Bogert, B, et al. (2014) Aberrant gut microbiota composition at the onset of type 1 diabetes in young children. Diabetologia 57, 15691577.
77de Goffau, MC, Luopajarvi, K, Knip, M, et al. (2013) Fecal microbiota composition differs between children with β-cell autoimmunity and those without. Diabetes 62, 12381244.
78Brown, 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.
79Wang, W, Chen, L, Zhou, R, et al. (2014) Increased proportions of Bifidobacterium and the Lactobacillus group and loss of butyrate-producing bacteria in inflammatory bowel disease. J Clin Microbiol 52, 398406.
80Machiels, K, Joossens, M, Sabino, J, et al. (2014) A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut 63, 12751283.
81Huda-Faujan, N, Abdulamir, AS, Fatimah, AB, et al. (2010) The impact of the level of the intestinal short chain fatty acids in inflammatory bowel disease patients versus healthy subjects. Open Biochem J 4, 5358.
82Treem, WR, Ahsan, N, Shoup, M, et al. (1994) Fecal short-chain fatty acids in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 18, 159164.
83Tjellström, B, Högberg, L, Stenhammar, L, et al. (2012) Effect of exclusive enteral nutrition on gut microflora function in children with Crohn's disease. Scand J Gastroenterol 47, 14541459.
84Tjellström, B, Högberg, L, Stenhammar, L, et al. (2013) Faecal short-chain fatty acid pattern in childhood coeliac disease is normalised after more than one year's gluten-free diet. Microb Ecol Health Dis 2013, 24.
85Tjellström, B, Stenhammar, L, Högberg, L, et al. (2010) Screening-detected and symptomatic untreated celiac children show similar gut microflora-associated characteristics. Scand J Gastroenterol 45, 10591062.
86Tjellström, B, Stenhammar, L, Högberg, L, et al. (2005) Gut microflora associated characteristics in children with celiac disease. Am J Gastroenterol 100, 27842788.
87Bottcher, MF, Nordin, EK, Sandin, A, et al. (2000) Microflora-associated characteristics in faeces from allergic and nonallergic infants. Clin Exp Allergy 30, 15901596.
88Macfarlane, S & Macfarlane, GT (2003) Regulation of short-chain fatty acid production. Proc Nutr Soc 62, 6772.
89Mills, E & O'Neill, LA (2014) Succinate: a metabolic signal in inflammation. Trends Cell Biol 24, 313320.
90Tannahill, GM, Curtis, AM, Adamik, J, et al. (2013) Succinate is an inflammatory signal that induces IL-1β through HIF-1α. Nature 496, 238242.
91Ariake, K, Ohkusa, T, Sakurazawa, T, et al. (2000) Roles of mucosal bacteria and succinic acid in colitis caused by dextran sulfate sodium in mice. J Med Dent Sci 47, 233241.
92Shiomi, Y, Nishiumi, S, Ooi, M, et al. (2011) GCMS-based metabolomic study in mice with colitis induced by dextran sulfate sodium. Inflamm Bowel Dis 17, 22612274.
93Song, WB, Lv, YH, Zhang, ZS, et al. (2009) Soluble intercellular adhesion molecule-1, d-lactate and diamine oxidase in patients with inflammatory bowel disease. World J Gastroenterol 15, 39163919.
94Murray, MJ, Gonze, MD, Nowak, LR, et al. (1994) Serum d( − )-lactate levels as an aid to diagnosing acute intestinal ischemia. Am J Surg 167, 575578.
95Halperin, ML & Kamel, KS (1996) d-Lactic acidosis: turning sugar into acids in the gastrointestinal tract. Kidney Int 49, 18.
96Duzgun, AP, Bugdayci, G, Sayin, B, et al. (2007) Serum d-lactate: a useful diagnostic marker for acute appendicitis. Hepatogastroenterology 54, 14831486.
97Vernia, P, Caprilli, R, Latella, G, et al. (1988) Fecal lactate and ulcerative colitis. Gastroenterology 95, 15641568.
98Hove, H & Mortensen, PB (1995) Influence of intestinal inflammation (IBD) and small and large-bowel length on fecal short-chain fatty-acids and lactate. Dig Dis Sci 40, 13721380.
99Hove, H, Holtug, K, Jeppesen, PB, et al. (1995) Butyrate absorption and lactate secretion in ulcerative colitis. Dis Colon Rectum 38, 519525.
100Marquet, P, Duncan, SH, Chassard, C, et al. (2009) Lactate has the potential to promote hydrogen sulphide formation in the human colon. FEMS Microbiol Lett 299, 128134.
101Nyangale, EP, Mottram, DS & Gibson, GR (2012) Gut microbial activity, implications for health and disease: the potential role of metabolite analysis. J Proteome Res 11, 55735585.
102Windey, K, De Preter, V & Verbeke, K (2012) Relevance of protein fermentation to gut health. Mol Nutr Food Res 56, 184196.
103Windey, K, De Preter, V, Louat, T, et al. (2012) Modulation of protein fermentation does not affect fecal water toxicity: a randomized cross-over study in healthy subjects. PLOS ONE 7, e52387.
104Birkett, A, Muir, J, Phillips, J, et al. (1996) Resistant starch lowers fecal concentrations of ammonia and phenols in humans. Am J Clin Nutr 63, 766772.
105Smith, EA & Macfarlane, GT (1996) Enumeration of human colonic bacteria producing phenolic and indolic compounds: effects of pH, carbohydrate availability and retention time on dissimilatory aromatic amino acid metabolism. J Appl Bacteriol 81, 288302.
106Swanson, KS, Grieshop, CM, Flickinger, EA, et al. (2002) Fructooligosaccharides and lactobacillus acidophilus modify bowel function and protein catabolites excreted by healthy humans. J Nutr 132, 30423050.
107Damen, B, Cloetens, L, Broekaert, WF, et al. (2012) Consumption of breads containing in situ-produced arabinoxylan oligosaccharides alters gastrointestinal effects in healthy volunteers. J Nutr 142, 470477.
108Cloetens, L, Broekaert, WF, Delaedt, Y, et al. (2010) Tolerance of arabinoxylan-oligosaccharides and their prebiotic activity in healthy subjects: a randomised, placebo-controlled cross-over study. Br J Nutr 103, 703713.
109Lecerf, JM, Depeint, F, Clerc, E, et al. (2012) Xylo-oligosaccharide (XOS) in combination with inulin modulates both the intestinal environment and immune status in healthy subjects, while XOS alone only shows prebiotic properties. Br J Nutr 108, 18471858.
110Shinohara, K, Ohashi, Y, Kawasumi, K, et al. (2010) Effect of apple intake on fecal microbiota and metabolites in humans. Anaerobe 16, 510515.
111Boler, BM, Serao, MC, Bauer, LL, et al. (2011) Digestive physiological outcomes related to polydextrose and soluble maize fibre consumption by healthy adult men. Br J Nutr 106, 18641871.
112Wutzke, KD, Lotz, M & Zipprich, C (2010) The effect of pre- and probiotics on the colonic ammonia metabolism in humans as measured by lactose-[15N2]ureide. Eur J Clin Nutr 64, 12151221.
113Gostner, A, Blaut, M, Schäffer, V, et al. (2006) Effect of isomalt consumption on faecal microflora and colonic metabolism in healthy volunteers. Br J Nutr 95, 4050.
114Roediger, W & Babidge, W (1997) Human colonocyte detoxification. Gut 41, 731734.
115Collino, S, Montoliu, I, Martin, FPJ, et al. (2013) Metabolic signatures of extreme longevity in northern Italian centenarians reveal a complex remodeling of lipids, amino acids, and gut microbiota metabolism. PLOS ONE 8, e56564.
116Patney, NL, Mehrotra, MP, Khanna, HK, et al. (1976) Urinary indican excretion in cirrhosis of liver. J Assoc Physicians India 24, 291295.
117Patney, NL, Saxena, SK, Mehrotra, MP, et al. (1977) Urinary indican in diabetes mellitus. J Indian Med Assoc 68, 9497.
118Renwick, AG, Thakrar, A, Lawrie, CA, et al. (1988) Microbial amino-acid metabolites and bladder cancer: no evidence of promoting activity in man. Hum Toxicol 7, 267272.
119Adams, RF, Murray, KE & Earl, JW (1985) High levels of fecal para-cresol in a group of hyperactive children. Lancet ii, 13131313.
120Pedersen, G, Brynskov, J & Saermark, T (2002) Phenol toxicity and conjugation in human colonic epithelial cells. Scand J Gastroenterol 37, 7479.
121Mccall, IC, Betanzos, A, Weber, DA, et al. (2009) Effects of phenol on barrier function of a human intestinal epithelial cell line correlate with altered tight junction protein localization. Toxicol Appl Pharmacol 241, 6170.
122Hughes, R, Kurth, MJ, McGilligan, V, et al. (2008) Effect of colonic bacterial metabolites on Caco-2 cell paracellular permeability in vitro. Nutr Cancer 60, 259266.
123Meijers, BK, Van Kerckhoven, S, Verbeke, K, et al. (2009) The uremic retention solute p-cresyl sulfate and markers of endothelial damage. Am J Kidney Dis 54, 891901.
124Roe, DA (1971) Effects of methionine and inorganic sulfate on indole toxicity and indican excretion in rats. J Nutr 101, 645654.
125Smith, EA & Macfarlane, GT (1997) Dissimilatory amino acid metabolism in human colonic bacteria. Anaerobe 3, 327337.
126Wang, L, Christophersen, CT, Sorich, MJ, et al. (2012) Elevated fecal short chain fatty acid and ammonia concentrations in children with autism spectrum disorder. Dig Dis Sci 57, 20962102.
127Visek, WJ (1978) Diet and cell-growth modulation by ammonia. Am J Clin Nutr 31, S216S220.
128Blachier, F, Mariotti, F, Huneau, JF, et al. (2007) Effects of amino acid-derived luminal metabolites on the colonic epithelium and physiopathological consequences. Amino Acids 33, 547562.
129Macfarlane, GT, Gibson, GR & Cummings, JH (1992) Comparison of fermentation reactions in different regions of the human colon. J Appl Bacteriol 72, 5764.
130Florin, T, Neale, G, Gibson, GR, et al. (1991) Metabolism of dietary sulfate: absorption and excretion in humans. Gut 32, 766773.
131Magee, EA, Richardson, CJ, Hughes, R, et al. (2000) Contribution of dietary protein to sulfide production in the large intestine: an in vitro and a controlled feeding study in humans. Am J Clin Nutr 72, 14881494.
132Leschelle, X, Goubern, M, Andriamihaja, M, et al. (2005) Adaptative metabolic response of human colonic epithelial cells to the adverse effects of the luminal compound sulfide. Biochim Biophys Acta 1725, 201212.
133Medani, M, Collins, D, Docherty, NG, et al. (2011) Emerging role of hydrogen sulfide in colonic physiology and pathophysiology. Inflamm Bowel Dis 17, 16201625.
134Pitcher, MCL, Beatty, ER & Cummings, JH (2000) The contribution of sulphate reducing bacteria and 5-aminosalicylic acid to faecal sulphide in patients with ulcerative colitis. Gut 46, 6472.
135Levine, J, Ellis, CJ, Furne, JK, et al. (1998) Fecal hydrogen sulfide production in ulcerative colitis. Am J Gastroenterol 93, 8387.
136Moore, J, Babidge, W, Millard, S, et al. (1998) Colonic luminal hydrogen sulfide is not elevated in ulcerative colitis. Dig Dis Sci 43, 162165.
137De Preter, V, Arijs, I, Windey, K, et al. (2012) Decreased mucosal sulfide detoxification is related to an impaired butyrate oxidation in ulcerative colitis. Inflamm Bowel Dis 18, 23712380.
138Jowett, SL, Seal, CJ, Pearce, MS, et al. (2004) Influence of dietary factors on the clinical course of ulcerative colitis: a prospective cohort study. Gut 53, 14791484.
139Deplancke, B & Gaskins, HR (2003) Hydrogen sulfide induces serum-independent cell cycle entry in nontransformed rat intestinal epithelial cells. FASEB J 17, 13101312.
140Attene-Ramos, MS, Wagner, ED & Plewa, MJ (2006) Evidence that hydrogen sulfide is a genotoxic agent. Mol Cancer Res 4, 914.
141Attene-Ramos, MS, Wagner, ED, Gaskins, HR, et al. (2007) Hydrogen sulfide induces direct radical-associated DNA damage. Mol Cancer Res 5, 455459.
142Attene-Ramos, MS, Nava, GM, Muellner, MG, et al. (2010) DNA damage and toxicogenomic analyses of hydrogen sulfide in human intestinal epithelial FHs 74 Int cells. Environ Mol Mutagen 51, 304314.
143Koehne, CH & Dubois, RN (2004) Cox-2 inhibition and colorectal cancer. Semin Oncol 31, 1221.
144Blachier, F, Davila, AM, Mimoun, S, et al. (2010) Luminal sulfide and large intestine mucosa: friend or foe? Amino Acids 39, 335347.
145Mortensen, PB & Clausen, MR (1996) Short-chain fatty acids in the human colon: relation to gastrointestinal health and disease. Scand J Gastroenterol 31, 132148.
146Makelainen, HS, Makivuokko, HA, Salminen, SJ, et al. (2007) The effects of polydextrose and xylitol on microbial community and activity in a 4-stage colon simulator. J Food Sci 72, M153M159.
147Alles, MS, Katan, MB, Salemans, JMJI, et al. (1997) Bacterial fermentation of fructooligosaccharides and resistant starch in patients with an ileal pouch anal anastomosis. Am J Clin Nutr 66, 12861292.
148Sakurazawa, T & Ohkusa, T (2005) Cytotoxicity of organic acids produced by anaerobic intestinal bacteria on cultured epithelial cells. J Gastroenterol 40, 600609.
149Kim, E, Coelho, D & Blachier, F (2013) Review of the association between meat consumption and risk of colorectal cancer. Nutr Res 33, 983994.
150Del Rio, D, Rodriguez-Mateos, A, Spencer, JPE, et al. (2013) Dietary (poly)phenolics in human health: structures, bioavailability, and evidence of protective effects against chronic diseases. Antioxid Redox Signal 18, 18181892.
151Dall'Asta, M, Calani, L, Tedeschi, M, et al. (2012) Identification of microbial metabolites derived from in vitro fecal fermentation of different polyphenolic food sources. Nutrition 28, 197203.
152Bolca, S, Van de Wiele, T & Possemiers, S (2013) Gut metabotypes govern health effects of dietary polyphenols. Curr Opin Biotechnol 24, 220225.
153Tzounis, X, Rodriguez-Mateos, A, Vulevic, J, et al. (2011) Prebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomized, controlled, double-blind, crossover intervention study. Am J Clin Nutr 93, 6272.
154Jaganath, IB, Mullen, W, Lean, ME, et al. (2009) In vitro catabolism of rutin by human fecal bacteria and the antioxidant capacity of its catabolites. Free Radic Biol Med 47, 11801189.
155Tuohy, KM, Conterno, L, Gasperotti, M, et al. (2012) Up-regulating the human intestinal microbiome using whole plant foods, polyphenols, and/or fiber. J Agric Food Chem 60, 87768782.
156Moco, S, Martin, FPJ & Rezzi, S (2012) Metabolomics view on gut microbiome modulation by polyphenol-rich foods. J Proteome Res 11, 47814790.
157Asano, 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.
158Foster, JA & McVey Neufeld, K-A (2013) Gut-brain axis: how the microbiome influences anxiety and depression. Trends Neurosci 36, 305312.
159Rhee, SH, Pothoulakis, C & Mayer, EA (2009) Principles and clinical implications of the brain-gut-enteric microbiota axis. Nat Rev Gastroenterol Hepatol 6, 306314.
160Gin, H, Rigalleau, V, Caubet, O, et al. (1999) Effects of red wine, tannic acid, or ethanol on glucose tolerance in non-insulin-dependent diabetic patients and on starch digestibility in vitro. Metabolism 48, 11791183.
161Henry, CJ, Lightowler, HJ, Newens, KJ, et al. (2008) The influence of adding fats of varying saturation on the glycaemic response of white bread. Int J Food Sci Nutr 59, 6169.
162Bazzocco, S, Mattila, I, Guyot, S, et al. (2008) Factors affecting the conversion of apple polyphenols to phenolic acids and fruit matrix to short-chain fatty acids by human faecal microbiota in vitro. Eur J Nutr 47, 442452.
163Fallani, 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.
164Zoetendal, EG, Rajilic-Stojanovic, M & De Vos, WM (2008) High-throughput diversity and functionality analysis of the gastrointestinal tract microbiota. Gut 57, 16051615.
165Albenberg, L & Wu, GD (2014) Diet and the intestinal microbiome: associations, functions, and implications for health and disease. Gastroenterology 146, 15641572.
166Yap, IKS, Brown, IJ, Chan, Q, et al. (2010) Metabolome-wide association study identifies multiple biomarkers that discriminate north and south Chinese populations at differing risks of cardiovascular disease: INTERMAP study. J Proteome Res 9, 66476654.
167Ou, JH, Delany, JP, Zhang, M, et al. (2012) Association between low colonic short-chain fatty acids and high bile acids in high colon cancer risk populations. Nutr Cancer 64, 3440.
168Macfarlane, GT & Macfarlane, S (2011) Fermentation in the human large intestine: its physiologic consequences and the potential contribution of prebiotics. J Clin Gastroenterol 45, suppl., S120S127.
169Cummings, JH, Hill, MJ, Bone, ES, et al. (1979) Effect of meat protein and dietary fiber on colonic function and metabolism. II. Bacterial metabolites in feces and urine. Am J Clin Nutr 32, 20942101.
170Stephen, AM, Wiggins, HS & Cummings, JH (1987) Effect of changing transit-time on colonic microbial-metabolism in man. Gut 28, 601609.
171El Oufir, L, Barry, JL, Flourie, B, et al. (2000) Relationships between transit time in man and in vitro fermentation of dietary fiber by fecal bacteria. Eur J Clin Nutr 54, 603609.
172Govers, MJ, Gannon, NJ, Dunshea, FR, et al. (1999) Wheat bran affects the site of fermentation of resistant starch and luminal indexes related to colon cancer risk: a study in pigs. Gut 45, 840847.
173Morita, T, Kasaoka, S, Hase, K, et al. (1999) Psyllium shifts the fermentation site of high-amylose cornstarch toward the distal colon and increases fecal butyrate concentration in rats. J Nutr 129, 20812087.
174Zhao, Y, Wu, J, Li, JV, et al. (2013) Gut microbiota composition modifies fecal metabolic profiles in mice. J Proteome Res 12, 29872999.
175Washington, N, Harris, M, Mussellwhite, A, et al. (1998) Moderation of lactulose-induced diarrhea by psyllium: effects on motility and fermentation. Am J Clin Nutr 67, 317321.
176Cherbut, C (2003) Motor effects of short-chain fatty acids and lactate in the gastrointestinal tract. Proc Nutr Soc 62, 9599.
177Kamath, PS, Phillips, SF, O'Connor, MK, et al. (1990) Colonic capacitance and transit in man: modulation by luminal contents and drugs. Gut 31, 443449.
178Jouet, P, Moussata, D, Duboc, H, et al. (2013) Effect of short-chain fatty acids and acidification on the phasic and tonic motor activity of the human colon. Neurogastroenterol Motil 25, 943949.
179Dougal, K, Harris, PA, Edwards, A, et al. (2012) A comparison of the microbiome and the metabolome of different regions of the equine hindgut. FEMS Microbiol Ecol 82, 642652.
180Wikoff, 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.
181Verbeke, K, Ferchaud-Roucher, V, Preston, T, et al. (2010) Influence of the type of indigestible carbohydrate on plasma and urine short-chain fatty acid profiles in healthy human volunteers. Eur J Clin Nutr 64, 678684.
182de Graaf, AA & Venema, K (2007) Gaining insight into microbial physiology in the large intestine: a special role for stable isotopes. Adv Microb Physiol 53, 73168, 313–314.
183Osswald, K, Becker, TW, Grimm, M, et al. (2000) Inter- and intra-individual variation of faecal water - genotoxicity in human colon cells. Mutat Res 472, 5970.
184Bosworth, D & Venitt, S (1986) Testing human fecal extracts for genotoxic activity with the SOS chromotest: the importance of controlling for fecal enzyme activity. Mutagenesis 1, 143149.
185De Kok, TMCM & van Maanen, JMS (2000) Evaluation of fecal mutagenicity and colorectal cancer risk. Mutat Res 463, 53101.
186Mower, HF, Ichinotsubo, D, Wang, LW, et al. (1982) Fecal mutagens in two Japanese populations with different colon cancer risks. Cancer Res 42, 11641169.
187Gratz, SW, Wallace, RJ & El-Nezami, HS (2011) Recent perspectives on the relations between fecal mutagenicity, genotoxicity and diet. Front Pharmacol 2, 4.
188Klinder, A, Karlsson, PC, Clune, Y, et al. (2007) Fecal water as a non-invasive biomarker in nutritional intervention: comparison of preparation methods and refinement of different endpoints. Nutr Cancer 57, 158167.
189Karlsson, PC, Huss, U, Jenner, A, et al. (2005) Human fecal water inhibits COX-2 in colonic HT-29 cells: role of phenolic compounds. J Nutr 135, 23432349.
190Nordling, MM, Glinghammar, B, Karlsson, PC, et al. (2003) Effects on cell proliferation, activator protein-1 and genotoxicity by fecal water from patients with colorectal adenomas. Scand J Gastroenterol 38, 549555.
191Morrow, DMP, Ryan, MP & McGlynn, H (1996) An in vitro model to assess tumour promotor activity. Br J Cancer 74, 68.
192Gill, CIR, McDougall, GJ, Glidewell, S, et al. (2010) Profiling of phenols in human fecal water after raspberry supplementation. J Agric Food Chem 58, 1038910395.
193Jovov, B, Wills, NK & Lewis, SAA (1991) spectroscopic method for assessing confluence of epithelial-cell cultures. Am J Physiol 261, C1196C1203.
194Ramakers, JD, Volman, JJ, Biorklund, M, et al. (2007) Fecal water from ileostomic patients consuming oat β-glucan enhances immune responses in enterocytes. Mol Nutr Food Res 51, 211220.
195Lapre, JA & VanderMeer, R (1992) Diet-induced increase of colonic bile-acids stimulates lytic activity of fecal water and proliferation of colonic cells. Carcinogenesis 13, 4144.
196Haza, AI, Glinghammar, B, Grandien, A, et al. (2000) Effect of colonic luminal components on induction of apoptosis in human colonic cell lines. Nutr Cancer 36, 7989.
197Glinghammar, B, Holmberg, K & Rafter, J (1999) Effects of colonic lumenal components on AP-1-dependent gene transcription in cultured human colon carcinoma cells. Carcinogenesis 20, 969976.
198Glinghammar, B & Rafter, J (2001) Colonic luminal contents induce cyclooxygenase 2 transcription in human colon carcinoma cells. Gastroenterology 120, 401410.
199Zeng, HW & Davis, CD (2003) Down-regulation of proliferating cell nuclear antigen gene expression occurs during cell cycle arrest induced by human fecal water in colonic HT-29 cells. J Nutr 133, 26822687.
200Pool-Zobel, BL (2005) Inulin-type fructans and reduction in colon cancer risk: review of experimental and human data. Br J Nutr 93, S73S90.
201Klinder, A, Forster, A, Caderni, G, et al. (2004) Fecal water genotoxicity is predictive of tumor-preventive activities by inulin-like oligofructoses, probiotics (Lactobacillus rhamnosus and Bifidobacterium lactis), and their synbiotic combination. Nutr Cancer 49, 144155.
202Glei, M, Habermann, N, Osswald, K, et al. (2005) Assessment of DNA damage and its modulation by dietary and genetic factors in smokers using the comet assay: a biomarker model. Biomarkers 10, 203217.
203Wu, WT, Cheng, HC & Chen, HL (2011) Ameliorative effects of konjac glucomannan on human faecal β-glucuronidase activity, secondary bile acid levels and faecal water toxicity towards Caco-2 cells. Br J Nutr 105, 593600.
204Walton, GE, van den Heuvel, EGHM, Kosters, MHW, et al. (2012) A randomised crossover study investigating the effects of galacto-oligosaccharides on the faecal microbiota in men and women over 50 years of age. Br J Nutr 107, 14661475.
205Le Gall, G, Noor, SO, Ridgway, K, et al. (2011) Metabolomics of fecal extracts detects altered metabolic activity of gut microbiota in ulcerative colitis and irritable bowel syndrome. J Proteome Res 10, 42084218.
206Martin, FPJ, Collino, S & Rezzi, S (2011) 1H NMR-based metabonomic applications to decipher gut microbial metabolic influence on mammalian health. Magn Reson Chem 49, Suppl. S1, S47S54.
207Martin, FPJ, Rezzi, S, Pere-Trepat, E, et al. (2009) Metabolic effects of dark chocolate consumption on energy, gut microbiota, and stress-related metabolism in free-living subjects. J Proteome Res 8, 55685579.
208Cheng, Y, Xie, GX, Chen, TL, et al. (2012) Distinct urinary metabolic profile of human colorectal cancer. J Proteome Res 11, 13541363.
209Qiu, YP, Cai, GX, Su, MM, et al. (2010) Urinary metabonomic study on colorectal cancer. J Proteome Res 9, 16271634.
210Qiu, Y, Cai, G, Su, M, et al. (2009) Serum metabolite profiling of human colorectal cancer using GC-TOFMS and UPLC-QTOFMS. J Proteome Res 8, 48444850.
211Tulipani, S, Llorach, R, Jauregui, O, et al. (2011) Metabolomics unveils urinary changes in subjects with metabolic syndrome following 12-week nut consumption. J Proteome Res 10, 50475058.
212Calvani, R, Miccheli, A, Capuani, G, et al. (2010) Gut microbiome-derived metabolites characterize a peculiar obese urinary metabotype. Int J Obes 34, 10951098.
213Suhre, K, Meisinger, C, Doring, A, et al. (2010) Metabolic footprint of diabetes: a multiplatform metabolomics study in an epidemiological setting. PLoS ONE 5, e13953.
214Ponnusamy, K, Choi, JN, Kim, J, et al. (2011) Microbial community and metabolomic comparison of irritable bowel syndrome faeces. J Med Microbiol 60, 817827.
215Ktsoyan, ZA, Beloborodova, NV, Sedrakyan, AM, et al. (2011) Profiles of microbial fatty acids in the human metabolome are disease-specific. Front Microbiol 1, 148.
216Martin, FPJ, Sprenger, N, Montoliu, I, et al. (2010) Dietary modulation of gut functional ecology studied by fecal metabonomics. J Proteome Res 9, 52845295.
217Fava, F, Gitau, R, Griffin, BA, et al. (2013) The type and quantity of dietary fat and carbohydrate alter faecal microbiome and short-chain fatty acid excretion in a metabolic syndrome ‘at-risk’ population. Int J Obes 37, 216223.
218Seiber, JN, Molyneux, RJ & Schieberle, P (2014) Targeted metabolomics: a new section in the Journal of Agricultural and Food Chemistry. J Agric Food Chem 62, 2223.
219Martin, FPJ, Sprenger, N, Yap, IKS, et al. (2009) Panorganismal gut microbiome-host metabolic crosstalk. J Proteome Res 8, 20902105.
220Ndagijimana, M, Laghi, L, Vitali, B, et al. (2009) Effect of a synbiotic food consumption on human gut metabolic profiles evaluated by 1H nuclear magnetic resonance spectroscopy. Int J Food Microbiol 134, 147153.
221Vitali, B, Ndagijimana, M, Cruciani, F, et al. (2010) Impact of a synbiotic food on the gut microbial ecology and metabolic profiles. BMC Microbiol 10, 4.
222De Preter, V, Ghebretinsae, AH, Abrahantes, JC, et al. (2011) Impact of the synbiotic combination of Lactobacillus casei Shirota and oligofructose-enriched inulin on the fecal volatile metabolite profile in healthy subjects. Mol Nutr Food Res 55, 714722.
223De Preter, V, Joossens, M, Ballet, V, et al. (2013) Metabolic profiling of the impact of oligofructose-enriched inulin in Crohn's disease patients: a double-blinded randomized controlled trial. Clin Transl Gastroenterol 4, e30.
224Zoetendal, 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, 14151426.
225Faust, K & Raes, J (2012) Microbial interactions: from networks to models. Nat Rev Microbiol 10, 538550.
226Bron, PA, van Baarlen, P & Kleerebezem, M (2012) Emerging molecular insights into the interaction between probiotics and the host intestinal mucosa. Nat Rev Microbiol 10, 6678.
227Arumugam, M, Raes, J, Pelletier, E, et al. (2011) Enterotypes of the human gut microbiome. Nature 473, 174180.
228De Filippo, C, Cavalieri, D, Di Paola, M, et al. (2010) Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci U S A 107, 1469114696.
229Guerin-Danan, C, Andrieux, C, Popot, F, et al. (1997) Pattern of metabolism and composition of the fecal microflora in infants 10 to 18 months old from day care centers. J Pediatr Gastroenterol Nutr 25, 281289.
230Siigur, U, Ormisson, A & Tamm, A (1993) Faecal short-chain fatty acids in breast-fed and bottle-fed infants. Acta Paediatr 82, 536538.
231Holscher, HD, Faust, KL, Czerkies, LA, et al. (2012) Effects of prebiotic-containing infant formula on gastrointestinal tolerance and fecal microbiota in a randomized controlled trial. JPEN J Parenter Enteral Nutr 36, 95S105S.
232Norin, E, Midtvedt, T & Bjorksten, B (2004) Development of faecal short-chain fatty acid pattern during the first year of life in Estonian and Swedish infants. Microb Ecol Health Dis 16, 812.
233Bakker-Zierikzee, AM, Alles, MS, Knol, J, et al. (2005) Effects of infant formula containing a mixture of galacto- and fructo-oligosaccharides or viable Bifidobacterium animalis on the intestinal microflora during the first 4 months of life. Br J Nutr 94, 783790.
234Samuelsson, U & Ludvigsson, J (2004) The concentrations of short-chain fatty acids and other microflora-associated characteristics in faeces from children with newly diagnosed type 1 diabetes and control children and their family members. Diabet Med 21, 6467.
235Parrett, AM & Edwards, CA (1997) In vitro fermentation of carbohydrate by breast fed and formula fed infants. Arch Dis Child 76, 249253.
236Whelan, K, Judd, PA, Preedy, VR, et al. (2005) Fructooligosaccharides and fiber partially prevent the alterations in fecal microbiota and short-chain fatty acid concentrations caused by standard enteral formula in healthy humans. J Nutr 135, 18961902.
237Lewis, SJ & Heaton, KW (1997) Increasing butyrate concentration in the distal colon by accelerating intestinal transit. Gut 41, 245251.
238Reimer, RA, Pelletier, X, Carabin, IG, et al. (2012) Faecal short chain fatty acids in healthy subjects participating in a randomised controlled trial examining a soluble highly viscous polysaccharide versus control. J Hum Nutr Diet 25, 373377.
239Fernando, WMU, Hill, JE, Zello, GA, et al. (2010) Diets supplemented with chickpea or its main oligosaccharide component raffinose modify faecal microbial composition in healthy adults. Beneficial Microbes 1, 197207.
240McOrist, AL, Miller, RB, Bird, AR, et al. (2011) Fecal butyrate levels vary widely among individuals but are usually increased by a diet high in resistant starch. J Nutr 141, 883889.
241Nemoto, H, Kataoka, K, Ishikawa, H, et al. (2012) Reduced diversity and imbalance of fecal microbiota in patients with ulcerative colitis. Dig Dis Sci 57, 29552964.
242McOrist, AL, Abell, GC, Cooke, C, et al. (2008) Bacterial population dynamics and faecal short-chain fatty acid (SCFA) concentrations in healthy humans. Br J Nutr 100, 138146.
243Hylla, S, Gostner, A, Dusel, G, et al. (1998) Effects of resistant starch on the colon in healthy volunteers: possible implications for cancer prevention. Am J Clin Nutr 67, 136142.
244Benassi-Evans, B, Clifton, P, Noakes, M, et al. (2010) High-protein/high red meat and high-carbohydrate weight-loss diets do not differ in their effect on faecal water genotoxicity tested by use of the WIL2-NS cell line and with other biomarkers of bowel health. Mutat Res 703, 130136.
245Ling, WH & Hanninen, O (1992) Shifting from a conventional diet to an uncooked vegan diet reversibly alters fecal hydrolytic activities in humans. J Nutr 122, 924930.
246Patel, KP, Luo, FJG, Plummer, NS, et al. (2012) The production of p-cresol sulfate and indoxyl sulfate in vegetarians versus omnivores. Clin J Am Soc Nephrol 7, 982988.
247De Preter, V, Geboes, K, Verbrugghe, K, et al. (2004) The in vivo use of the stable isotope-labelled biomarkers lactose-[15N]ureide and [2H4]tyrosine to assess the effects of pro- and prebiotics on the intestinal flora of healthy human volunteers. Br J Nutr 92, 439446.
248De Preter, V, Coopmans, T, Rutgeerts, P, et al. (2007) Influence of long-term administration of lactulose and Saccharomyces boulardii on the colonic generation of phenolic compounds and on different gastro-intestinal parameters. J Am Coll Nutr 25, 541549.
249De Preter, V, Vanhoutte, T, Huys, G, et al. (2007) Effects of Lactobacillus casei Shirota, Bifidobacterium breve, and oligofructose-enriched inulin on colonic nitrogen-protein metabolism in healthy humans. Am J Physiol Gastrointest Liver Physiol 292, G358G368.
250Cloetens, L, De Preter, V, Swennen, K, et al. (2008) Dose-response effect of arabinoxylooligosaccharides on gastrointestinal motility and on colonic bacterial metabolism in healthy volunteers. J Am Coll Nutr 27, 512518.
251Heavey, PM, Savage, SAH, Parrett, A, et al. (2003) Protein-degradation products and bacterial enzyme activities in faeces of breast-fed and formula-fed infants. Br J Nutr 89, 509515.
252Clarke, JM, Topping, DL, Christophersen, CT, et al. (2011) Butyrate esterified to starch is released in the human gastrointestinal tract. Am J Clin Nutr 94, 12761283.
253Bianchi, MA, Scazzina, F, Del Rio, D, et al. (2010) Ability of a high-total antioxidant capacity diet to increase stool weight and bowel antioxidant status in human subjects. Br J Nutr 104, 15001507.
254Alakomi, HL, Puupponen-Pimia, R, Aura, AM, et al. (2007) Weakening of Salmonella with selected microbial metabolites of berry-derived phenolic compounds and organic acids. J Agric Food Chem 55, 39053912.
255Ko, HS, Jin, RD, Krishnan, HB, et al. (2009) Biocontrol ability of Lysobacter antibioticus HS124 against phytophthora blight is mediated by the production of 4-hydroxyphenylacetic acid and several lytic enzymes. Curr Microbiol 59, 608615.
256Roowi, S, Stalmach, A, Mullen, W, et al. (2010) Green tea flavan-3-ols: colonic degradation and urinary excretion of catabolites by humans. J Agric Food Chem 58, 12961304.
257Okello, EJ, Leylabi, R & McDougall, GJ (2012) Inhibition of acetylcholinesterase by green and white tea and their simulated intestinal metabolites. Food Funct 3, 651661.
258Ni, N, Choudhary, G, Li, M, et al. (2008) Pyrogallol and its analogs can antagonize bacterial quorum sensing in Vibrio harveyi. Bioorg Med Chem Lett 18, 15671572.
259Taguri, T, Tanaka, T & Kouno, I (2006) Antibacterial spectrum of plant polyphenols and extracts depending upon hydroxyphenyl structure. Biol Pharm Bull 29, 22262235.
260Jackman, KA, Woodman, OL & Sobey, CG (2007) Isoflavones, equol and cardiovascular disease: pharmacological and therapeutic insights. Curr Med Chem 14, 28242830.
261Ishimi, Y (2009) Soybean isoflavones in bone health. Forum Nutr 61, 104116.
262Davis, CD & Milner, JA (2009) Gastrointestinal microflora, food components and colon cancer prevention. J Nutr Biochem 20, 743752.
263Selma, MV, Espin, JC & Tomas-Barberan, FA (2009) Interaction between phenolics and gut microbiota: role in human health. J Agric Food Chem 57, 64856501.
264Larrosa, M, Gonzalez-Sarrias, A, Garcia-Conesa, MT, et al. (2006) Urolithins, ellagic acid-derived metabolites produced by human colonic microflora, exhibit estrogenic and antiestrogenic activities. J Agric Food Chem 54, 16111620.
265Del Rio, D, Borges, G & Crozier, A (2010) Berry flavonoids and phenolics: bioavailability and evidence of protective effects. Br J Nutr 104, S67S90.
266Dell'Agli, M, Galli, GV, Bulgari, M, et al. (2010) Ellagitannins of the fruit rind of pomegranate (Punica granatum) antagonize in vitro the host inflammatory response mechanisms involved in the onset of malaria. Malar J 9, 208.
267Cervantes-Laurean, D, Schramm, DD, Jacobson, EL, et al. (2006) Inhibition of advanced glycation end product formation on collagen by rutin and its metabolites. J Nutr Biochem 17, 531540.

Keywords

Metrics

Altmetric attention score

Full text views