Impact of Diet-Modulated Butyrate Production on Intestinal Barrier Function and Inflammation

Knud Erik Bach Knudsen, Helle Nygaard Lærke, Mette Skou Hedemann, Tina Skau Nielsen, Anne Krog Ingerslev, Ditte Søvsø Gundelund Nielsen, Peter Kappel Theil, Stig Purup, Stine Hald, Anne Grethe Schioldan, Maria L Marco, Søren Gregersen, Kjeld Hermansen, Knud Erik Bach Knudsen, Helle Nygaard Lærke, Mette Skou Hedemann, Tina Skau Nielsen, Anne Krog Ingerslev, Ditte Søvsø Gundelund Nielsen, Peter Kappel Theil, Stig Purup, Stine Hald, Anne Grethe Schioldan, Maria L Marco, Søren Gregersen, Kjeld Hermansen

Abstract

A major challenge in affluent societies is the increase in disorders related to gut and metabolic health. Chronic over nutrition by unhealthy foods high in energy, fat, and sugar, and low in dietary fibre is a key environmental factor responsible for this development, which may cause local and systemic inflammation. A low intake of dietary fibre is a limiting factor for maintaining a viable and diverse microbiota and production of short-chain fatty acids in the gut. A suppressed production of butyrate is crucial, as this short-chain fatty acid (SCFA) can play a key role not only in colonic health and function but also at the systemic level. At both sites, the mode of action is through mediation of signalling pathways involving nuclear NF-κB and inhibition of histone deacetylase. The intake and composition of dietary fibre modulate production of butyrate in the large intestine. While butyrate production is easily adjustable it is more variable how it influences gut barrier function and inflammatory markers in the gut and periphery. The effect of butyrate seems generally to be more consistent and positive on inflammatory markers related to the gut than on inflammatory markers in the peripheral tissue. This discrepancy may be explained by differences in butyrate concentrations in the gut compared with the much lower concentration at more remote sites.

Keywords: butyrate; dietary fibre; gut barrier function; gut inflammation; systemic inflammation.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Butyrate formation from dietary fibre and absorption in the large intestine. Two pathways of butyrate production from butyryl-CoA in bacteria has been reported. Letter “A” indicates that butyryl-CoA is phosphorylated to butyryl-phosphate and converted to butyrate via butyrate kinase. Letter “B” shows that the CoA moiety of butyryl-CoA is transferred to external acetate via butyryl-CoA: acetate transferase, leading to the formation of butyrate and acetyl-CoA [38]. Several receptors for butyrate including G-protein-coupled receptors 41 (GPR41), GPR43 and GPR109A have been identified. GPR41 is found in adipose tissues and immune cells, GPR43 in immune cells whereas GPR109A is present in colonic cells. GPR109A is essential for butyrate-mediated induction of IL-18 in colonic epithelium. Modified from [27].
Figure 2
Figure 2
Absorption of butyrate (nC4) in the large intestine. Butyrate transport with monocarboxylate transporters (MCT) is saturable and coupled with H+ transport. Several G-protein-coupled (GPR) receptors for butyrate have been identified and detected in various tissues including the colonic epithelium (GPR109A) and immune cells (GPR41 and GPR43). SMCT, Na-coupled monocarboxylate transport. Modified from [54].
Figure 3
Figure 3
NF-κB central role in inflammation. Several pro-inflammatory signals such as cytokines, protein kinase C (PKC) activators, infectious agents or oxidative stress activates NF-κB. In response to these signals, NF-κB controls the expression of many mediators of the inflammatory reaction: cytokines, chemokines, enzymes and adhesion molecules. Modified from [84].
Figure 4
Figure 4
Schematic representation of the interaction between adipocytes and macrophages showing some of the molecules released. Expansion of adipose tissue during weight gain leads to the recruitment of macrophages through various signals (e.g. chemokines such as chemokine (C-C motif) ligand 2 (CCL2) released by adipocytes. Macrophages accumulate around apoptotic adipocytes. Mediators synthesized by adipocytes and resident macrophages contribute to local and systemic inflammation. Reproduced from [6].

References

    1. Cornier M.A., Dabelea D., Hernandez T.L., Lindstrom R.C., Steig A.J., Stob N.R., Van Pelt R.E., Wang H., Eckel R.H. The metabolic syndrome. Endocr. Rev. 2008;29:777–822. doi: 10.1210/er.2008-0024.
    1. Lovre D., Mauvais-Jarvis F. Trends in prevalence of the metabolic syndrome. JAMA. 2015;314:950–951. doi: 10.1001/jama.2015.8625.
    1. Bray G.A., Nielsen S.J., Popkin B.M. Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity. Am. J. Clin. Nutr. 2004;79:537–543. doi: 10.1093/ajcn/79.4.537.
    1. Stanhope K.L. Role of fructose-containing sugars in the epidemics of obesity and metabolic syndrome. Annl. Rev. Med. 2012;63:329–343. doi: 10.1146/annurev-med-042010-113026.
    1. Calder P.C., Ahluwalia N., Brouns F., Buetler T., Clement K., Cunningham K., Esposito K., Jönsson L.S., Kolb H., Lansink M., et al. Dietary factors and low-grade inflammation in relation to overweight and obesity. Br. J. Nutr. 2011;106:S1–S78. doi: 10.1017/S0007114511005460.
    1. Tilg H., Moschen A.R. Adipocytokines: Mediators linking adipose tissue, inflammation and immunity. Nature. Rev. Immunol. 2006;6:772–783. doi: 10.1038/nri1937.
    1. Minihane A.M., Vinoy S., Russell W.R., Baka A., Roche H.M., Tuohy K.M., Teeling J.L., Blaak E.E., Fenech M., Vauzour D., et al. Low-grade inflammation, diet composition and health: Current research evidence and its translation. Br. J. Nutr. 2015;114:999–1012. doi: 10.1017/S0007114515002093.
    1. Maachi M., Pieroni L., Bruckert E., Jardel C., Fellahi S., Hainque B., Capeau J., Bastard J. Systemic low-grade inflammation is related to both circulating and adipose tissue TNFα, leptin and IL-6 levels in obese women. Int. J. Obes. 2004;28:993–997. doi: 10.1038/sj.ijo.0802718.
    1. Hamer H.M., Jonkers D., Venema K., Vanhoutvin S., Troost F.J., Brummer R.J. Review article: The role of butyrate on colonic function. Alim. Pharma. Ther. 2008;27:104–119. doi: 10.1111/j.1365-2036.2007.03562.x.
    1. Leonel A.J., Alvarez-Leite J.I. Butyrate: Implications for intestinal function. Curr. Opin. Clin. Nutr. Met. Care. 2012;15:474–479. doi: 10.1097/MCO.0b013e32835665fa.
    1. Fung K.Y., Cosgrove L., Lockett T., Head R., Topping D.L. A review of the potential mechanisms for the lowering of colorectal oncogenesis by butyrate. Br. J. Nutr. 2012;108:820–831. doi: 10.1017/S0007114512001948.
    1. Bach Knudsen K.E. Effect of dietary non-digestible carbohydrates on the rate of SCFA delivery peripheral tissues. FFI J. Jpn. 2005;210:1008–1017.
    1. Flint H.J. The impact of nutrition on the human microbiome. Nutr. Rev. 2012;70:S10–S13. doi: 10.1111/j.1753-4887.2012.00499.x.
    1. Flint H.J., Scott K.P., Louis P., Duncan S.H. The role of the gut microbiota in nutrition and health. Nature Rev. Gastro. Hepatol. 2012;9:577–589. doi: 10.1038/nrgastro.2012.156.
    1. Koh A., De Vadder F., Kovatcheva-Datchary P., Bäckhed F. From dietary fiber to host physiology: Short-chain fatty acids as key bacterial metabolites. Cell. 2016;165:1332–1345. doi: 10.1016/j.cell.2016.05.041.
    1. Rowland I., Gibson G., Heinken A., Scott K., Swann J., Thiele I., Tuohy K. Gut microbiota functions: Metabolism of nutrients and other food components. Eur. J. Nutr. 2017:1–24. doi: 10.1007/s00394-017-1445-8.
    1. Bergman E.N. Energy contributions of volatile fatty acids from the gastrointestinal tract in various species. Phys. Rev. 1990;70:567–590. doi: 10.1152/physrev.1990.70.2.567.
    1. Cummings J.H., Pomare E.W., Branch W.J., Naylor C.P.E., Macfarlane G.T. Short-chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut. 1987;28:1221–1227. doi: 10.1136/gut.28.10.1221.
    1. Ingerslev A.K., Theil P.K., Hedemann M.S., Lærke H.N., Bach Knudsen K.E. Resistant starch and arabinoxylan augment SCFA absorption, but affect postprandial glucose and insulin responses differently. Br. J. Nutr. 2014;111:1564–1576. doi: 10.1017/S0007114513004066.
    1. Roediger W.E.W. The starved colon-diminished mucosa nutrition, diminished absorption, and colitis. Dis Colon Rectum. 1990;33:858–862. doi: 10.1007/BF02051922.
    1. Chen J., Vitetta L. Inflammation-modulating effect of butyrate in the prevention of colon cancer by dietary fiber. Clin. Colorectal Cancer. 2018;17:e541–e544. doi: 10.1016/j.clcc.2018.05.001.
    1. Guilloteau P., Martin L., Eeckhaut V., Ducatelle R., Zabielski R., Van Immerseel F. From the gut to the peripheral tissues: The multiple effects of butyrate. Nutr. Res. Rev. 2010;23:366–384. doi: 10.1017/S0954422410000247.
    1. Perego S., Sansoni V., Banfi G., Lombardi G. Sodium butyrate has anti-proliferative, pro-differentiating, and immunomodulatory effects in osteosarcoma cells and counteracts the tnfalpha-induced low-grade inflammation. Int J. Immunopathol. Pharmacol. 2018;32:1–14. doi: 10.1177/0394632017752240.
    1. Clarke J.M., Young G.P., Topping D.L., Bird A.R., Cobiac L., Scherer B.L., Winkler J.G., Lockett T.J. Butyrate delivered by butyrylated starch increases distal colonic epithelial apoptosis in carcinogen-treated rats. Carcinogenesis. 2011;33:197–202. doi: 10.1093/carcin/bgr254.
    1. Hamer H.M., Jonkers D.M., Bast A., Vanhoutvin S.A., Fischer M.A., Kodde A., Troost F.J., Venema K., Brummer R.J. Butyrate modulates oxidative stress in the colonic mucosa of healthy humans. Clin. Nutr. 2009;28:88–93. doi: 10.1016/j.clnu.2008.11.002.
    1. Kovarik J.J., Tillinger W., Hofer J., Hölzl M.A., Heinzl H., Saemann M.D., Zlabinger G.J. Impaired anti-inflammatory efficacy of n-butyrate in patients with IBD. Eur. J. Clin. Invest. 2011;41:291–298. doi: 10.1111/j.1365-2362.2010.02407.x.
    1. Liu H., Wang J., He T., Becker S., Zhang G., Li D., Ma X. Butyrate: A double-edged sword for health? Adv. Nutr. 2018;9:21–29. doi: 10.1093/advances/nmx009.
    1. Brown A.J., Goldsworthy S.M., Barnes A.A., Eilert M., Tcheang L., Daniels D., Muir A.I., Wigglesworth M.J., Kinghorn I., Fraser N.J., et al. The orphan g protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short-chain carboxylic acids. J. Biol. Chem. 2002;278:11312–11319. doi: 10.1074/jbc.M211609200.
    1. Blander J.M., Longman R.S., Iliev I.D., Sonnenberg G.F., Artis D. Regulation of inflammation by microbiota interactions with the host. Nature Immunol. 2017;18:851–860. doi: 10.1038/ni.3780.
    1. Jie Z., Xia H., Zhong S.L., Feng Q., Li S., Liang S., Zhong H., Liu Z., Gao Y., Zhao H., et al. The gut microbiome in atherosclerotic cardiovascular disease. Nature Com. 2017;8:845. doi: 10.1038/s41467-017-00900-1.
    1. Tilg H., Moschen A.R. Microbiota and diabetes: An evolving relationship. Gut. 2014;63:1513–1521. doi: 10.1136/gutjnl-2014-306928.
    1. Peterson L.W., Artis D. Intestinal epithelial cells: Regulators of barrier function and immune homeostasis. Nature Rev. Immunol. 2014;14:141–154. doi: 10.1038/nri3608.
    1. Blander J.M. Death in the intestinal epithelium—basic biology and implications for inflammatory bowel disease. FEBS J. 2016;283:2720–2730. doi: 10.1111/febs.13771.
    1. Scaldaferri F., Pizzoferrato M., Gerardi V., Lopetuso L., Gasbarrini A. The gut barrier: New acquisitions and therapeutic approaches. J. Clin. Gastroentol. 2012;46:S12–S17. doi: 10.1097/MCG.0b013e31826ae849.
    1. Sonnenburg J.L., Bäckhed F. Diet-microbiota interactions as moderators of human metabolism. Nature. 2016;535:56–64. doi: 10.1038/nature18846.
    1. Lagier J.C., Hugon P., Khelaifia S., Fournier P.E., La Scola B., Raoult D. The rebirth of culture in microbiology through the example of culturomics to study human gut microbiota. Clin. Micro. Rev. 2015;28:237–264. doi: 10.1128/CMR.00014-14.
    1. Rajilić-Stojanović M., de Vos W.M. The first 1000 cultured species of the human gastrointestinal microbiota. FEMS Micro. Rev. 2014;38:996–1047. doi: 10.1111/1574-6976.12075.
    1. Louis P., Flint H.J. Formation of propionate and butyrate by the human colonic microbiota. Environ. Micro. 2017;19:29–41. doi: 10.1111/1462-2920.13589.
    1. Lennon G., Balfe Á., Earley H., Devane L.A., Lavelle A., Winter D.C., Coffey J.C., O’Connell P.R. Influences of the colonic microbiome on the mucous gel layer in ulcerative colitis. Gut Microbes. 2014;5:277–476. doi: 10.4161/gmic.28793.
    1. Flint H.J., Scott K.P., Duncan S.H., Louis P., Forano E. Microbial degradation of complex carbohydrates in the gut. Gut Microbes. 2012;3:289–306. doi: 10.4161/gmic.19897.
    1. Cummings J.H., Englyst H.N. Fermentation in the human large intestine and the available substrates. Am. J. Clin. Nutr. 1987;45:1243–1255. doi: 10.1093/ajcn/45.5.1243.
    1. Louis P., Flint H.J. Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine. FEMS Micro. Lett. 2009;294:1–8. doi: 10.1111/j.1574-6968.2009.01514.x.
    1. Bach Knudsen K.E. Microbial degradation of whole-grain complex carbohydrates and impact on short-chain fatty acids and health. Adv. Nutr. 2015;6:206–213. doi: 10.3945/an.114.007450.
    1. Flint H.J., Bayer E.A., Rincon M.T., Lamed R., White B.A. Polysaccharide utilization by gut bacteria: Potential for new insights from genomic analysis. Nature Rev. Micro. 2008;6:121–131. doi: 10.1038/nrmicro1817.
    1. Walker A.W., Duncan S.H., Harmsen H.J., Holtrop G., Welling G.W., Flint H.J. The species composition of the human intestinal microbiota differs between particle-associated and liquid phase communities. Environ. Micro. 2008;10:3275–3283. doi: 10.1111/j.1462-2920.2008.01717.x.
    1. Flint H.J., Duncan S.H., Scott K.P., Louis P. Interactions and competition within the microbial community of the human colon: Links between diet and health. Environ. Microbiol. 2007;9:1101–1111. doi: 10.1111/j.1462-2920.2007.01281.x.
    1. Louis P., Scott K.P., Duncan S.H., Flint H.J. Understanding the effects of diet on bacterial metabolism in the large intestine. J. Appl. Microbiol. 2007;102:1197–1208. doi: 10.1111/j.1365-2672.2007.03322.x.
    1. Bach Knudsen K.E., Lærke H.N. Rye arabinoxylans: Molecular structure, physicochemical properties and physiological effects in the gastrointestinal tract. Cereal. Chem. 2010;87:353–362. doi: 10.1094/CCHEM-87-4-0353.
    1. Nielsen T.S., Lærke H.N., Theil P.K., Sørensen J.F., Saarinen M., Forssten S., Bach Knudsen K.E. Diets high in resistant starch and arabinoxylan modulate digestion processes and SCFA pool size in the large intestine and faecal microbial composition in pigs. Br. J. Nutr. 2014;112:1837–1849. doi: 10.1017/S000711451400302X.
    1. Hald S. Ph.D. Thesis. Aarhus University Hospital; Aarhus, Denmark: 2015. Effects of dietary fibres on gut microbiota, faecal short-chain fatty acids and intestinal inflammation in the metabolic syndrome.
    1. Schioldan A.G., Gregersen S., Hald S., Bjørnshave A., Bohl M., Hartmann B., Holst J.J., Stødkilde-Jørgensen H., Hermansen K. Effects of a diet rich in arabinoxylan and resistant starch compared with a diet rich in refined carbohydrates on postprandial metabolism and features of the metabolic syndrome. Euro. J. Nutr. 2018;57:795–807. doi: 10.1007/s00394-016-1369-8.
    1. Hald S., Schioldan A.G., Moore M.E., Dige A., Lærke H.N., Agnholt J., Knudsen K.E.B., Hermansen K., Marco M.L., Gregersen S., et al. Effects of arabinoxylan and resistant starch on intestinal microbiota and short-chain fatty acids in subjects with metabolic syndrome: A randomised crossover study. PLoS ONE. 2016;11:e0159223. doi: 10.1371/journal.pone.0159223.
    1. Duncan S.H., Louis P., Thomson J.M., Flint H.J. The role of pH in determining the species composition of the human colonic microbiota. Environ. Microbiol. 2009;11:2112–2122. doi: 10.1111/j.1462-2920.2009.01931.x.
    1. Gupta N., Martin P.M., Prasad P.D., Ganapathy V. SLC5A8 (SMCT1)-mediated transport of butyrate forms the basis for the tumor suppressive function of the transporter. Life. Sci. 2006;78:2419–2425. doi: 10.1016/j.lfs.2005.10.028.
    1. Cuff M.A., Lambert D.W., Shirazi-Beechey S.P. Substrate-induced regulation of the human colonic monocarboxylate transporter, MCT1. J. Physiol. 2002;539:361–371. doi: 10.1113/jphysiol.2001.014241.
    1. Haenen D., Souza da Silva C., Zhang J., Koopmans S.J., Bosch G., Vervoort J., Gerrits W.J., Kemp B., Smidt H., Muller M., et al. Resistant starch induces catabolic but suppresses immune and cell division pathways and changes the microbiome in the proximal colon of male pigs. J. Nutr. 2013;143:1889–1898. doi: 10.3945/jn.113.182154.
    1. Haenen D., Zhang J., Souza da Silva C., Bosch G., van der Meer I.M., van Arkel J., van den Borne J.J., Perez Gutierrez O., Smidt H., Kemp B., et al. A diet high in resistant starch modulates microbiota composition, SCFA concentrations, and gene expression in pig intestine. J. Nutr. 2013;143:274–283. doi: 10.3945/jn.112.169672.
    1. Nielsen T.S., Theil P.K., Purup S., Nørskov N.P., Bach Knudsen K.E. Effects of resistant starch and arabinoxylan on parameters related to large intestinal and metabolic health in pigs fed fat-rich diets. J. Agric. Food Chem. 2015;63:10418–10430. doi: 10.1021/acs.jafc.5b03372.
    1. Sleeth M.L., Thompson E.L., Ford H.E., Zac-Varghese S.E., Frost G. Free fatty acid receptor 2 and nutrient sensing: A proposed role for fibre, fermentable carbohydrates and short-chain fatty acids in appetite regulation. Nutr. Res. Rev. 2010;23:135–145. doi: 10.1017/S0954422410000089.
    1. Singh N., Gurav A., Sivaprakasam S., Brady E., Padia R., Shi H., Thangaraju M., Prasad P.D., Manicassamy S., Munn D.H., et al. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity. 2014;40:128–139. doi: 10.1016/j.immuni.2013.12.007.
    1. Thangaraju M., Cresci G.A., Liu K., Ananth S., Gnanaprakasam J.P., Browning D.D., Mellinger J.D., Smith S.B., Digby G.J., Lambert N.A., et al. Gpr109a is a G-protein–coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. Cancer Res. 2009;69:2826–2832. doi: 10.1158/0008-5472.CAN-08-4466.
    1. Chang P.V., Hao L., Offermanns S., Medzhitov R. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc. Nat. Acad Sci. 2014;111:2247–2252. doi: 10.1073/pnas.1322269111.
    1. Bindels L.B., Dewulf E.M., Delzenne N.M. GPR43/FFA2: Physiopathological relevance and therapeutic prospects. Trends Pharmacol. Sci. 2013;34:226–232. doi: 10.1016/j.tips.2013.02.002.
    1. Ingerslev A.K., Mutt S.J., Lærke H.N., Hedemann M.S., Theil P.K., Nielsen K.L., Jørgensen H., Herzig K.-H., Knudsen K.E.B. Postprandial PYY increase by resistant starch supplementation is independent of net portal appearance of short-chain fatty acids in pigs. PLoS ONE. 2017;12:e0185927. doi: 10.1371/journal.pone.0185927.
    1. Kaji I., Karaki S.-I., Tanaka R., Kuwahara A. Density distribution of free fatty acid receptor 2 (FFA2)-expressing and GLP-1-producing enteroendocrine l cells in human and rat lower intestine, and increased cell numbers after ingestion of fructo-oligosaccharide. J. Mol. Histol. 2011;42:27–38. doi: 10.1007/s10735-010-9304-4.
    1. Macia L., Tan J., Vieira A.T., Leach K., Stanley D., Luong S., Maruya M., Ian McKenzie C., Hijikata A., Wong C., et al. Metabolite-sensing receptors GPR43 and Gpr109a facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome. Nat. Commun. 2015;6:6734. doi: 10.1038/ncomms7734.
    1. Anderson J.M., Van Itallie C.M. Physiology and function of the tight junction. Cold Spring Harb. Perspect. Biol. 2009;1:a002584. doi: 10.1101/cshperspect.a002584.
    1. Cani P.D., Amar J., Iglesias M.A., Poggi M., Knauf C., Bastelica D., Neyrinck A.M., Fava F., Tuohy K.M., Chabo C., et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007;56:1761–1772. doi: 10.2337/db06-1491.
    1. Serino M., Luche E., Gres S., Baylac A., Bergé M., Cenac C., Waget A., Klopp P., Iacovoni J., Klopp C., et al. Metabolic adaptation to a high-fat diet is associated with a change in the gut microbiota. Gut. 2011;61:543–553. doi: 10.1136/gutjnl-2011-301012.
    1. Nymark M., Pietiläinen K.H., Kaartinen K., Pussinen P.J., Syrjänen J., Forsblom C., Pörsti I., Rissanen A., Kaprio J., Mustonen J., et al. Bacterial endotoxin activity in human serum is associated with dyslipidemia, insulin resistance, obesity, and chronic inflammation. Diabetes Care. 2011;34:1809–1815. doi: 10.2337/dc10-2197.
    1. Pussinen P.J., Havulinna A.S., Lehto M., Sundvall J., Salomaa V. Endotoxemia is associated with an increased risk of incident diabetes. Diabetes Care. 2011;34:392–397. doi: 10.2337/dc10-1676.
    1. Nielsen D.S.G., Jensen B.B., Theil P.K., Nielsen T.S., Bach Knudsen K.E., Purup S. Effect of butyrate and fermentation products on epithelial integrity in a mucus-secreting human colon cell line. J. Funct. Foods. 2018;40:9–17. doi: 10.1016/j.jff.2017.10.023.
    1. Peng L., He Z., Chen W., Holzman I.R., Lin J. Effects of butyrate on intestinal barrier function in a Caco-2 cell monolayer model of intestinal barrier. Pediatric. Res. 2007;61:37–41. doi: 10.1203/01.pdr.0000250014.92242.f3.
    1. Peng L., Li Z.-R., Green R.S., Holzman I.R., Lin J. Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. J. Nutr. 2009;139:1619–1625. doi: 10.3945/jn.109.104638.
    1. Burger-van Paassen N., Vincent A., Puiman P.J., Van Der Sluis M., Bouma J., Boehm G., Van Goudoever J.B., Van Seuningen I., Renes I.B. The regulation of intestinal mucin MUC2 expression by short-chain fatty acids: Implications for epithelial protection. Biochem. J. 2009;420:211–219. doi: 10.1042/BJ20082222.
    1. Hedemann M.S., Theil P.K., Knudsen K.B. The thickness of the intestinal mucous layer in the colon of rats fed various sources of non-digestible carbohydrates is positively correlated with the pool of SCFA but negatively correlated with the proportion of butyric acid in digesta. Br. J. Nutr. 2009;102:117–125. doi: 10.1017/S0007114508143549.
    1. Barcelo A., Claustre J., Moro F., Chayvialle J., Cuber J., Plaisancié P. Mucin secretion is modulated by luminal factors in the isolated vascularly perfused rat colon. Gut. 2000;46:218–224. doi: 10.1136/gut.46.2.218.
    1. Shimotoyodome A., Meguro S., Hase T., Tokimitsu I., Sakata T. Short chain fatty acids but not lactate or succinate stimulate mucus release in the rat colon. Comp. Biochem. Physiol. A Mol. Integr. Physiol. 2000;125:525–531. doi: 10.1016/S1095-6433(00)00183-5.
    1. Chen H., Mao X., He J., Yu B., Huang Z., Yu J., Zheng P., Chen D. Dietary fibre affects intestinal mucosal barrier function and regulates intestinal bacteria in weaning piglets. Br. J. Nutr. 2013;110:1837–1848. doi: 10.1017/S0007114513001293.
    1. Morita T., Tanabe H., Sugiyama K., Kasaoka S., Kiriyama S. Dietary resistant starch alters the characteristics of colonic mucosa and exerts a protective effect on trinitrobenzene sulfonic acid-induced colitis in rats. Biosci. Biotech. Biochem. 2004;68:2155–2164. doi: 10.1271/bbb.68.2155.
    1. Rodríguez-Cabezas M.E., Camuesco D., Arribas B., Garrido-Mesa N., Comalada M., Bailón E., Cueto-Sola M., Utrilla P., Guerra-Hernández E., Pérez-Roca C., et al. The combination of fructooligosaccharides and resistant starch shows prebiotic additive effects in rats. Clin. Nutr. 2010;29:832–839. doi: 10.1016/j.clnu.2010.05.005.
    1. Calder P.C., Albers R., Antoine J.-M., Blum S., Bourdet-Sicard R., Ferns G., Folkerts G., Friedmann P., Frost G., Guarner F., et al. Inflammatory disease processes and interactions with nutrition. Br. J. Nutr. 2009;101:1–45. doi: 10.1017/S0007114509377867.
    1. Jobin C., Sartor R.B. The IκB/NF-κB system: A key determinant of mucosal inflammation and protection. Am. J. Physiol. Cell Physiol. 2000;278:C451–C462. doi: 10.1152/ajpcell.2000.278.3.C451.
    1. Bours V., Bonizzi G., Bentires-Alj M., Bureau F., Piette J., Lekeux P., Merville M.-P. NF-κB activation in response to toxical and therapeutical agents: Role in inflammation and cancer treatment. Toxicol. 2000;153:27–38. doi: 10.1016/S0300-483X(00)00302-4.
    1. Elce A., Amato F., Zarrilli F., Calignano A., Troncone R., Castaldo G., Canani R.B. Butyrate modulating effects on pro-inflammatory pathways in human intestinal epithelial cells. Benef. Microbes. 2017;8:841–847. doi: 10.3920/BM2016.0197.
    1. Calder P.C., Ahluwalia N., Albers R., Bosco N., Bourdet-Sicard R., Haller D., Holgate S.T., Jönsson L.S., Latulippe M.E., Marcos A., et al. A consideration of biomarkers to be used for evaluation of inflammation in human nutritional studies. Br. J. Nutr. 2013;109:S1–S34. doi: 10.1017/S0007114512005119.
    1. Van der Beek C.M., Dejong C.H.C., Troost F.J., Masclee A.A.M., Lenaerts K. Role of short-chain fatty acids in colonic inflammation, carcinogenesis, and mucosal protection and healing. Nutr. Rev. 2017;75:286–305. doi: 10.1093/nutrit/nuw067.
    1. Meijer K., de Vos P., Priebe M.G. Butyrate and other short-chain fatty acids as modulators of immunity: What relevance for health? Curr. Opin. Clin. Nutr. Met. Care. 2010;13:715–721. doi: 10.1097/MCO.0b013e32833eebe5.
    1. Vinolo M.A., Rodrigues H.G., Hatanaka E., Sato F.T., Sampaio S.C., Curi R. Suppressive effect of short-chain fatty acids on production of proinflammatory mediators by neutrophils. J. Nutr. Biochem. 2011;22:849–855. doi: 10.1016/j.jnutbio.2010.07.009.
    1. Andoh A., Bamba T., Sasaki M. Physiological and anti-inflammatory roles of dietary fiber and butyrate in intestinal functions. J. Par. Enteral. Nutr. 1999;23:S70–S73. doi: 10.1177/014860719902300518.
    1. Segain J., De La Blétiere D.R., Bourreille A., Leray V., Gervois N., Rosales C., Ferrier L., Bonnet C., Blottiere H., Galmiche J. Butyrate inhibits inflammatory responses through NFκB inhibition: Implications for Crohn’s disease. Gut. 2000;47:397–403. doi: 10.1136/gut.47.3.397.
    1. Song M., Xia B., Li J. Effects of topical treatment of sodium butyrate and 5-aminosalicylic acid on expression of trefoil factor 3, interleukin 1β, and nuclear factor κb in trinitrobenzene sulphonic acid induced colitis in rats. Postgrad. Med. J. 2006;82:130–135. doi: 10.1136/pgmj.2005.037945.
    1. Vulevic J., Juric A., Tzortzis G., Gibson G.R. A mixture of trans-galactooligosaccharides reduces markers of metabolic syndrome and modulates the fecal microbiota and immune function of overweight adults. J. Nutr. 2013;143:324–331. doi: 10.3945/jn.112.166132.
    1. Rodríguez-Cabezas M.E., Galvez J., Lorente M.D., Concha A., Camuesco D., Azzouz S., Osuna A., Redondo L., Zarzuelo A. Dietary fiber down-regulates colonic tumor necrosis factor α and nitric oxide production in trinitrobenzenesulfonic acid-induced colitic rats. J. Nutr. 2002;132:3263–3271. doi: 10.1093/jn/132.11.3263.
    1. Hijová E., Szabadosova V., Štofilová J., Hrčková G. Chemopreventive and metabolic effects of inulin on colon cancer development. J. Vet. Sci. 2013;14:387–393. doi: 10.4142/jvs.2013.14.4.387.
    1. Alex S., Lange K., Amolo T., Grinstead J.S., Haakonsson A.K., Szalowska E., Koppen A., Mudde K., Haenen D., Al-Lahham Sa’ad., et al. Short chain fatty acids stimulate angiopoietin-like 4 synthesis in human colon adenocarcinoma cells by activating pparγ. Mol. Cell. Biol. 2013;33:1303–1316. doi: 10.1128/MCB.00858-12.
    1. Kinoshita M., Suzuki Y., Saito Y. Butyrate reduces colonic paracellular permeability by enhancing ppargamma activation. Biochem. Biophys. Res. Commun. 2002;293:827–831. doi: 10.1016/S0006-291X(02)00294-2.
    1. Hontecillas R., Bassaganya-Riera J. Peroxisome proliferator-activated receptor γ is required for regulatory CD4+ T cell-mediated protection against colitis. J. Immunol. 2007;178:2940–2949. doi: 10.4049/jimmunol.178.5.2940.
    1. Bassaganya-Riera J., Hontecillas R. CLA and n-3 PUFA differentially modulate clinical activity and colonic PPAR-responsive gene expression in a pig model of experimental IBD. Clin. Nutr. 2006;25:454–465. doi: 10.1016/j.clnu.2005.12.008.
    1. Lewis J.D., Lichtenstein G.R., Deren J.J., Sands B.E., Hanauer S.B., Katz J.A., Lashner B., Present D.H., Chuai S., Ellenberg J.H., et al. Rosiglitazone for active ulcerative colitis: A randomized placebo-controlled trial. Gastroenterol. 2008;134:688–695. doi: 10.1053/j.gastro.2007.12.012.
    1. Da Silva C.S., Haenen D., Koopmans S.J., Hooiveld G.J., Bosch G., Bolhuis J.E., Kemp B., Müller M., Gerrits W.J. Effects of resistant starch on behaviour, satiety-related hormones and metabolites in growing pigs. Animal. 2014;8:1402–1411. doi: 10.1017/S1751731114001116.
    1. Bassaganya-Riera J., DiGuardo M., Viladomiu M., de Horna A., Sanchez S., Einerhand A.W., Sanders L., Hontecillas R. Soluble fibers and resistant starch ameliorate disease activity in interleukin-10-deficient mice with inflammatory bowel disease. J. Nutr. 2011;141:1318–1325. doi: 10.3945/jn.111.139022.
    1. Tan S., Seow T.K., Liang R.C.M., Koh S., Lee C.P., Chung M.C., Hooi S.C. Proteome analysis of butyrate-treated human colon cancer cells (HT-29) Inter. J. Cancer. 2002;98:523–531. doi: 10.1002/ijc.10236.
    1. Fernandez-Real J.M., Pickup J.C. Innate immunity, insulin resistance and type 2 diabetes. Trends Endocrin. Met. 2008;19:10–16. doi: 10.1016/j.tem.2007.10.004.
    1. Kolb H., Mandrup-Poulsen T. The global diabetes epidemic as a consequence of lifestyle-induced low-grade inflammation. Diabetologia. 2010;53:10–20. doi: 10.1007/s00125-009-1573-7.
    1. Ajani U.A., Ford E.S., Mokdad A.H. Dietary fiber and c-reactive protein: Findings from national health and nutrition examination survey data. J. Nutr. 2004;134:1181–1185. doi: 10.1093/jn/134.5.1181.
    1. Ma Y., Griffith J.A., Chasan-Taber L., Olendzki B.C., Jackson E., Stanek E.J., III, Li W., Pagoto S.L., Hafner A.R., Ockene I.S. Association between dietary fiber and serum C-reactive protein. Am. J. Clin. Nutr. 2006;83:760–766. doi: 10.1093/ajcn/83.4.760.
    1. Qi L., Van Dam R.M., Liu S., Franz M., Mantzoros C., Hu F.B. Whole-grain, bran, and cereal fiber intakes and markers of systemic inflammation in diabetic women. Diabetes Care. 2006;29:207–211. doi: 10.2337/diacare.29.02.06.dc05-1903.
    1. Wannamethee S.G., Whincup P.H., Thomas M., Sattar N. Associations between dietary fiber and inflammation, hepatic function and risk of type 2 diabetes in older men: Potential mechanisms for benefits of fiber on diabetes risk. Diabetes Care. 2009;32:1823–1825. doi: 10.2337/dc09-0477.
    1. Vulevic J., Drakoularakou A., Yaqoob P., Tzortzis G., Gibson G.R. Modulation of the fecal microflora profile and immune function by a novel trans-galactooligosaccharide mixture (B-GOS) in healthy elderly volunteers. Am. J. Clinl. Nutr. 2008;88:1438–1446.
    1. Guigoz Y., Rochat F., Perruisseau-Carrier G., Rochat I., Schiffrin E. Effects of oligosaccharide on the faecal flora and non-specific immune system in elderly people. Nutr. Res. 2002;22:13–25. doi: 10.1016/S0271-5317(01)00354-2.
    1. Peterson C.M., Beyl R.A., Marlatt K.L., Martin C.K., Aryana K.J., Marco M.L., Martin R.J., Keenan M.J., Ravussin E. Effect of 12 wk of resistant starch supplementation on cardiometabolic risk factors in adults with prediabetes: A randomized controlled trial. Am. J. Clin. Nutr. 2018;108:492–501. doi: 10.1093/ajcn/nqy121.
    1. Uusitupa M., Hermansen K., Savolainen M., Schwab U., Kolehmainen M., Brader L., Mortensen L., Cloetens L., Johansson-Persson A., Önning G., et al. Effects of an isocaloric healthy nordic diet on insulin sensitivity, lipid profile and inflammation markers in metabolic syndrome–a randomized study (SYSDIET) J. Inter. Med. 2013;274:52–66. doi: 10.1111/joim.12044.
    1. Kolehmainen M., Ulven S.M., Paananen J., de Mello V., Schwab U., Carlberg C., Myhrstad M., Pihlajamaki J., Dungner E., Sjolin E., et al. Healthy nordic diet downregulates the expression of genes involved in inflammation in subcutaneous adipose tissue in individuals with features of the metabolic syndrome. Am. J. Clin. Nutr. 2015;101:228–239. doi: 10.3945/ajcn.114.092783.
    1. Johansson-Persson A., Ulmius M., Cloetens L., Karhu T., Herzig K.-H., Önning G. A high intake of dietary fiber influences c-reactive protein and fibrinogen, but not glucose and lipid metabolism, in mildly hypercholesterolemic subjects. Euro. J. Nutr. 2014;53:39–48. doi: 10.1007/s00394-013-0496-8.
    1. Brownlee I.A., Moore C., Chatfield M., Richardson D.P., Ashby P., Kuznesof S.A., Jebb S.A., Seal C.J. Markers of cardiovascular risk are not changed by increased whole-grain intake: The wholeheart study, a randomised, controlled dietary intervention. Br. J. Nutr. 2010;104:125–134. doi: 10.1017/S0007114510000644.
    1. Giacco R., Lappi J., Costabile G., Kolehmainen M., Schwab U., Landberg R., Uusitupa M., Poutanen K., Pacini G., Rivellese A.A., et al. Effects of rye and whole wheat versus refined cereal foods on metabolic risk factors: A randomised controlled two-centre intervention study. Clin. Nutr. 2013;32:941–949. doi: 10.1016/j.clnu.2013.01.016.
    1. Robertson M.D., Wright J.W., Loizon E., Debard C., Vidal H., Shojaee-Moradie F., Russell-Jones D., Umpleby A.M. Insulin-sensitizing effects on muscle and adipose tissue after dietary fiber intake in men and women with metabolic syndrome. J. Clin. Endocrinol. Metab. 2012;97:3326–3332. doi: 10.1210/jc.2012-1513.
    1. Johnston K., Thomas E.L., Bell J.D., Frost G., Robertson M.D. Resistant starch improves insulin sensitivity in metabolic syndrome. Diabet. Med. 2010;27:391–397. doi: 10.1111/j.1464-5491.2010.02923.x.
    1. Johansson E.V., Nilsson A.C., Östman E.M., Björck I.M. Effects of indigestible carbohydrates in barley on glucose metabolism, appetite and voluntary food intake over 16 h in healthy adults. Nutr. J. 2013;12:46. doi: 10.1186/1475-2891-12-46.
    1. Nilsson A.C., Ostman E.M., Holst J.J., Bjorck I.M. Including indigestible carbohydrates in the evening meal of healthy subjects improves glucose tolerance, lowers inflammatory markers, and increases satiety after a subsequent standardized breakfast. J. Nutr. 2008;138:732–739. doi: 10.1093/jn/138.4.732.
    1. Priebe M.G., Wang H., Weening D., Schepers M., Preston T., Vonk R.J. Factors related to colonic fermentation of nondigestible carbohydrates of a previous evening meal increase tissue glucose uptake and moderate glucose-associated inflammation. Am. J. Clin. Nutr. 2010;91:90–97. doi: 10.3945/ajcn.2009.28521.
    1. Sandberg J.C., Bjorck I.M.E., Nilsson A.C. Effects of whole grain rye, with and without resistant starch type 2 supplementation, on glucose tolerance, gut hormones, inflammation and appetite regulation in an 11–14.5 hour perspective; a randomized controlled study in healthy subjects. Nutr. J. 2017;16:25. doi: 10.1186/s12937-017-0246-5.

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