Gut microbiota; Obesity; Prebiotic; Clinical trial; Cognition
Abstract :
[en] Background and aims
Metabolic and behavioural diseases, which are often related to obesity, have been associated to alterations of the gut microbiota considered as an interesting therapeutic target. We have analyzed in a cohort of obese patients treated with prebiotic inulin versus placebo the potential link between gut microbiota changes occurring upon intervention and their effect on psychological parameters (mood and cognition).
Methods
A randomized, single-blinded, multicentric, placebo-controlled trial was conducted in 106 obese patients assigned to two groups: prebiotic versus placebo, who received respectively 16 g/d of native inulin or maltodextrin combined with dietary advice to consume inulin-rich or -poor vegetables for 3 months as well as to restrict caloric intake. Anthropometric measurements, food intake, psychological questionnaires, serum measures, and fecal microbiome sequencing were performed before and after the intervention.
Results
Inulin supplementation in obese subjects had moderate beneficial effect on emotional competence and cognitive flexibility. However, an exploratory analysis revealed that some patients exhibiting specific microbial signature -elevated Coprococcus levels at baseline- were more prone to benefit from prebiotic supplementation in terms of mood. Positive responders toward inulin intervention in term of mood also displayed worse metabolic and inflammatory profiles at baseline (increased levels of IL-8, insulin resistance and adiposity).
Conclusion
This study shows that inulin intake can be helpful to improve mood in obese subjects exhibiting a specific microbial profile. The present work highlights some microbial, metabolic and inflammatory features (IL-8, insulin resistance) which can predict or mediate the beneficial effects of inulin on behaviour in obesity.
Bindelle, Jérôme ; Université de Liège - ULiège > Département GxABT > Ingénierie des productions animales et nutrition
PAQUOT, Nicolas ; Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de diabétologie, nutrition, maladies métaboliques
Arnoriaga-Rodríguez, M., Mayneris-Perxachs, J., Burokas, A., Contreras-Rodríguez, O., Blasco, G., Coll, C., Biarnés, C., Miranda-Olivos, R., Latorre, J., Moreno-Navarrete, J.-M., Castells-Nobau, A., Sabater, M., Palomo-Buitrago, M.E., Puig, J., Pedraza, S., Gich, J., Pérez-Brocal, V., Ricart, W., Moya, A., Fernández-Real, X., Ramió-Torrentà, L., Pamplona, R., Sol, J., Jové, M., Portero-Otin, M., Maldonado, R., Fernández-Real, J.M., obesity impairs short-term and working memory through gut microbial metabolism of aromatic amino acids. Cell Metab. 32 (2020), 548–560.e7, 10.1016/j.cmet.2020.09.002.
Athauda, D., Maclagan, K., Budnik, N., Zampedri, L., Hibbert, S., Skene, S.S., Chowdhury, K., Aviles-Olmos, I., Limousin, P., Foltynie, T., What effects might exenatide have on non-motor symptoms in Parkinson's Disease: a post hoc analysis. J. Parkinsons Dis. 8 (2018), 247–258, 10.3233/JPD-181329.
Azpiroz, F., Dubray, C., Bernalier-Donadille, A., Cardot, J.-M., Accarino, A., Serra, J., Wagner, A., Respondek, F., Dapoigny, M., Effects of scFOS on the composition of fecal microbiota and anxiety in patients with irritable bowel syndrome: a randomized, double blind, placebo controlled study. Neurogastroenterol. Motil., 29, 2017, 10.1111/nmo.12911.
Bazinet, R.P., Layé, S., Polyunsaturated fatty acids and their metabolites in brain function and disease. Nat. Rev. Neurosci. 15 (2014), 771–785, 10.1038/nrn3820.
Belenguer, Alvaro, et al. Two routes of metabolic cross-feeding between Bifidobacterium adolescentis and butyrate-producing anaerobes from the human gut. Appl. Environ. Microbiol., 2006, 10.1128/AEM.72.5.3593-3599.2006.
Berding, K., Long-Smith, C.M., Carbia, C., Bastiaanssen, T.F.S., van de Wouw, M., Wiley, N., Strain, C.R., Fouhy, F., Stanton, C., Cryan, J.F., Dinan, T.G., A specific dietary fibre supplementation improves cognitive performance-an exploratory randomised, placebo-controlled, crossover study. Psychopharmacology, 2020, 10.1007/s00213-020-05665-y.
Boehme, M., van de Wouw, M., Bastiaanssen, T.F.S., Olavarría-Ramírez, L., Lyons, K., Fouhy, F., Golubeva, A.V., Moloney, G.M., Minuto, C., Sandhu, K.V., Scott, K.A., Clarke, G., Stanton, C., Dinan, T.G., Schellekens, H., Cryan, J.F., Mid-life microbiota crises: middle age is associated with pervasive neuroimmune alterations that are reversed by targeting the gut microbiome. Mol. Psychiatry, 2019, 10.1038/s41380-019-0425-1.
Brasseur, S., Grégoire, J., Bourdu, R., Mikolajczak, M., The Profile of Emotional Competence (PEC): development and validation of a self-reported measure that fits dimensions of emotional competence theory. PLoS ONE, 8, 2013, e62635, 10.1371/journal.pone.0062635.
Bruce-Keller, A.J., Salbaum, J.M., Luo, M., Blanchard, E., Taylor, C.M., Welsh, D.A., Berthoud, H.-R., Obese-type gut microbiota induce neurobehavioral changes in the absence of obesity. Biol. Psychiatry 77 (2015), 607–615, 10.1016/j.biopsych.2014.07.012.
Bruun, J.M., Pedersen, S.B., Kristensen, K., Richelsen, B., Opposite regulation of interleukin-8 and tumor necrosis factor-alpha by weight loss. Obes. Res. 10 (2002), 499–506, 10.1038/oby.2002.68.
Bruun, J.M., Verdich, C., Toubro, S., Astrup, A., Richelsen, B., Association between measures of insulin sensitivity and circulating levels of interleukin-8, interleukin-6 and tumor necrosis factor-alpha. Effect of weight loss in obese men. Eur. J. Endocrinol. 148 (2003), 535–542, 10.1530/eje.0.1480535.
Capuron, L., Lasselin, J., Castanon, N., Role of adiposity-driven inflammation in depressive morbidity. Neuropsychopharmacology 42 (2017), 115–128, 10.1038/npp.2016.123.
Castaner, O., Goday, A., Park, Y.-M., Lee, S.-H., Magkos, F., Shiow, S.-A.-T.-E., Schröder, H., The gut microbiome profile in obesity: a systematic review. Int. J. Endocrinol., 2018, 2018, 10.1155/2018/4095789.
Chambers, E.S., Byrne, C.S., Morrison, D.J., Murphy, K.G., Preston, T., Tedford, C., Garcia-Perez, I., Fountana, S., Serrano-Contreras, J.I., Holmes, E., Reynolds, C.J., Roberts, J.F., Boyton, R.J., Altmann, D.M., McDonald, J.A.K., Marchesi, J.R., Akbar, A.N., Riddell, N.E., Wallis, G.A., Frost, G.S., Dietary supplementation with inulin-propionate ester or inulin improves insulin sensitivity in adults with overweight and obesity with distinct effects on the gut microbiota, plasma metabolome and systemic inflammatory responses: a randomised cross-over trial. Gut 68 (2019), 1430–1438, 10.1136/gutjnl-2019-318424.
Chepenik, L.G., Cornew, L.A., Farah, M.J., The influence of sad mood on cognition. Emotion 7 (2007), 802–811, 10.1037/1528-3542.7.4.802.
Chianese, R., Coccurello, R., Viggiano, A., Scafuro, M., Fiore, M., Coppola, G., Operto, F.F., Fasano, S., Layé, S., Pierantoni, R., Meccariello, R., Impact of dietary fats on brain functions. Curr. Neuropharmacol. 16 (2018), 1059–1085, 10.2174/1570159X15666171017102547.
Childs, C.E., Röytiö, H., Alhoniemi, E., Fekete, A.A., Forssten, S.D., Hudjec, N., Lim, Y.N., Steger, C.J., Yaqoob, P., Tuohy, K.M., Rastall, R.A., Ouwehand, A.C., Gibson, G.R., Xylo-oligosaccharides alone or in synbiotic combination with Bifidobacterium animalis subsp. lactis induce bifidogenesis and modulate markers of immune function in healthy adults: a double-blind, placebo-controlled, randomised, factorial cross-over study. Br. J. Nutr. 111 (2014), 1945–1956, 10.1017/S0007114513004261.
Costabile, A., Kolida, S., Klinder, A., Gietl, E., Bäuerlein, M., Frohberg, C., Landschütze, V., Gibson, G.R., A double-blind, placebo-controlled, cross-over study to establish the bifidogenic effect of a very-long-chain inulin extracted from globe artichoke (Cynara scolymus) in healthy human subjects. Br. J. Nutr. 104 (2010), 1007–1017, 10.1017/S0007114510001571.
Cryan, J.F., O'Riordan, K.J., Cowan, C.S.M., Sandhu, K.V., Bastiaanssen, T.F.S., Boehme, M., Codagnone, M.G., Cussotto, S., Fulling, C., Golubeva, A.V., Guzzetta, K.E., Jaggar, M., Long-Smith, C.M., Lyte, J.M., Martin, J.A., Molinero-Perez, A., Moloney, G., Morelli, E., Morillas, E., O'Connor, R., Cruz-Pereira, J.S., Peterson, V.L., Rea, K., Ritz, N.L., Sherwin, E., Spichak, S., Teichman, E.M., van de Wouw, M., Ventura-Silva, A.P., Wallace-Fitzsimons, S.E., Hyland, N., Clarke, G., Dinan, T.G., The microbiota-gut-brain axis. Physiol. Rev. 99 (2019), 1877–2013, 10.1152/physrev.00018.2018.
de Preter, V., Vanhoutte, T., Huys, G., Swings, J., Rutgeerts, P., Verbeke, K., Baseline microbiota activity and initial bifidobacteria counts influence responses to prebiotic dosing in healthy subjects. Aliment. Pharmacol. Ther. 27 (2008), 504–513, 10.1111/j.1365-2036.2007.03588.x.
Delzenne, N.M., Rodriguez, J., Olivares, M., Neyrinck, A.M., Microbiome response to diet: focus on obesity and related diseases. Rev. Endocr. Metab. Disord. 21 (2020), 369–380, 10.1007/s11154-020-09572-7.
Desmedt, O., Broers, V.J.V., Zamariola, G., Pachikian, B., Delzenne, N., Luminet, O., Effects of prebiotics on affect and cognition in human intervention studies. Nutr. Rev. 77 (2019), 81–95, 10.1093/nutrit/nuy052.
Dewulf, E.M., Cani, P.D., Claus, S.P., Fuentes, S., Puylaert, P.G.B., Neyrinck, A.M., Bindels, L.B., de Vos, W.M., Gibson, G.R., Thissen, J.-P., Delzenne, N.M., Insight into the prebiotic concept: lessons from an exploratory, double blind intervention study with inulin-type fructans in obese women. Gut 62 (2013), 1112–1121, 10.1136/gutjnl-2012-303304.
Diener, E., Wirtz, D., Tov, W., Kim-Prieto, C., Choi, D., Oishi, S., Biswas-Diener, R., New well-being measures: short scales to assess flourishing and positive and negative feelings. Soc. Indic. Res. 97 (2010), 143–156, 10.1007/s11205-009-9493-y.
Driessen, E., Hollon, S.D., Cognitive behavioral therapy for mood disorders: efficacy, moderators and mediators. Psychiatr. Clin. North Am. 33 (2010), 537–555, 10.1016/j.psc.2010.04.005.
Duncan, Sylvia H, et al. Contribution of acetate to butyrate formation by human faecal bacteria. Br. J. Nutr., 2004, 10.1079/BJN20041150.
Gibson, G.R., Hutkins, R., Sanders, M.E., Prescott, S.L., Reimer, R.A., Salminen, S.J., Scott, K., Stanton, C., Swanson, K.S., Cani, P.D., Verbeke, K., Reid, G., Expert consensus document: the International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat. Rev. Gastroenterol. Hepatol. 14 (2017), 491–502, 10.1038/nrgastro.2017.75.
Gloor, G.B., Macklaim, J.M., Pawlowsky-Glahn, V., Egozcue, J.J., Microbiome datasets are compositional: and this is not optional. Front. Microbiol., 8, 2017, 10.3389/fmicb.2017.02224.
Gotlib, I.H., Joormann, J., Cognition and depression: current status and future directions. Annu. Rev. Clin. Psychol. 6 (2010), 285–312, 10.1146/annurev.clinpsy.121208.131305.
Healey, G., Murphy, R., Butts, C., Brough, L., Whelan, K., Coad, J., Habitual dietary fibre intake influences gut microbiota response to an inulin-type fructan prebiotic: a randomised, double-blind, placebo-controlled, cross-over, human intervention study. Br. J. Nutr. 119 (2018), 176–189, 10.1017/S0007114517003440.
Hiel, S., Gianfrancesco, M.A., Rodriguez, J., Portheault, D., Leyrolle, Q., Bindels, L.B., da Silveira, G., Cauduro, C., Mulders, M.D.G.H., Zamariola, G., Azzi, A.-S., Kalala, G., Pachikian, B.D., Amadieu, C., Neyrinck, A.M., Loumaye, A., Cani, P.D., Lanthier, N., Trefois, P., Klein, O., Luminet, O., Bindelle, J., Paquot, N., Cnop, M., Thissen, J.-P., Delzenne, N.M., Link between gut microbiota and health outcomes in inulin -treated obese patients: Lessons from the Food4Gut multicenter randomized placebo-controlled trial. Clin. Nutr., 2020, 10.1016/j.clnu.2020.04.005.
Hoffman, J.D., Yanckello, L.M., Chlipala, G., Hammond, T.C., McCulloch, S.D., Parikh, I., Sun, S., Morganti, J.M., Green, S.J., Lin, A.-L., Dietary inulin alters the gut microbiome, enhances systemic metabolism and reduces neuroinflammation in an APOE4 mouse model. PLoS ONE, 14, 2019, e0221828, 10.1371/journal.pone.0221828.
Joormann, J., Gotlib, I.H., Emotion regulation in depression: relation to cognitive inhibition. Cogn. Emot. 24 (2010), 281–298, 10.1080/02699930903407948.
Keshavarzian, A., Green, S.J., Engen, P.A., Voigt, R.M., Naqib, A., Forsyth, C.B., Mutlu, E., Shannon, K.M., Colonic bacterial composition in Parkinson's disease. Mov. Disord. 30 (2015), 1351–1360, 10.1002/mds.26307.
Kim, K.N., Yao, Y., Ju, S.Y., Short chain fatty acids and fecal microbiota abundance in humans with obesity: a systematic review and meta-analysis. Nutrients, 11, 2019, 2512, 10.3390/nu11102512.
Kloiber, S., Ising, M., Reppermund, S., Horstmann, S., Dose, T., Majer, M., Zihl, J., Pfister, H., Unschuld, P.G., Holsboer, F., Lucae, S., Overweight and obesity affect treatment response in major depression. Biol. Psychiatry 62 (2007), 321–326, 10.1016/j.biopsych.2006.10.001.
Kolida, S., Meyer, D., Gibson, G.R., A double-blind placebo-controlled study to establish the bifidogenic dose of inulin in healthy humans. Eur. J. Clin. Nutr. 61 (2007), 1189–1195, 10.1038/sj.ejcn.1602636.
Luppino, F.S., de Wit, L.M., Bouvy, P.F., Stijnen, T., Cuijpers, P., Penninx, B.W.J.H., Zitman, F.G., Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies. Arch. Gen. Psychiatry 67 (2010), 220–229, 10.1001/archgenpsychiatry.2010.2.
Manchishi, S.M., Cui, R.J., Zou, X.H., Cheng, Z.Q., Li, B. jin., Effect of caloric restriction on depression. J Cell Mol Med 22 (2018), 2528–2535, 10.1111/jcmm.13418.
Moens, F., De Vuyst, L., Inulin-type fructan degradation capacity of Clostridium cluster IV and XIVa butyrate-producing colon bacteria and their associated metabolic outcomes. Benef Microbes 8 (2017), 473–490, 10.3920/BM2016.0142.
Nicolucci, A.C., Hume, M.P., Martínez, I., Mayengbam, S., Walter, J., Reimer, R.A., Prebiotics reduce body fat and alter intestinal microbiota in children who are overweight or with obesity. Gastroenterology 153 (2017), 711–722, 10.1053/j.gastro.2017.05.055.
Nyberg, S.T., Batty, G.D., Pentti, J., Virtanen, M., Alfredsson, L., Fransson, E.I., Goldberg, M., Heikkilä, K., Jokela, M., Knutsson, A., Koskenvuo, M., Lallukka, T., Leineweber, C., Lindbohm, J.V., Madsen, I.E.H., Magnusson Hanson, L.L., Nordin, M., Oksanen, T., Pietiläinen, O., Rahkonen, O., Rugulies, R., Shipley, M.J., Stenholm, S., Suominen, S., Theorell, T., Vahtera, J., Westerholm, P.J.M., Westerlund, H., Zins, M., Hamer, M., Singh-Manoux, A., Bell, J.A., Ferrie, J.E., Kivimäki, M., Obesity and loss of disease-free years owing to major non-communicable diseases: a multicohort study. Lancet Public Health 3 (2018), e490–e497, 10.1016/S2468-2667(18)30139-7.
Okon-Singer, H., Hendler, T., Pessoa, L., Shackman, A.J., The neurobiology of emotion–cognition interactions: fundamental questions and strategies for future research. Front. Hum. Neurosci., 9, 2015, 10.3389/fnhum.2015.00058.
Olivares, M., Neyrinck, A.M., Pötgens, S.A., Beaumont, M., Salazar, N., Cani, P.D., Bindels, L.B., Delzenne, N.M., The DPP-4 inhibitor vildagliptin impacts the gut microbiota and prevents disruption of intestinal homeostasis induced by a Western diet in mice. Diabetologia 61 (2018), 1838–1848, 10.1007/s00125-018-4647-6.
Pinto-Sanchez, M.I., Hall, G.B., Ghajar, K., Nardelli, A., Bolino, C., Lau, J.T., Martin, F.-P., Cominetti, O., Welsh, C., Rieder, A., Traynor, J., Gregory, C., De Palma, G., Pigrau, M., Ford, A.C., Macri, J., Berger, B., Bergonzelli, G., Surette, M.G., Collins, S.M., Moayyedi, P., Bercik, P., Probiotic Bifidobacterium longum NCC3001 reduces depression scores and alters brain activity: a pilot study in patients with irritable bowel syndrome. Gastroenterology 153 (2017), 448–459.e8, 10.1053/j.gastro.2017.05.003.
Pötgens, S.A., Brossel, H., Sboarina, M., Catry, E., Cani, P.D., Neyrinck, A.M., Delzenne, N.M., Bindels, L.B., Klebsiella oxytoca expands in cancer cachexia and acts as a gut pathobiont contributing to intestinal dysfunction. Sci. Rep., 8, 2018, 12321, 10.1038/s41598-018-30569-5.
Reimer, R.A., Willis, H.J., Tunnicliffe, J.M., Park, H., Madsen, K.L., Soto-Vaca, A., Inulin-type fructans and whey protein both modulate appetite but only fructans alter gut microbiota in adults with overweight/obesity: a randomized controlled trial. Mol. Nutr. Food Res., 61, 2017, 10.1002/mnfr.201700484.
Rodriguez, J., Hiel, S., Delzenne, N.M., Metformin: old friend, new ways of action-implication of the gut microbiome?. Curr. Opin. Clin. Nutr. Metab. Care 21 (2018), 294–301, 10.1097/MCO.0000000000000468.
Rodriguez, J., Hiel, S., Neyrinck, A.M., Le Roy, T., Pötgens, S.A., Leyrolle, Q., Pachikian, B.D., Gianfrancesco, M.A., Cani, P.D., Paquot, N., Cnop, M., Lanthier, N., Thissen, J.-P., Bindels, L.B., Delzenne, N.M., Discovery of the gut microbial signature driving the efficacy of prebiotic intervention in obese patients. Gut, 2020, 10.1136/gutjnl-2019-319726.
Rogers, R.D., Monsell, S., Costs of a predictible switch between simple cognitive tasks. J. Exp. Psychol.: Gen. 124 (1995), 207–231, 10.1037/0096-3445.124.2.207.
Rossi, M., Corradini, C., Amaretti, A., Nicolini, M., Pompei, A., Zanoni, S., Matteuzzi, D., Fermentation of Fructooligosaccharides and Inulin by Bifidobacteria: a Comparative Study of Pure and Fecal Cultures. Appl. Environ. Microbiol. 71 (2005), 6150–6158, 10.1128/AEM.71.10.6150-6158.2005.
Schachter, J., Martel, J., Lin, C.-S., Chang, C.-J., Wu, T.-R., Lu, C.-C., Ko, Y.-F., Lai, H.-C., Ojcius, D.M., Young, J.D., Effects of obesity on depression: a role for inflammation and the gut microbiota. Brain Behav. Immun. 69 (2018), 1–8, 10.1016/j.bbi.2017.08.026.
Schmidt, K., Cowen, P.J., Harmer, C.J., Tzortzis, G., Errington, S., Burnet, P.W.J., Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers. Psychopharmacology 232 (2015), 1793–1801, 10.1007/s00213-014-3810-0.
Silk, D.B.A., Davis, A., Vulevic, J., Tzortzis, G., Gibson, G.R., Clinical trial: the effects of a trans-galactooligosaccharide prebiotic on faecal microbiota and symptoms in irritable bowel syndrome. Aliment. Pharmacol. Ther. 29 (2009), 508–518, 10.1111/j.1365-2036.2008.03911.x.
Slavin, J., Feirtag, J., Chicory inulin does not increase stool weight or speed up intestinal transit time in healthy male subjects. Food Funct. 2 (2011), 72–77, 10.1039/c0fo00101e.
Smith, A.P., Sutherland, D., Hewlett, P., An investigation of the acute effects of oligofructose-enriched inulin on subjective wellbeing, mood and cognitive performance. Nutrients 7 (2015), 8887–8896, 10.3390/nu7115441.
Steenbergen, L., Sellaro, R., van Hemert, S., Bosch, J.A., Colzato, L.S., A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain Behav. Immun. 48 (2015), 258–264, 10.1016/j.bbi.2015.04.003.
Stilling, R.M., van de Wouw, M., Clarke, G., Stanton, C., Dinan, T.G., Cryan, J.F., The neuropharmacology of butyrate: the bread and butter of the microbiota-gut-brain axis?. Neurochem. Int. 99 (2016), 110–132, 10.1016/j.neuint.2016.06.011.
Thingholm, L.B., Rühlemann, M.C., Koch, M., Fuqua, B., Laucke, G., Boehm, R., Bang, C., Franzosa, E.A., Hübenthal, M., Rahnavard, A., Frost, F., Lloyd-Price, J., Schirmer, M., Lusis, A.J., Vulpe, C.D., Lerch, M.M., Homuth, G., Kacprowski, T., Schmidt, C.O., Nöthlings, U., Karlsen, T.H., Lieb, W., Laudes, M., Franke, A., Huttenhower, C., Obese individuals with and without type 2 diabetes show different gut microbial functional capacity and composition. Cell Host Microbe 26 (2019), 252–264.e10, 10.1016/j.chom.2019.07.004.
Torres-Fuentes, C., Schellekens, H., Dinan, T.G., Cryan, J.F., The microbiota-gut-brain axis in obesity. Lancet Gastroenterol. Hepatol. 2 (2017), 747–756, 10.1016/S2468-1253(17)30147-4.
Valles-Colomer, M., Falony, G., Darzi, Y., Tigchelaar, E.F., Wang, J., Tito, R.Y., Schiweck, C., Kurilshikov, A., Joossens, M., Wijmenga, C., Claes, S., Van Oudenhove, L., Zhernakova, A., Vieira-Silva, S., Raes, J., The neuroactive potential of the human gut microbiota in quality of life and depression. Nat. Microbiol. 4 (2019), 623–632, 10.1038/s41564-018-0337-x.
van der Beek, C.M., Canfora, E.E., Kip, A.M., Gorissen, S.H.M., Olde Damink, S.W.M., van Eijk, H.M., Holst, J.J., Blaak, E.E., Dejong, C.H.C., Lenaerts, K., The prebiotic inulin improves substrate metabolism and promotes short-chain fatty acid production in overweight to obese men. Metab. Clin. Exp. 87 (2018), 25–35, 10.1016/j.metabol.2018.06.009.
Vandeputte, D., Falony, G., Vieira-Silva, S., Wang, J., Sailer, M., Theis, S., Verbeke, K., Raes, J., Prebiotic inulin-type fructans induce specific changes in the human gut microbiota. Gut 66 (2017), 1968–1974, 10.1136/gutjnl-2016-313271.
Watson, D., Clark, L.A., Tellegen, A., Development and validation of brief measures of positive and negative affect: the PANAS scales. J. Pers. Soc. Psychol. 54 (1988), 1063–1070, 10.1037//0022-3514.54.6.1063.
WHO, 2016. Obesity and overweight. < http://www.who.int/mediacentre/factsheets/fs311/en/>. - Recherche Google [WWW Document], n.d. URL < https://www.google.com/search?q=WHO%2C+2016.+Obesity+and+overweight.+%3Chttp%3A%2F%2Fwww.who.int%2Fmediacentre%2F+factsheets%2Ffs311%2Fen%2F%3E.&rlz=1C1GCEB_enBE839BE839&oq=WHO%2C+2016.+Obesity+and+overweight.+%3Chttp%3A%2F%2Fwww.who.int%2Fmediacentre%2F+factsheets%2Ffs311%2Fen%2F%3E.&aqs=chrome.69i57.592j0j7&sourceid=chrome&ie=UTF-8> (accessed 2.11.20).
