Ketogenic Diet and Microbiota: Friends or Enemies?

Antonio Paoli, Laura Mancin, Antonino Bianco, Ewan Thomas, João Felipe Mota, Fabio Piccini, Antonio Paoli, Laura Mancin, Antonino Bianco, Ewan Thomas, João Felipe Mota, Fabio Piccini

Abstract

Over the last years, a growing body of evidence suggests that gut microbial communities play a fundamental role in many aspects of human health and diseases. The gut microbiota is a very dynamic entity influenced by environment and nutritional behaviors. Considering the influence of such a microbial community on human health and its multiple mechanisms of action as the production of bioactive compounds, pathogens protection, energy homeostasis, nutrients metabolism and regulation of immunity, establishing the influences of different nutritional approach is of pivotal importance. The very low carbohydrate ketogenic diet is a very popular dietary approach used for different aims: from weight loss to neurological diseases. The aim of this review is to dissect the complex interactions between ketogenic diet and gut microbiota and how this large network may influence human health.

Keywords: gut microbiome; gut microbiota; intestinal microbiome; ketogenic diet; ketogenic diet and fat.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The influence of a very low carbohydrate ketogenic diet and ketone bodies in gut health. BHB: β-hydroxybutyrate, AcAc: Acetoacetate.
Figure 2
Figure 2
Effects of ketogenic diet on different tissues and the microbiome. KD has a contradictory role on hunger but the net effect is anorexigenic. KD Exerts orexigenic effects: The increase of brain GABA (γ-aminobutyric acid) through BHB (β-hydroxybutyric acid); the increase of AMP (adenosine monophosphate -activated protein) phosphorylation via BHB; the increase of circulating level of adiponectin; the decreases of ROS (reactive oxygen species). KD Exerts anorexigenic effect: the increase of circulating post meal FFA (free fatty acids); a maintained meal’s response of CCK (cholecystokinin); a decrease of circulating ghrelin; a decrease of AMP phosphorylation; a decrease of AgRP (agouti-related protein) expression. KD has positive effects on Alzheimer’s disease through: an increase levels of CBF (cerebral blood flow) in VMH (ventromedial hypothalamus); a decrease expression of mTOR (mammalian target of rapamycin) by the increase of the level of eNOS (endothelial nitric oxide synthase) protein expression; an increased expression of P-gp (P-glycoprotein), which transport Aβ (amyloid-β) plaques; an improvement of BBB’s (blood–brain-barrier) integrity. KD has beneficial effects on epileptic seizure by the modulation of hippocampal GABA/glutamate ratio. It exerts anti-seizure effects through: An increase level of GABA, an increase content of GABA: glutamate ratio. KD plays a main role on fat loss. It exerts positive effects on adipose tissue through: a decrease of liposynthesis, an increase of lipid oxidation and an increase in adiponectin. KD has a contradictory role on microbiome. KD generally exerts its effect through: a decrease in α diversity (the diversity in a single ecosystem/sample) and a decrease in richness (number of different species in a habitat/sample). KD influences the gut health through metabolites produced by different microbes: an increase/decrease in SCFA (short chain fatty acids), an increase in H2S (hydrogen sulfide) and a decrease in lactate. KD to microbiome to the brain: KD may influence the CNS (central nervous system) not only directly but also indirectly. The KD effects on the brain are supposed to be mediated by microbiota through an increase of SCFAs and a decrease of γ-glutamyl amino acid. A. muciniphila and Lactobacillus are known as SCFAs producers. SCFAs are transported by monocarboxylase transporters expressed at BBB. Desulfovibrio has the ability to produce hydrogen sulfide and, as a consequence, impair intestinal mucosal barrier. A reduction in Desulfovibrio and an enhancement in A. muciniphila and Lactobacillus may facilitate BBB and neurovascular amelioration. KD to microbiome to the adipose tissue: KD may indirectly influence the adipose tissue by the microbiota through a decrease in glycemia via adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, an increase in insulin sensitivity and an increase in SCFAs. The great amount of A. muciniphila and Lactobacillus spp. led to the reduction of body weight and glycemia. It has been demonstrated that patient with type 2 diabetes, treated with metformin, revealed higher level of A. muciniphila, may be to the ability of metformin on decreasing body weight by the activation of AMPK pathways (amp-activated protein kinase). A. muciniphila is related with the enhancement of insulin sensitivity and Lactobacillus may be playing the same effects through SFCAs production: Several studies showed that Lactobacillus is strictly connected with body weight loss.

References

    1. Thursby E., Juge N. Introduction to the human gut microbiota. Biochem. J. 2017;474:1823–1836. doi: 10.1042/BCJ20160510.
    1. Gill S.R., Pop M., Deboy R.T., Eckburg P.B., Turnbaugh P.J., Samuel B.S., Gordon J.I., Relman D.A., Fraser-Liggett C.M., Nelson K.E. Metagenomic analysis of the human distal gut microbiome. Science. 2006;312:1355–1359. doi: 10.1126/science.1124234.
    1. Backhed F., Ley R.E., Sonnenburg J.L., Peterson D.A., Gordon J.I. Host-bacterial mutualism in the human intestine. Science. 2005;307:1915–1920. doi: 10.1126/science.1104816.
    1. Weinstock G.M. Genomic approaches to studying the human microbiota. Nature. 2012;489:250–256. doi: 10.1038/nature11553.
    1. Koedooder R., Mackens S., Budding A., Fares D., Blockeel C., Laven J., Schoenmakers S. Identification and evaluation of the microbiome in the female and male reproductive tracts. Hum. Reprod. Update. 2019;25:298–325. doi: 10.1093/humupd/dmy048.
    1. Oulas A., Pavloudi C., Polymenakou P., Pavlopoulos G.A., Papanikolaou N., Kotoulas G., Arvanitidis C., Iliopoulos I. Metagenomics: Tools and insights for analyzing next-generation sequencing data derived from biodiversity studies. Bioinform. Biol. Insights. 2015;9:75–88. doi: 10.4137/BBI.S12462.
    1. Group N.H.W., Peterson J., Garges S., Giovanni M., McInnes P., Wang L., Schloss J.A., Bonazzi V., McEwen J.E., Wetterstrand K.A., et al. The nih human microbiome project. Genome Res. 2009;19:2317–2323. doi: 10.1101/gr.096651.109.
    1. Taneja V. Arthritis susceptibility and the gut microbiome. Febs Lett. 2014;588:4244–4249. doi: 10.1016/j.febslet.2014.05.034.
    1. Morrison D.J., Preston T. Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes. 2016;7:189–200. doi: 10.1080/19490976.2015.1134082.
    1. Annalisa N., Alessio T., Claudette T.D., Erald V., Antonino d.L., Nicola D.D. Gut microbioma population: An indicator really sensible to any change in age, diet, metabolic syndrome, and life-style. Mediat. Inflamm. 2014;2014:901308. doi: 10.1155/2014/901308.
    1. Rodriguez J.M., Murphy K., Stanton C., Ross R.P., Kober O.I., Juge N., Avershina E., Rudi K., Narbad A., Jenmalm M.C., et al. The composition of the gut microbiota throughout life, with an emphasis on early life. Microb. Ecol. Health Dis. 2015;26:26050. doi: 10.3402/mehd.v26.26050.
    1. Gibiino G., Lopetuso L.R., Scaldaferri F., Rizzatti G., Binda C., Gasbarrini A. Exploring bacteroidetes: Metabolic key points and immunological tricks of our gut commensals. Dig. Liver Dis. 2018;50:635–639. doi: 10.1016/j.dld.2018.03.016.
    1. Fouhy F., Watkins C., Hill C.J., O’Shea C.A., Nagle B., Dempsey E.M., O’Toole P.W., Ross R.P., Ryan C.A., Stanton C. Perinatal factors affect the gut microbiota up to four years after birth. Nat. Commun. 2019;10:1517. doi: 10.1038/s41467-019-09252-4.
    1. Koliada A., Syzenko G., Moseiko V., Budovska L., Puchkov K., Perederiy V., Gavalko Y., Dorofeyev A., Romanenko M., Tkach S., et al. Association between body mass index and firmicutes/bacteroidetes ratio in an adult ukrainian population. BMC Microbiol. 2017;17:120. doi: 10.1186/s12866-017-1027-1.
    1. Nagpal R., Mainali R., Ahmadi S., Wang S., Singh R., Kavanagh K., Kitzman D.W., Kushugulova A., Marotta F., Yadav H. Gut microbiome and aging: Physiological and mechanistic insights. Nutr Healthy Aging. 2018;4:267–285. doi: 10.3233/NHA-170030.
    1. El Kaoutari A., Armougom F., Gordon J.I., Raoult D., Henrissat B. The abundance and variety of carbohydrate-active enzymes in the human gut microbiota. Nat. Rev. Microbiol. 2013;11:497–504. doi: 10.1038/nrmicro3050.
    1. Sonnenburg E.D., Sonnenburg J.L. Starving our microbial self: The deleterious consequences of a diet deficient in microbiota-accessible carbohydrates. Cell Metab. 2014;20:779–786. doi: 10.1016/j.cmet.2014.07.003.
    1. LeBlanc J.G., Milani C., de Giori G.S., Sesma F., van Sinderen D., Ventura M. Bacteria as vitamin suppliers to their host: A gut microbiota perspective. Curr. Opin. Biotechnol. 2013;24:160–168. doi: 10.1016/j.copbio.2012.08.005.
    1. Vrieze A., Holleman F., Zoetendal E.G., de Vos W.M., Hoekstra J.B., Nieuwdorp M. The environment within: How gut microbiota may influence metabolism and body composition. Diabetologia. 2010;53:606–613. doi: 10.1007/s00125-010-1662-7.
    1. Topping D.L., Clifton P.M. Short-chain fatty acids and human colonic function: Roles of resistant starch and nonstarch polysaccharides. Physiol. Rev. 2001;81:1031–1064. doi: 10.1152/physrev.2001.81.3.1031.
    1. Louis P., Flint H.J. Formation of propionate and butyrate by the human colonic microbiota. Env. Microbiol. 2017;19:29–41. doi: 10.1111/1462-2920.13589.
    1. Lundin A., Bok C.M., Aronsson L., Bjorkholm B., Gustafsson J.A., Pott S., Arulampalam V., Hibberd M., Rafter J., Pettersson S. Gut flora, toll-like receptors and nuclear receptors: A tripartite communication that tunes innate immunity in large intestine. Cell. Microbiol. 2008;10:1093–1103. doi: 10.1111/j.1462-5822.2007.01108.x.
    1. Nemeroff C.B. The role of gaba in the pathophysiology and treatment of anxiety disorders. Psychopharmacol. Bull. 2003;37:133–146.
    1. Cryan J.F., Kaupmann K. Don’t worry ‘b’ happy!: A role for gaba(b) receptors in anxiety and depression. Trends Pharm. Sci. 2005;26:36–43. doi: 10.1016/j.tips.2004.11.004.
    1. Barrett E., Ross R.P., O’Toole P.W., Fitzgerald G.F., Stanton C. γ-aminobutyric acid production by culturable bacteria from the human intestine. J. Appl. Microbiol. 2012;113:411–417. doi: 10.1111/j.1365-2672.2012.05344.x.
    1. Bravo J.A., Forsythe P., Chew M.V., Escaravage E., Savignac H.M., Dinan T.G., Bienenstock J., Cryan J.F. Ingestion of lactobacillus strain regulates emotional behavior and central gaba receptor expression in a mouse via the vagus nerve. Proc. Natl. Acad. Sci. USA. 2011;108:16050–16055. doi: 10.1073/pnas.1102999108.
    1. Kim D.Y., Camilleri M. Serotonin: A mediator of the brain-gut connection. Am. J. Gastroenterol. 2000;95:2698–2709.
    1. Yano J.M., Yu K., Donaldson G.P., Shastri G.G., Ann P., Ma L., Nagler C.R., Ismagilov R.F., Mazmanian S.K., Hsiao E.Y. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015;161:264–276. doi: 10.1016/j.cell.2015.02.047.
    1. Agus A., Planchais J., Sokol H. Gut microbiota regulation of tryptophan metabolism in health and disease. Cell Host Microbe. 2018;23:716–724. doi: 10.1016/j.chom.2018.05.003.
    1. Namkung J., Kim H., Park S. Peripheral serotonin: A new player in systemic energy homeostasis. Mol. Cells. 2015;38:1023–1028.
    1. Gentile C.L., Weir T.L. The gut microbiota at the intersection of diet and human health. Science. 2018;362:776–780. doi: 10.1126/science.aau5812.
    1. David L.A., Maurice C.F., Carmody R.N., Gootenberg D.B., Button J.E., Wolfe B.E., Ling A.V., Devlin A.S., Varma Y., Fischbach M.A., et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505:559–563. doi: 10.1038/nature12820.
    1. Klimenko N.S., Tyakht A.V., Popenko A.S., Vasiliev A.S., Altukhov I.A., Ischenko D.S., Shashkova T.I., Efimova D.A., Nikogosov D.A., Osipenko D.A., et al. Microbiome responses to an uncontrolled short-term diet intervention in the frame of the citizen science project. Nutrients. 2018;10:567. doi: 10.3390/nu10050576.
    1. De Filippo C., Cavalieri D., Di Paola M., Ramazzotti M., Poullet J.B., Massart S., Collini S., Pieraccini G., Lionetti P. Impact of diet in shaping gut microbiota revealed by a comparative study in children from europe and rural africa. Proc. Natl. Acad. Sci. USA. 2010;107:14691–14696. doi: 10.1073/pnas.1005963107.
    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. 2018;57:1–24. doi: 10.1007/s00394-017-1445-8.
    1. Zinocker M.K., Lindseth I.A. The western diet-microbiome-host interaction and its role in metabolic disease. Nutrients. 2018;10:365. doi: 10.3390/nu10030365.
    1. Duan Y., Zeng L., Zheng C., Song B., Li F., Kong X., Xu K. Inflammatory links between high fat diets and diseases. Front. Immunol. 2018;9:2649. doi: 10.3389/fimmu.2018.02649.
    1. Mills S., Stanton C., Lane J.A., Smith G.J., Ross R.P. Precision nutrition and the microbiome, part I: Current state of the science. Nutrients. 2019;11:923. doi: 10.3390/nu11040923.
    1. Candido F.G., Valente F.X., Grzeskowiak L.M., Moreira A.P.B., Rocha D., Alfenas R.C.G. Impact of dietary fat on gut microbiota and low-grade systemic inflammation: Mechanisms and clinical implications on obesity. Int. J. Food Sci. Nutr. 2018;69:125–143. doi: 10.1080/09637486.2017.1343286.
    1. Reddel S., Putignani L., Del Chierico F. The impact of low-fodmaps, gluten-free, and ketogenic diets on gut microbiota modulation in pathological conditions. Nutrients. 2019;11:373. doi: 10.3390/nu11020373.
    1. De Wit N., Derrien M., Bosch-Vermeulen H., Oosterink E., Keshtkar S., Duval C., de Vogel-van den Bosch J., Kleerebezem M., Muller M., van der Meer R. Saturated fat stimulates obesity and hepatic steatosis and affects gut microbiota composition by an enhanced overflow of dietary fat to the distal intestine. Am. J. Physiol. Gastrointest. Liver Physiol. 2012;303:G589–G599. doi: 10.1152/ajpgi.00488.2011.
    1. Varju P., Farkas N., Hegyi P., Garami A., Szabo I., Illes A., Solymar M., Vincze A., Balasko M., Par G., et al. Low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet improves symptoms in adults suffering from irritable bowel syndrome (IBS) compared to standard IBS diet: A meta-analysis of clinical studies. PLoS ONE. 2017;12:e0182942. doi: 10.1371/journal.pone.0182942.
    1. Wong W.M. Restriction of fodmap in the management of bloating in irritable bowel syndrome. Singap. Med. J. 2016;57:476–484. doi: 10.11622/smedj.2016152.
    1. Bascunan K.A., Vespa M.C., Araya M. Celiac disease: Understanding the gluten-free diet. Eur. J. Nutr. 2017;56:449–459. doi: 10.1007/s00394-016-1238-5.
    1. Paoli A., Rubini A., Volek J.S., Grimaldi K.A. Beyond weight loss: A review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. Eur. J. Clin. Nutr. 2013;67:789–796. doi: 10.1038/ejcn.2013.116.
    1. Stafstrom C.E., Rho J.M. The ketogenic diet as a treatment paradigm for diverse neurological disorders. Front. Pharm. 2012;3:59. doi: 10.3389/fphar.2012.00059.
    1. Murtaza N., Burke L.M., Vlahovich N., Charlesson B., O’Neill H., Ross M.L., Campbell K.L., Krause L., Morrison M. The effects of dietary pattern during intensified training on stool microbiota of elite race walkers. Nutrients. 2019;11:261. doi: 10.3390/nu11020261.
    1. Cooder H.R. Epilepsy in children: With particular reference to the ketogenic diet. Cal. West. Med. 1933;39:169–173.
    1. Perez-Guisado J. Ketogenic diets: Additional benefits to the weight loss and unfounded secondary effects. Arch. Lat. Nutr. 2008;58:323–329.
    1. Tagliabue A., Ferraris C., Uggeri F., Trentani C., Bertoli S., de Giorgis V., Veggiotti P., Elli M. Short-term impact of a classical ketogenic diet on gut microbiota in GLUT1 deficiency syndrome: A 3-month prospective observational study. Clin. Nutr Espen. 2017;17:33–37. doi: 10.1016/j.clnesp.2016.11.003.
    1. Ma D., Wang A.C., Parikh I., Green S.J., Hoffman J.D., Chlipala G., Murphy M.P., Sokola B.S., Bauer B., Hartz A.M.S., et al. Ketogenic diet enhances neurovascular function with altered gut microbiome in young healthy mice. Sci. Rep. 2018;8:6670. doi: 10.1038/s41598-018-25190-5.
    1. Swidsinski A., Dorffel Y., Loening-Baucke V., Gille C., Goktas O., Reisshauer A., Neuhaus J., Weylandt K.H., Guschin A., Bock M. Reduced mass and diversity of the colonic microbiome in patients with multiple sclerosis and their improvement with ketogenic diet. Front. Microbiol. 2017;8:1141. doi: 10.3389/fmicb.2017.01141.
    1. Olson C.A., Vuong H.E., Yano J.M., Liang Q.Y., Nusbaum D.J., Hsiao E.Y. The gut microbiota mediates the anti-seizure effects of the ketogenic diet. Cell. 2018;174:497. doi: 10.1016/j.cell.2018.06.051.
    1. Veech R.L. The therapeutic implications of ketone bodies: The effects of ketone bodies in pathological conditions: Ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism. Prostaglandins Leukot. Essent. Fat. Acids. 2004;70:309–319. doi: 10.1016/j.plefa.2003.09.007.
    1. Kwan P., Brodie M.J. Early identification of refractory epilepsy. N. Engl. J. Med. 2000;342:314–319. doi: 10.1056/NEJM200002033420503.
    1. Klepper J. GLUT1 deficiency syndrome in clinical practice. Epilepsy Res. 2012;100:272–277. doi: 10.1016/j.eplepsyres.2011.02.007.
    1. Choi I.Y., Piccio L., Childress P., Bollman B., Ghosh A., Brandhorst S., Suarez J., Michalsen A., Cross A.H., Morgan T.E., et al. A diet mimicking fasting promotes regeneration and reduces autoimmunity and multiple sclerosis symptoms. Cell Rep. 2016;15:2136–2146. doi: 10.1016/j.celrep.2016.05.009.
    1. Liu Y.M., Wang H.S. Medium-chain triglyceride ketogenic diet, an effective treatment for drug-resistant epilepsy and a comparison with other ketogenic diets. Biomed. J. 2013;36:9–15. doi: 10.4103/2319-4170.107154.
    1. Miranda M.J., Turner Z., Magrath G. Alternative diets to the classical ketogenic diet—Can we be more liberal? Epilepsy Res. 2012;100:278–285. doi: 10.1016/j.eplepsyres.2012.06.007.
    1. Sharma S., Sankhyan N., Gulati S., Agarwala A. Use of the modified atkins diet for treatment of refractory childhood epilepsy: A randomized controlled trial. Epilepsia. 2013;54:481–486. doi: 10.1111/epi.12069.
    1. Kossoff E.H., Cervenka M.C., Henry B.J., Haney C.A., Turner Z. A decade of the modified Atkins diet (2003–2013): Results, insights, and future directions. Epilepsy Behav. 2013;29:437–442. doi: 10.1016/j.yebeh.2013.09.032.
    1. Muzykewicz D.A., Lyczkowski D.A., Memon N., Conant K.D., Pfeifer H.H., Thiele E.A. Efficacy, safety, and tolerability of the low glycemic index treatment in pediatric epilepsy. Epilepsia. 2009;50:1118–1126. doi: 10.1111/j.1528-1167.2008.01959.x.
    1. Paoli A., Canato M., Toniolo L., Bargossi A.M., Neri M., Mediati M., Alesso D., Sanna G., Grimaldi K.A., Fazzari A.L., et al. The ketogenic diet: An underappreciated therapeutic option? La Clinica Terapeutica. 2011;162:e145–e153.
    1. Paoli A., Tinsley G., Bianco A., Moro T. The influence of meal frequency and timing on health in humans: The role of fasting. Nutrients. 2019;11:719. doi: 10.3390/nu11040719.
    1. Fukao T., Lopaschuk G.D., Mitchell G.A. Pathways and control of ketone body metabolism: On the fringe of lipid biochemistry. Prostaglandins Leukot. Essent. Fat. Acids. 2004;70:243–251. doi: 10.1016/j.plefa.2003.11.001.
    1. Dhillon K.K., Gupta S. Biochemistry, Ketogenesis. Statpearls; Treasure Island, FL, USA: 2019.
    1. Newell C., Bomhof M.R., Reimer R.A., Hittel D.S., Rho J.M., Shearer J. Ketogenic diet modifies the gut microbiota in a murine model of autism spectrum disorder. Mol. Autism. 2016;7:37. doi: 10.1186/s13229-016-0099-3.
    1. Xie G., Zhou Q., Qiu C.Z., Dai W.K., Wang H.P., Li Y.H., Liao J.X., Lu X.G., Lin S.F., Ye J.H., et al. Ketogenic diet poses a significant effect on imbalanced gut microbiota in infants with refractory epilepsy. World J. Gastroenterol. 2017;23:6164–6171. doi: 10.3748/wjg.v23.i33.6164.
    1. Zhang Y., Zhou S., Zhou Y., Yu L., Zhang L., Wang Y. Altered gut microbiome composition in children with refractory epilepsy after ketogenic diet. Epilepsy Res. 2018;145:163–168. doi: 10.1016/j.eplepsyres.2018.06.015.
    1. Lindefeldt M., Eng A., Darban H., Bjerkner A., Zetterstrom C.K., Allander T., Andersson B., Borenstein E., Dahlin M., Prast-Nielsen S. The ketogenic diet influences taxonomic and functional composition of the gut microbiota in children with severe epilepsy. npj Biofilms Microbiomes. 2019;5:5. doi: 10.1038/s41522-018-0073-2.
    1. Whitfield J.B. γ glutamyl transferase. Crit. Rev. Clin. Lab. Sci. 2001;38:263–355. doi: 10.1080/20014091084227.
    1. Pica A., Chi M.C., Chen Y.Y., d’Ischia M., Lin L.L., Merlino A. The maturation mechanism of γ-glutamyl transpeptidases: Insights from the crystal structure of a precursor mimic of the enzyme from bacillus licheniformis and from site-directed mutagenesis studies. Biochim. Biophys. Acta. 2016;1864:195–203. doi: 10.1016/j.bbapap.2015.10.006.
    1. Hertz L. The glutamate-glutamine (gaba) cycle: Importance of late postnatal development and potential reciprocal interactions between biosynthesis and degradation. Front. Endocrinol. (Lausanne) 2013;4:59. doi: 10.3389/fendo.2013.00059.
    1. Arumugam M., Raes J., Pelletier E., Le Paslier D., Yamada T., Mende D.R., Fernandes G.R., Tap J., Bruls T., Batto J.M., et al. Enterotypes of the human gut microbiome. Nature. 2011;473:174–180. doi: 10.1038/nature09944.
    1. Devkota S., Wang Y., Musch M.W., Leone V., Fehlner-Peach H., Nadimpalli A., Antonopoulos D.A., Jabri B., Chang E.B. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in IL-10−/− mice. Nature. 2012;487:104–108. doi: 10.1038/nature11225.
    1. O’Callaghan A., van Sinderen D. Bifidobacteria and their role as members of the human gut microbiota. Front. Microbiol. 2016;7:925. doi: 10.3389/fmicb.2016.00925.
    1. Graham L.C., Harder J.M., Soto I., de Vries W.N., John S.W., Howell G.R. Chronic consumption of a western diet induces robust glial activation in aging mice and in a mouse model of alzheimer’s disease. Sci. Rep. 2016;6:21568. doi: 10.1038/srep21568.
    1. Wolters M., Ahrens J., Romani-Perez M., Watkins C., Sanz Y., Benitez-Paez A., Stanton C., Gunther K. Dietary fat, the gut microbiota, and metabolic health—A systematic review conducted within the mynewgut project. Clin. Nutr. 2018 doi: 10.1016/j.clnu.2018.12.024.
    1. Cao Y., Fanning S., Proos S., Jordan K., Srikumar S. A review on the applications of next generation sequencing technologies as applied to food-related microbiome studies. Front. Microbiol. 2017;8:1829. doi: 10.3389/fmicb.2017.01829.
    1. Wan Y., Wang F., Yuan J., Li J., Jiang D., Zhang J., Li H., Wang R., Tang J., Huang T., et al. Effects of dietary fat on gut microbiota and faecal metabolites, and their relationship with cardiometabolic risk factors: A 6-month randomised controlled-feeding trial. Gut. 2019;68:1417–1429. doi: 10.1136/gutjnl-2018-317609.
    1. Isaac D.M., Alzaben A.S., Mazurak V.C., Yap J., Wizzard P.R., Nation P.N., Zhao Y.Y., Curtis J.M., Sergi C., Wales P.W., et al. Mixed lipid, fish oil and soybean oil parenteral lipids impact cholestasis, hepatic phytosterol and lipid composition. J. Pediatr. Gastroenterol. Nutr. 2019;68:861–867. doi: 10.1097/MPG.0000000000002313.
    1. Jang H., Park K. Omega-3 and omega-6 polyunsaturated fatty acids and metabolic syndrome: A systematic review and meta-analysis. Clin. Nutr. 2019 doi: 10.1016/j.clnu.2019.03.032.
    1. Noori N., Dukkipati R., Kovesdy C.P., Sim J.J., Feroze U., Murali S.B., Bross R., Benner D., Kopple J.D., Kalantar-Zadeh K. Dietary omega-3 fatty acid, ratio of omega-6 to omega-3 intake, inflammation, and survival in long-term hemodialysis patients. Am. J. Kidney Dis. 2011;58:248–256. doi: 10.1053/j.ajkd.2011.03.017.
    1. Lee H.J., Han Y.M., An J.M., Kang E.A., Park Y.J., Cha J.Y., Hahm K.B. Role of omega-3 polyunsaturated fatty acids in preventing gastrointestinal cancers: Current status and future perspectives. Expert Rev. Anticancer. 2018;18:1189–1203. doi: 10.1080/14737140.2018.1524299.
    1. Watson H., Mitra S., Croden F.C., Taylor M., Wood H.M., Perry S.L., Spencer J.A., Quirke P., Toogood G.J., Lawton C.L., et al. A randomised trial of the effect of omega-3 polyunsaturated fatty acid supplements on the human intestinal microbiota. Gut. 2018;67:1974–1983. doi: 10.1136/gutjnl-2017-314968.
    1. Bidu C., Escoula Q., Bellenger S., Spor A., Galan M., Geissler A., Bouchot A., Dardevet D., Morio B., Cani P.D., et al. The transplantation of ω3 PUFA-altered gut microbiota of FAT-1 mice to wild-type littermates prevents obesity and associated metabolic disorders. Diabetes. 2018;67:1512–1523. doi: 10.2337/db17-1488.
    1. Nettleton J.E., Reimer R.A., Shearer J. Reshaping the gut microbiota: Impact of low calorie sweeteners and the link to insulin resistance? Physiol. Behav. 2016;164:488–493. doi: 10.1016/j.physbeh.2016.04.029.
    1. Wang Q.P., Browman D., Herzog H., Neely G.G. Non-nutritive sweeteners possess a bacteriostatic effect and alter gut microbiota in mice. PLoS ONE. 2018;13:e0199080. doi: 10.1371/journal.pone.0199080.
    1. Azad M.B., Abou-Setta A.M., Chauhan B.F., Rabbani R., Lys J., Copstein L., Mann A., Jeyaraman M.M., Reid A.E., Fiander M., et al. Nonnutritive sweeteners and cardiometabolic health: A systematic review and meta-analysis of randomized controlled trials and prospective cohort studies. CMAJ. 2017;189:E929–E939. doi: 10.1503/cmaj.161390.
    1. Suez J., Korem T., Zeevi D., Zilberman-Schapira G., Thaiss C.A., Maza O., Israeli D., Zmora N., Gilad S., Weinberger A., et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014;514:181–186. doi: 10.1038/nature13793.
    1. Anton S.D., Martin C.K., Han H., Coulon S., Cefalu W.T., Geiselman P., Williamson D.A. Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels. Appetite. 2010;55:37–43. doi: 10.1016/j.appet.2010.03.009.
    1. Sharma N., Mogra R., Upadhyay B. Effect of stevia extract intervention on lipid profile. Stud. Ethno-Med. 2009;3:137–140. doi: 10.1080/09735070.2009.11886351.
    1. Samuel P., Ayoob K.T., Magnuson B.A., Wolwer-Rieck U., Jeppesen P.B., Rogers P.J., Rowland I., Mathews R. Stevia leaf to stevia sweetener: Exploring its science, benefits, and future potential. J. Nutr. 2018;148:1186S–1205S. doi: 10.1093/jn/nxy102.
    1. Pepino M.Y. Metabolic effects of non-nutritive sweeteners. Physiol. Behav. 2015;152:450–455. doi: 10.1016/j.physbeh.2015.06.024.
    1. Perrier J.D., Mihalov J.J., Carlson S.J. Fda regulatory approach to steviol glycosides. Food Chem. Toxicol. 2018;122:132–142. doi: 10.1016/j.fct.2018.09.062.
    1. Finamore A., Roselli M., Donini L., Brasili D.E., Rami R., Carnevali P., Mistura L., Pinto A., Giusti A., Mengheri E. Supplementation with Bifidobacterium longum Bar33 and lactobacillus helveticus bar13 mixture improves immunity in elderly humans (over 75 years) and aged mice. Nutrition. 2019;63–64:184–192. doi: 10.1016/j.nut.2019.02.005.
    1. Bagheri S., Heydari A., Alinaghipour A., Salami M. Effect of probiotic supplementation on seizure activity and cognitive performance in PTZ-induced chemical kindling. Epilepsy Behav. 2019;95:43–50. doi: 10.1016/j.yebeh.2019.03.038.
    1. Davani-Davari D., Negahdaripour M., Karimzadeh I., Seifan M., Mohkam M., Masoumi S.J., Berenjian A., Ghasemi Y. Prebiotics: Definition, types, sources, mechanisms, and clinical applications. Foods. 2019;8:92. doi: 10.3390/foods8030092.
    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. Env. Microbiol. 2007;9:1101–1111. doi: 10.1111/j.1462-2920.2007.01281.x.
    1. Quigley E.M.M. Prebiotics and probiotics in digestive health. Clin. Gastroenterol. Hepatol. 2019;17:333–344. doi: 10.1016/j.cgh.2018.09.028.
    1. Nath A., Haktanirlar G., Varga A., Molnar M.A., Albert K., Galambos I., Koris A., Vatai G. Biological activities of lactose-derived prebiotics and symbiotic with probiotics on gastrointestinal system. Medicina (Kaunas) 2018;54:18. doi: 10.3390/medicina54020018.
    1. Valdes A.M., Walter J., Segal E., Spector T.D. Role of the gut microbiota in nutrition and health. BMJ. 2018;361:k2179. doi: 10.1136/bmj.k2179.
    1. Marco M.L., Heeney D., Binda S., Cifelli C.J., Cotter P.D., Foligne B., Ganzle M., Kort R., Pasin G., Pihlanto A., et al. Health benefits of fermented foods: Microbiota and beyond. Curr. Opin. Biotechnol. 2017;44:94–102. doi: 10.1016/j.copbio.2016.11.010.
    1. Borresen E.C., Henderson A.J., Kumar A., Weir T.L., Ryan E.P. Fermented foods: Patented approaches and formulations for nutritional supplementation and health promotion. Recent Pat. Food Nutr. Agric. 2012;4:134–140. doi: 10.2174/2212798411204020134.
    1. Dong Y., Xu M., Chen L., Bhochhibhoya A. Probiotic foods and supplements interventions for metabolic syndromes: A systematic review and meta-analysis of recent clinical trials. Ann. Nutr. Metab. 2019;74:224–241. doi: 10.1159/000499028.
    1. Sairanen U., Piirainen L., Grasten S., Tompuri T., Matto J., Saarela M., Korpela R. The effect of probiotic fermented milk and inulin on the functions and microecology of the intestine. J. Dairy Res. 2007;74:367–373. doi: 10.1017/S0022029907002713.
    1. Yoon H., Park Y.S., Lee D.H., Seo J.G., Shin C.M., Kim N. Effect of administering a multi-species probiotic mixture on the changes in fecal microbiota and symptoms of irritable bowel syndrome: A randomized, double-blind, placebo-controlled trial. J. Clin. Biochem. Nutr. 2015;57:129–134. doi: 10.3164/jcbn.15-14.
    1. Yang S.J., Lee J.E., Lim S.M., Kim Y.J., Lee N.K., Paik H.D. Antioxidant and immune-enhancing effects of probiotic Lactobacillus plantarum 200655 isolated from kimchi. Food Sci. Biotechnol. 2019;28:491–499. doi: 10.1007/s10068-018-0473-3.
    1. Shiby V.K., Mishra H.N. Fermented milks and milk products as functional foods—A review. Crit. Rev. Food Sci. Nutr. 2013;53:482–496. doi: 10.1080/10408398.2010.547398.
    1. Matsumoto K., Takada T., Shimizu K., Moriyama K., Kawakami K., Hirano K., Kajimoto O., Nomoto K. Effects of a probiotic fermented milk beverage containing Lactobacillus casei strain shirota on defecation frequency, intestinal microbiota, and the intestinal environment of healthy individuals with soft stools. J. Biosci. Bioeng. 2010;110:547–552. doi: 10.1016/j.jbiosc.2010.05.016.
    1. Bell V., Ferrao J., Pimentel L., Pintado M., Fernandes T. One health, fermented foods, and gut microbiota. Foods. 2018;7:195. doi: 10.3390/foods7120195.
    1. Singh R.K., Chang H.W., Yan D., Lee K.M., Ucmak D., Wong K., Abrouk M., Farahnik B., Nakamura M., Zhu T.H., et al. Influence of diet on the gut microbiome and implications for human health. J. Transl. Med. 2017;15:73. doi: 10.1186/s12967-017-1175-y.
    1. Milani C., Duranti S., Napoli S., Alessandri G., Mancabelli L., Anzalone R., Longhi G., Viappiani A., Mangifesta M., Lugli G.A., et al. Colonization of the human gut by bovine bacteria present in parmesan cheese. Nat. Commun. 2019;10:1286. doi: 10.1038/s41467-019-09303-w.
    1. Paoli A., Bianco A., Grimaldi K.A. The ketogenic diet and sport: A possible marriage? Exerc. Sport Sci. Rev. 2015;43:153–162. doi: 10.1249/JES.0000000000000050.
    1. Nakatani A., Li X., Miyamoto J., Igarashi M., Watanabe H., Sutou A., Watanabe K., Motoyama T., Tachibana N., Kohno M., et al. Dietary mung bean protein reduces high-fat diet-induced weight gain by modulating host bile acid metabolism in a gut microbiota-dependent manner. Biochem. Biophys. Res. Commun. 2018;501:955–961. doi: 10.1016/j.bbrc.2018.05.090.
    1. Meddah A.T., Yazourh A., Desmet I., Risbourg B., Verstraete W., Romond M.B. The regulatory effects of whey retentate from bifidobacteria fermented milk on the microbiota of the simulator of the human intestinal microbial ecosystem (SHIME) J. Appl. Microbiol. 2001;91:1110–1117. doi: 10.1046/j.1365-2672.2001.01482.x.
    1. Swiatecka D., Narbad A., Ridgway K.P., Kostyra H. The study on the impact of glycated pea proteins on human intestinal bacteria. Int. J. Food Microbiol. 2011;145:267–272.
    1. Mu C., Yang Y., Luo Z., Guan L., Zhu W. The colonic microbiome and epithelial transcriptome are altered in rats fed a high-protein diet compared with a normal-protein diet. J. Nutr. 2016;146:474–483. doi: 10.3945/jn.115.223990.
    1. Zhu Y., Lin X., Zhao F., Shi X., Li H., Li Y., Zhu W., Xu X., Li C., Zhou G. Erratum: Meat, dairy and plant proteins alter bacterial composition of rat gut bacteria. Sci. Rep. 2015;5:16546. doi: 10.1038/srep16546.
    1. Griffin N.W., Ahern P.P., Cheng J., Heath A.C., Ilkayeva O., Newgard C.B., Fontana L., Gordon J.I. Prior dietary practices and connections to a human gut microbial metacommunity alter responses to diet interventions. Cell Host Microbe. 2017;21:84–96. doi: 10.1016/j.chom.2016.12.006.
    1. Healey G.R., Murphy R., Brough L., Butts C.A., Coad J. Interindividual variability in gut microbiota and host response to dietary interventions. Nutr. Rev. 2017;75:1059–1080. doi: 10.1093/nutrit/nux062.
    1. Turroni F., Milani C., Duranti S., Mancabelli L., Mangifesta M., Viappiani A., Lugli G.A., Ferrario C., Gioiosa L., Ferrarini A., et al. Deciphering bifidobacterial-mediated metabolic interactions and their impact on gut microbiota by a multi-omics approach. ISME J. 2016;10:1656–1668. doi: 10.1038/ismej.2015.236.
    1. Integrative HMP (iHMP) Research Network Consortium The integrative human microbiome project: Dynamic analysis of microbiome-host omics profiles during periods of human health and disease. Cell Host Microbe. 2014;16:276–289. doi: 10.1016/j.chom.2014.08.014.
    1. Zeevi D., Korem T., Zmora N., Israeli D., Rothschild D., Weinberger A., Ben-Yacov O., Lador D., Avnit-Sagi T., Lotan-Pompan M., et al. Personalized nutrition by prediction of glycemic responses. Cell. 2015;163:1079–1094. doi: 10.1016/j.cell.2015.11.001.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe