Volume 10 Supplement 1
Modulation of the gut microbiota by nutrients with prebiotic properties: consequences for host health in the context of obesity and metabolic syndrome
© Delzenne et al; licensee BioMed Central Ltd. 2011
Published: 30 August 2011
The gut microbiota is increasingly considered as a symbiotic partner for the maintenance of health. The homeostasis of the gut microbiota is dependent on host characteristics (age, gender, genetic background…), environmental conditions (stress, drugs, gastrointestinal surgery, infectious and toxic agents…). Moreover, it is dependent on the day-to-day dietary changes. Experimental data in animals, but also observational studies in obese patients, suggest that the composition of the gut microbiota is a factor characterizing obese versus lean individuals, diabetic versus non diabetic patients, or patients presenting hepatic diseases such as non alcoholic steatohepatitis. Interestingly, the changes in the gut microbes can be reversed by dieting and related weight loss. The qualitative and quantitative changes in the intake of specific food components (fatty acids, carbohydrates, micronutrients, prebiotics, probiotics), have not only consequences on the gut microbiota composition, but may modulate the expression of genes in host tissues such as the liver, adipose tissue, intestine, muscle. This in turn may drive or lessen the development of fat mass and metabolic disturbances associated with the gut barrier function and the systemic immunity. The relevance of the prebiotic or probiotic approaches in the management of obesity in humans is supported by few intervention studies in humans up to now, but the experimental data obtained with those compounds help to elucidate novel potential molecular targets relating diet with gut microbes. The metagenomic and integrative metabolomic approaches could help elucidate which bacteria, among the trillions in human gut, or more specifically which activities/genes, could participate to the control of host energy metabolism, and could be relevant for future therapeutic developments.
Overweight and obesity have reached epidemic levels. In 2008, 1,5 billion adults were overweight and over 200 million men and nearly 300 million women were obese. Worldwide obesity has more than doubled since 1980. Overweight and obesity are defined as an excess of fat mass but is often assessed by the calculation of the body mass index (BMI), calculated by dividing the weight (in kg) by the size2 (in meter2). Subjects with a BMI greater than or equal to 25 or 30 kg/m2, are considered as overweight and obese, respectively. .
Obesity is associated with a cluster of metabolic disorders such as insulin resistance, type 2 diabetes, fatty liver disease, atherosclerosis, hypertension and stroke but also with cancer, asthma, sleep apnoea, osteoarthritis, neuro-degeneration, and gall-bladder disease . The factors included in the definition of the metabolic syndrome are dysglycemia, raised blood pressure, elevated triglyceride levels, low high-density lipoprotein cholesterol levels and obesity (particularly central adiposity). The presence of any three of these five risk factors constitutes a diagnosis of metabolic syndrome .
The purpose of this review is to present the underlying mechanisms by which nutrients and food components which target the gut microbiota may play a role in the management of obesity and metabolic syndrome. This paper will mostly focus on the data relating the effect of non digestible carbohydrates exhibiting prebiotic properties, such as dietary fructans.
Gut microbiota composition and metabolism associated with the metabolic disorders in obese individuals
The gut microbiota present particular genetic and metabolic attributes, thereby giving the host the potential to live in symbiosis with those “external” cells which are ten fold more numerous than the number of cells in the human body [8, 11–13].
Novel culture-independent technologies based on the analysis of the bacterial 16S rRNA gene (e.g., pyrosequensing) allowed significant progress in the knowledge of our microbial partners with which we live in symbiosis [14, 15]. Most of the studies concerning the relation between host phenotype involving obesity and/or diabetes and gut microbiota, report changes of the relative abundance of phyla, gender, or species of bacteria, which correlate – positively or negatively- with biomarkers of the disease measured in the host (body mass index, glycemia, pro-inflammatory cytokines….) [10, 16]. The first study describing qualitative changes of the gut microbiota in human obese individuals was published a few years ago . In this study, the analysis of fecal samples of obese versus matched lean individuals showed a shift in bacterial phyla (lower Bacteroidetes and more Firmicutes) . Interestingly, the authors observed that after weight loss (following a fat restricted or a carbohydrate restricted low calorie diet), the ratio of Bacteroidetes to Firmicutes approached a lean type profile after 52 weeks . The focus on Bacteroidetes seems to be controversial. A reduction of Bacteroidetes community in obese patients was confirmed later . In another study, no differences were detected between obese and non-obese individuals in term of the proportion of Bacteroidetes measured in the fecal samples, and no significant changes of the percentage of Bacteroidetes occurred in feces from obese subjects upon weight loss . In accordance with these data, even more Bacteroidetes were detected in a group of obese subjects than in normal-weight individuals . A subgroup of Bacteroidetes (Prevotellaceae) was significantly enriched in the obese individuals. Moreover, the same authors showed that surgical treatment for morbid obesity (gastric bypass) strongly increased Gammaproteobacteria (members of the family Enterobacteriaceae) and proportionally decreased Firmicutes . The methodology used for bacterial analysis could explain certain discrepancies between results published by different groups .
Recently, three robust clusters referred to as “enterotypes” have been identified in individuals from different countries and a continent . They found that these enterotypes were identified by the variation at the level of one of the three following genera : Bacteroides, Prevotella and Ruminococcus. It is important to note that these enterotypes were not correlated with the host characteristics such as body mass index (BMI), age, gender or nationality. Importantly, this large study did not revealed any correlation between BMI and Firmicutes/Bacteroidetes ratio . However, although no difference in the microbiota composition has been described, a set of 3 genes modules have been strongly correlated with the host’s BMI, two of which are ATPase complexes, supporting the link found between the gut microbiota’s capacity for energy harvest and obesity in the host .
The hypothesis of more specific modulation of the gut microbiota community in obesity (instead of those obtained at the wide phylum levels) is supported by several studies. Bifidobacterium spp. number was higher in children who exhibited a normal weight at 7 years than in children developing overweight . More importantly they observed that the Staphylococcus aureus levels were lower in children who maintain a normal weight than in children becoming overweight several years later. The authors proposed that S. aureus may act as a trigger of low-grade inflammation , contributing to the development of obesity . In agreement with these last findings, significant differences have been observed in gut microbiota composition according to the body weight gain during pregnancy . Interestingly, the authors found significantly higher numbers of Bacteroides group in women with excessive weight gain upon pregnancy. They also established a positive correlation between the number of Bacteroides, Clostridium and Staphylococcus on the one hand, and the weight and BMI before pregnancy, on the other hand. The Bifidobacterium genus was present in higher numbers in normal-weight than in overweight women and also in women with lower weight gain during pregnancy . The Bifidobacterium genus was also poorly represented in the fecal samples of diabetic patients compared with healthy individuals . Nevertheless, a recent report has shown that weight loss could also be associated with reduced level of Bifidobacterium bifidum and Bifidobacterium breve counts and increased Bifidobacterium catenulatum. The level of Bifidobacterium genus is also decreased upon weight loss after bariatric surgery performed in obese individuals . Indeed, Bifidobacterium spp. represent an important and complex group of bacteria whose presence is often associated with beneficial health effects [30–32]. Another interesting bacterial species is Faecalibacterium prausnitzii, whose level is decreased in subjects with diabetes versus non diabetic obese, and which is associated negatively with inflammatory markers measured in the serum of obese individuals before and after roux- and Y gastric bypass surgery .
Other selective changes of bacterial composition have been described in obese human individuals, for which the relation with fat mass are sometimes controversial. Lactobacilli counts were higher in 8 out of 20 obese patients compared to the number measured in lean individuals (detected in only 1 out of 20) . Paradoxically, the weight loss due to calorie restriction and physical activity in overweight adolescents also increases lactobacilli . The focus on lactobacilli level may come from the fact that they are part of the Firmicutes phyla, which is increased upon obesity in most of the published studies. It seems, however, that the targeted probiotic approach with specific strains of Lactobacillus does not increase, but even decreases the metabolic alterations occurring in obesity, even if the number of interventional studies in humans, reported until now, remains low. The administration of Lactobacillus gasseri has been shown to decrease fat mass (visceral and subcutaneous) and body mass index in obese and type 2 diabetic patients . The administration of Lactobacillus spp. has been shown to positively impact on insulin sensitivity . They showed, in a double blind randomised study performed in 45 male subjects with type 2 diabetes, impaired, or normal glucose tolerance, that the administration of L. acidophilus NCFM for four weeks, preserved the insulin sensitivity -assessed by an euglycemic hyperinsulinemic clamp-, whereas it decreased in the placebo group . Finally, the early gut microbiota modulation with probiotics (Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12) reduced the body mass index in young children by restraining excessive weight gain during the first years of life (from 0 to 10 years of follow-up) . The probiotic approach in experimental studies in animals also suggests a decrease in adiposity in different animal models of obesity. For example, the treatment of high fat fed mice with specific strains of Lactobacillus plantarum or Lactobacillus paracasei spp paracasei reduced adipocyte cell size and body fat [36, 37]. More recently, it was shown that rats fed with high-energy-dense diet at pregnancy, throughout lactation and until 6 months of age, exhibited a lower weight gain, and a lower retroperitoneal adipose tissue when supplemented with Lactobacillus plantarum, an effect not observed when treated with Escherichia coli.
Those data suggest that specific changes in the gut microbiota characterize the obese state and associated metabolic diseases, including diabetes. However, we may not conclude, from the papers published until now, that targeting one specific bacterial target is sufficient to get an improvement of a complex disease such as obesity. Only few intervention studies have been performed with selected probiotics, and this had never been performed in order to counteract a drop in a specific “indigenous” bacteria considered as beneficial.
Gut microbes/nutrients interactions: a way to produce bioactive metabolites prone to interact with host tissues
It is becoming feasible and relevant to focus on the metabolic and functional properties of the gut microbiota. This approach reveals, in certain studies, that the changes in the gut microbiota composition occurring in obese mice (ob/ob mice or high fat diet fed mice) could be in favour of bacteria exhibiting saccharolytic activities [39–41]. The studies performed in germ free mice colonized with the caecal content obtained from obese and insulin-resistant mice have shown that the phenotype (obesity, insulin resistance and/or inflammation) can be transferred to the germ-free recipient through the microbial colonization, thereby suggesting that some elements of the gut microbes drive metabolic alterations in host tissues [40, 42]. The experiments performed on germ free mice colonized with gut microbes, and then exposed to different types of diets, are illustrating the fact that the host response in term of fat mass development depends on the interactions between gut microbes and nutrients (for review, see ). Recently, it has been shown in obese and lean human individuals that the increase in calorie intake (from 2400 to 3400 kcal/d) promoted rapid changes in the gut microbiota (20% increase in Firmicutes and a corresponding decrease in Bacteroidetes). This was associated with an increased energy harvest of ≈150 kcal, the overfeeding in lean individuals being accompanied by a greater fractional decrease in stool energy loss .
The promoting effect of the gut microbiota on intestinal glucose absorption has been suggested in germ free mice colonized with the saccharolytic Bacteroides thetaiotaomicron : this effect supports the fact that events occurring upon bacterial fermentation may have an effect in the upper part of the gut, and thereby affecting digestible carbohydrates availability . Conventionalization of germ free mice has been demonstrated to promote body weight gain and fat mass development . Interestingly, the conventionalization also brought about a general increase in the activity of the enzyme lipoprotein lipase (LPL), catalyzing the release of fatty acids and triacylglycerol from circulating lipoproteins in muscle, and adipose tissue. The authors proposed that such an increase was the consequence of suppression of the Fasting-Induced Adipose Factor (FIAF) in the gut. Given that FIAF inhibits the LPL activity, the blunted FIAF expression in conventionalized germ free mice could thus participate to the accumulation of lipids in the adipose tissue . In another set of experiment the authors maintained germ free mice or conventionalized mice on a high fat/high carbohydrates diet (western diet). They found that germ free mice were resistant to the high-fat diet-induced body weight and fat mass gain than the conventionalized mice . This increase in fat mass upon high fat diet feeding in conventionalized versus germ free animals, supports the fact that the fat storage is favoured by the presence of the gut microbiota [46, 47]. However, the observation of the metabolic response to high fat diet of germ free versus conventionalized mice, suggest that the presence of carbohydrates in the diet may modulate the development of obesity upon colonization of the gut .
Just as the gut microbes influence the metabolic feature of nutrients, it is also clear that the ingestion of specific nutrients play a role in the microbial changes. We have previously demonstrated that diet-induced obesity (high fat-low carbohydrates diet) in mice markedly affects the gut microbial community whereby the levels of Bifidibacterium spp. and E. rectale/Cl. coccoides group were significantly reduced [25, 49]. The effect of feeding a high fat diet to conventional mice and RELMb knock-out mice, the latter of which are resistant to fat-induced obesity, resulted in a decrease in Bacteroidetes and an increase in Firmicutes and Proteobacteria for both genotypes, indicating that high fat diet itself rather than the obese state may account for the changes in microbiota composition .
Other microbial derived elements play a role in the regulation of host homeostasis. Nutrients which escape the digestion to the upper part of the gut, are fermented by gut microbes, which release namely short chain fatty acids (SCFA) (acetate, propionate, butyrate). Those bacterial metabolites are absorbed by host intestinal tissue, and thereby could participate to “energy harvest”. In addition, SCFA are able to act as signalling molecules in host tissues, by linking selected G protein-coupled receptors, free fatty acid receptors FFAR2 and FFAR3 . In fact, FFAR3-/- mice, which do not express the receptor able to bind the SCFA, gain less weight when colonized with saccharolytic bacteria (B. thetaiotaomicron and M. smithii), as compared to mice expressing the receptor . This suggests that the SCFA may promote weight gain by binding to this receptor. Other data have shown that SFCA (acetate, propionate) may stimulate adipogenesis in the white adipose tissue via FFAR2 activation .
These data suggest that the ingestion of fermentable carbohydrates de facto contribute to an increase in fat mass. Nevertheless, numerous other data obtained with non digestible/highly fermentable carbohydrates with prebiotic properties, counteract this hypothesis.
Interaction of prebiotic carbohydrates with host energy metabolism
The question of the relevance of specific gut microbial species/phyla in the improvement of metabolic syndrome by fructans-type prebiotics is a matter of debate. As previously described, several reports have shown that obesity induced following dietary manipulations (high fat feeding) or genetic deletion (leptin deficient models) is characterized by changes in gut microbiota towards a decreased number of bifidobacteria [70–75]. This group of bacteria has been shown to reduce intestinal LPS levels in mice and to improve the mucosal barrier function [25, 40, 49, 76]. We can not preclude, in view of the complexity of the gut microbiota, that bifidobacteria are the sole actors in the improvement of metabolic disorders associated with obesity by prebiotics. Other non digestible/fermentable carbohydrates such as resistant starch (type 4), are able to increase Actinobacteria and specific types of bifidobacteria (Bifidobacterium adolescentis) in human individuals . Those resistant starches have also been proposed as nutrients able to control glycemia and food intake by changing the profile of gut hormones, such as GLP-1. However, there is no proof until now that the increase in Bifidobacteria participates per se to the increase in the endocrine function of the gut upon prebiotics treatment.
In fact, we have recently studied the composition of the gut microbiota using the pyrosequencing of the 16S rRNA gene of the caecal content of ob/ob mice treated with prebiotics, and we discovered more than a hundred sequence which were different upon prebiotic treatment, some of them being modified by more than ten fold, some of them being correlated with the number of L cells in the colon and the intestine (PD. Cani, personal communication).
Altogether, those data imply that, if the gut microbial activity is devoted to ferment carbohydrates, the energy sparing due to the production of the short chain fatty acids may be supplanted by other biochemical events occurring in the gut upon the changes in the microbial composition and/or activity. In fact, we have recently shown upon fructans supplementation in high fat diet fed mice, that the increase in fermentation occurring in the caecum, leads to a decrease in the expression of the genes responding to the short chain fatty acids (FFAR2) in the adipose tissue , and thereby lessens the development of fat mass . Adaptive processes thus take place far from the gut (for example in the liver and the adipose tissue) upon prebiotic approach, which could contribute to an improvement of metabolic syndrome. Those effects are illustrated in figure 3.
Conclusion and perspectives
The elucidation of specific bacterial phyla/gender/species whose number correlates with fat mass development could help discovering a new type of “target” in the management of obesity and related disorders. Most of the data published until now in humans, have analyzed fecal samples in order to relate the changes in gut microbiota composition, obesity or food intake behaviour. In fact, the composition of the fecal microbiota does not fully represent the microbial composition in the colon. Moreover, recent data suggest that the mucosa of proximal small intestine is highly responsive to changes in the microbial composition driven by a probiotic approach . In addition, we have shown that the modulation of the endocrine L cells number, induced in mice by the prebiotic approach, is occurring not only in the colon, but also in the jejunum. Finally, the events linking the host microbes to diabetes would also implicate the oral microbiota, which can be modified by prebiotics an probiotics [80, 81]. All those data suggest that, even if the vast majority of microbes reside in the colon, one might also pay attention to microbial modulation occurring in other body compartments in order to understand how the interplay between nutrients and gut microbes influences host health, namely in the context of diabetes and obesity.
It is crucial to analyse the metabolic potential of the gut microbes in totally in order to understand the biochemical mechanism underlying the energy sparing or energy expenditure due to nutrients/microbial interaction. The saccharolytic activity of the gut microbiota, namely through the production of short chain fatty acids, has been proposed as a potential driver of adipogenesis. However, highly fermentable carbohydrates, such as prebiotics, are able to counteract most of the metabolic alterations linked to obesity, despite (or thanks to?) the fact that they are actively fermented into short chain fatty acids. It is likely that the targeted modification of the gut microbiota can also be obtained by the administration of bacteria themselves. For example, a targeted probiotic approach leading to the production of bioactive lipids prone to regulate host homeostasis (conjugated linoleic acids) are particularly interesting . Finally, we largely ignore if and how the host itself may influence the composition of the gut microbiota, and thereby take advantage of its symbiotic partner. We have recently shown in mice deprived of dietary magnesium for 2 days that the magnesium deficiency promoted systemic and intestinal inflammation just within the two days . However, those detrimental effects were abolished after three weeks of magnesium-deficiency, a phenomenon associated with specific changes in gut microbiota composition in favour of bacteria reinforcing the gut barrier function (increased bifidobacteria) . Therefore, it’s possible that not only macronutrients, but also micronutrients and phytochemicals present in minor concentrations in the diet are interacting with the gut microbes to modulate host physiology. The relevance of this in the field of obesity and associated metabolic disorders remains to be unravelled.
The gut microbiota thus appears as an important target to consider in the management of obesity and related diseases. The advantage of this target is that both nutritional and pharmacological approaches will be developed upon the increasing knowledge of host-microbe interactions. The metabolomic approach will be without any doubt, a way to understand how microbial activities are related to host phenotype metabolism. The metabolomic NMR analysis of different tissues and fluids of conventional versus germ free mice allowed the presence of a specific family of bacteria (Coriobacteriaceae family) to be linked with the regulation of hepatic intermediary and xenobiotic metabolism . Recently, it was shown by NMR analysis of biomarkers in the serum of genetically obese versus lean growing pigs that changes in gut microbiota-related metabolites occurred, including trimethylamine-N-oxide and choline, in addition to markers of lipogenesis, lipid oxidation, energy utilization and partition, protein and amino acid metabolism . Future research needs to be performed to assess the relevance of those metabolites in host physiology homeostasis, a key question being: are there only markers or actors of the interactions between diet, host, and gut microbes?
Key words : gut microbiota, obesity, prebiotics, inflammation, gut peptides.
PDC is research associate from the FRS-FNRS (Fonds de la Recherche Scientifique, Belgique). NMD and PDC are recipients of subsides from the Fonds National de la Recherche Scientifique (FNRS/FRSM) and from the « fonds spéciaux de recherche », UCL (Université catholique de Louvain).
This article has been published as part of Microbial Cell Factories Volume 10 Supplement 1, 2011: Proceedings of the 10th Symposium on Lactic Acid Bacterium. The full contents of the supplement are available online at http://www.microbialcellfactories.com/supplements/10/S1.
- World health organization - Obesity and overweight - Fact sheet N°311 - Updated March 2011. [http://www.who.int/mediacentre/factsheets/fs311/en/index.html]
- Hotamisligil GS: Inflammation and metabolic disorders. Nature. 2006, 444: 860-867. 10.1038/nature05485.View Article
- Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC: Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009, 120: 1640-1645. 10.1161/CIRCULATIONAHA.109.192644.View Article
- Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, Mende DR, Li J, Xu J, Li S, Li D, Cao J, Wang B, Liang H, Zheng H, Xie Y, Tap J, Lepage P, Bertalan M, Batto JM, Hansen T, Le PD, Linneberg A, Nielsen HB, Pelletier E, Renault P, Sicheritz-Ponten T, Turner K, Zhu H, Yu C, Li S, Jian M, Zhou Y, Li Y, Zhang X, Li S, Qin N, Yang H, Wang J, Brunak S, Dore J, Guarner F, Kristiansen K, Pedersen O, Parkhill J, Weissenbach J, Bork P, Ehrlich SD, Wang J: A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010, 464: 59-65. 10.1038/nature08821.View Article
- Diamant M, Blaak EE, de Vos WM: Do nutrient-gut-microbiota interactions play a role in human obesity, insulin resistance and type 2 diabetes?. Obes Rev. 2010
- Turnbaugh PJ, Ridaura VK, Faith JJ, Rey FE, Knight R, Gordon JI: The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci Transl Med. 2009, 1: 6ra 14-View Article
- Caesar R, Fak F, Backhed F: Effects of gut microbiota on obesity and atherosclerosis via modulation of inflammation and lipid metabolism. J Intern Med. 2010, 268: 320-328. 10.1111/j.1365-2796.2010.02270.x.View Article
- Cani PD, Delzenne NM: The gut microbiome as therapeutic target. Pharmacol Ther. 2011, 130: 202-212. 10.1016/j.pharmthera.2011.01.012.View Article
- Delzenne NM, Cani PD: Nutritional modulation of gut microbiota in the context of obesity and insulin resistance: Potential interest of prebiotics. International Dairy Journal. 2010, 20: 277-280. 10.1016/j.idairyj.2009.11.006.View Article
- Ley RE: Obesity and the human microbiome. Curr Opin Gastroenterol. 2010, 26: 5-11. 10.1097/MOG.0b013e328333d751.View Article
- Jia W, Li H, Zhao L, Nicholson JK: Gut microbiota: a potential new territory for drug targeting. Nat Rev Drug Discov. 2008, 7: 123-129. 10.1038/nrd2505.View Article
- Round JL, Mazmanian SK: The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol. 2009, 9: 313-323. 10.1038/nri2515.View Article
- Neish AS: Microbes in gastrointestinal health and disease. Gastroenterology. 2009, 136: 65-80. 10.1053/j.gastro.2008.10.080.View Article
- Hsiao WW, Fraser-Liggett CM: Human Microbiome Project--paving the way to a better understanding of ourselves and our microbes. Drug Discov Today. 2009, 14: 331-333. 10.1016/j.drudis.2009.03.001.View Article
- Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI: The human microbiome project. Nature. 2007, 449: 804-810. 10.1038/nature06244.View Article
- Ley RE, Backhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI: Obesity alters gut microbial ecology. Proc Natl Acad Sci U S A. 2005, 102: 11070-11075. 10.1073/pnas.0504978102.View Article
- Ley RE, Turnbaugh PJ, Klein S, Gordon JI: Microbial ecology: human gut microbes associated with obesity. Nature. 2006, 444: 1022-1023. 10.1038/4441022a.View Article
- Armougom F, Henry M, Vialettes B, Raccah D, Raoult D: Monitoring bacterial community of human gut microbiota reveals an increase in Lactobacillus in obese patients and Methanogens in anorexic patients. PLoS One. 2009, 4: e7125-10.1371/journal.pone.0007125.View Article
- Duncan SH, Lobley GE, Holtrop G, Ince J, Johnstone AM, Louis P, Flint HJ: Human colonic microbiota associated with diet, obesity and weight loss. Int J Obes (Lond). 2008, 32: 1720-1724. 10.1038/ijo.2008.155.View Article
- Zhang H, DiBaise JK, Zuccolo A, Kudrna D, Braidotti M, Yu Y, Parameswaran P, Crowell MD, Wing R, Rittmann BE, Krajmalnik-Brown R: Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci U S A. 2009, 106: 2365-2370. 10.1073/pnas.0812600106.View Article
- Hoyles L, McCartney AL: What do we mean when we refer to Bacteroidetes populations in the human gastrointestinal microbiota?. FEMS Microbiol Lett. 2009, 299: 175-183. 10.1111/j.1574-6968.2009.01741.x.View Article
- Arumugam M, Raes J, Pelletier E, Le PD, Yamada T, Mende DR, Fernandes GR, Tap J, Bruls T, Batto JM, Bertalan M, Borruel N, Casellas F, Fernandez L, Gautier L, Hansen T, Hattori M, Hayashi T, Kleerebezem M, Kurokawa K, Leclerc M, Levenez F, Manichanh C, Nielsen HB, Nielsen T, Pons N, Poulain J, Qin J, Sicheritz-Ponten T, Tims S, Torrents D, Ugarte E, Zoetendal EG, Wang J, Guarner F, Pedersen O, de Vos WM, Brunak S, Dore J, Consortium M, Weissenbach J, Ehrlich SD, Bork P, Antolin M, Artiguenave F, Blottiere HM, Almeida M, Brechot C, Cara C, Chervaux C, Cultrone A, Delorme C, Denariaz G, Dervyn R, Foerstner KU, Friss C, van de GM, Guedon E, Haimet F, Huber W, van Hylckama-Vlieg J, Jamet A, Juste C, Kaci G, Knol J, Lakhdari O, Layec S, Le RK, Maguin E, Merieux A, Melo MR, M'rini C, Muller J, Oozeer R, Parkhill J, Renault P, Rescigno M, Sanchez N, Sunagawa S, Torrejon A, Turner K, Vandemeulebrouck G, Varela E, Winogradsky Y, Zeller G: Enterotypes of the human gut microbiome. Nature. 2011.
- Kalliomaki M, Collado MC, Salminen S, Isolauri E: Early differences in fecal microbiota composition in children may predict overweight. Am J Clin Nutr. 2008, 87: 534-538.
- Lundell AC, Adlerberth I, Lindberg E, Karlsson H, Ekberg S, Aberg N, Saalman R, Hock B, Steinkasserer A, Hesselmar B, Wold AE, Rudin A: Increased levels of circulating soluble CD14 but not CD83 in infants are associated with early intestinal colonization with Staphylococcus aureus. Clin Exp Allergy. 2007, 37: 62-71. 10.1111/j.1365-2222.2006.02625.x.View Article
- Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C, Waget A, Delmee E, Cousin B, Sulpice T, Chamontin B, Ferrieres J, Tanti JF, Gibson GR, Casteilla L, Delzenne NM, Alessi MC, Burcelin R: Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007, 56: 1761-1772. 10.2337/db06-1491.View Article
- Collado MC, Isolauri E, Laitinen K, Salminen S: Distinct composition of gut microbiota during pregnancy in overweight and normal-weight women. Am J Clin Nutr. 2008, 88: 894-899.
- Wu X, Ma C, Han L, Nawaz M, Gao F, Zhang X, Yu P, Zhao C, Li L, Zhou A, Wang J, Moore JE, Millar BC, Xu J: Molecular characterisation of the faecal microbiota in patients with type II diabetes. Curr Microbiol. 2010, 61: 69-78. 10.1007/s00284-010-9582-9.View Article
- Santacruz A, Marcos A, Warnberg J, Marti A, Martin-Matillas M, Campoy C, Moreno LA, Veiga O, Redondo-Figuero C, Garagorri JM, Azcona C, Delgado M, Garcia-Fuentes M, Collado MC, Sanz Y: Interplay between weight loss and gut microbiota composition in overweight adolescents. Obesity (Silver Spring). 2009, 17: 1906-1915. 10.1038/oby.2009.112.View Article
- Furet JP, Kong LC, Tap J, Poitou C, Basdevant A, Bouillot JL, Mariat D, Corthier G, Dore J, Henegar C, Rizkalla S, Clement K: Differential adaptation of human gut microbiota to bariatric surgery-induced weight loss: links with metabolic and low-grade inflammation markers. Diabetes. 2010, 59: 3049-3057. 10.2337/db10-0253.View Article
- Boesten RJ, de Vos WM: Interactomics in the human intestine: Lactobacilli and Bifidobacteria make a difference. J Clin Gastroenterol. 2008, 42: S163-S167.View Article
- Boesten RJ, Schuren FH, de Vos WM: A Bifidobacterium mixed-species microarray for high resolution discrimination between intestinal bifidobacteria. J Microbiol Methods. 2009, 76: 269-277. 10.1016/j.mimet.2008.12.006.View Article
- Turroni F, Marchesi JR, Foroni E, Gueimonde M, Shanahan F, Margolles A, van SD, Ventura M: Microbiomic analysis of the bifidobacterial population in the human distal gut. ISME J. 2009, 3: 745-751. 10.1038/ismej.2009.19.View Article
- Kadooka Y, Sato M, Imaizumi K, Ogawa A, Ikuyama K, Akai Y, Okano M, Kagoshima M, Tsuchida T: Regulation of abdominal adiposity by probiotics (Lactobacillus gasseri SBT2055) in adults with obese tendencies in a randomized controlled trial. Eur J Clin Nutr. 2010, 64: 636-643. 10.1038/ejcn.2010.19.View Article
- Andreasen AS, Larsen N, Pedersen-Skovsgaard T, Berg RM, Moller K, Svendsen KD, Jakobsen M, Pedersen BK: Effects of Lactobacillus acidophilus NCFM on insulin sensitivity and the systemic inflammatory response in human subjects. Br J Nutr. 2010, 104: 1831-1838. 10.1017/S0007114510002874.View Article
- Luoto R, Laitinen K, Nermes M, Isolauri E: Impact of maternal probiotic-supplemented dietary counselling on pregnancy outcome and prenatal and postnatal growth: a double-blind, placebo-controlled study. Br J Nutr. 2010, 103: 1792-1799. 10.1017/S0007114509993898.View Article
- Takemura N, Okubo T, Sonoyama K: Lactobacillus plantarum strain No. 14 reduces adipocyte size in mice fed high-fat diet. Exp Biol Med (Maywood ). 2010, 235: 849-856. 10.1258/ebm.2010.009377.View Article
- Aronsson L, Huang Y, Parini P, Korach-Andre M, Hakansson J, Gustafsson JA, Pettersson S, Arulampalam V, Rafter J: Decreased fat storage by Lactobacillus paracasei is associated with increased levels of angiopoietin-like 4 protein (ANGPTL4). PLoS One. 2010, 5: pii-e13087.View Article
- Karlsson CL, Molin G, Fak F, Johansson Hagslatt ML, Jakesevic M, Hakansson A, Jeppsson B, Westrom B, Ahrne S: Effects on weight gain and gut microbiota in rats given bacterial supplements and a high-energy-dense diet from fetal life through to 6 months of age. Br J Nutr. 2011, 1-9.
- Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI: An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006, 444: 1027-1031. 10.1038/nature05414.View Article
- Turnbaugh PJ, Backhed F, Fulton L, Gordon JI: Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe. 2008, 3: 213-223. 10.1016/j.chom.2008.02.015.View Article
- Tilg H, Moschen AR, Kaser A: Obesity and the microbiota. Gastroenterology. 2009, 136: 1476-1483. 10.1053/j.gastro.2009.03.030.View Article
- Vijay-Kumar M, Aitken JD, Carvalho FA, Cullender TC, Mwangi S, Srinivasan S, Sitaraman SV, Knight R, Ley RE, Gewirtz AT: Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science. 2010, 328: 228-231. 10.1126/science.1179721.View Article
- Backhed F, Crawford PA: Coordinated regulation of the metabolome and lipidome at the host-microbial interface. Biochim Biophys Acta. 2010, 1801: 240-245.View Article
- Jumpertz R, Le DS, Turnbaugh PJ, Trinidad C, Bogardus C, Gordon JI, Krakoff J: Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans. Am J Clin Nutr. 2011.
- Hooper LV, Wong MH, Thelin A, Hansson L, Falk PG, Gordon JI: Molecular analysis of commensal host-microbial relationships in the intestine. Science. 2001, 291: 881-884. 10.1126/science.291.5505.881.View Article
- Backhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, Semenkovich CF, Gordon JI: The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A. 2004, 101: 15718-15723. 10.1073/pnas.0407076101.View Article
- Backhed F, Manchester JK, Semenkovich CF, Gordon JI: Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci U S A. 2007, 104: 979-984. 10.1073/pnas.0605374104.View Article
- Fleissner CK, Huebel N, bd El-Bary MM, Loh G, Klaus S, Blaut M: Absence of intestinal microbiota does not protect mice from diet-induced obesity. Br J Nutr. 2010, 104: 919-929. 10.1017/S0007114510001303.View Article
- Cani PD, Neyrinck AM, Fava F, Knauf C, Burcelin RG, Tuohy KM, Gibson GR, Delzenne NM: Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia. 2007, 50: 2374-2383. 10.1007/s00125-007-0791-0.View Article
- Hildebrandt MA, Hoffmann C, Sherrill-Mix SA, Keilbaugh SA, Hamady M, Chen YY, Knight R, Ahima RS, Bushman F, Wu GD: High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology. 2009, 137: 1716-1724. 10.1053/j.gastro.2009.08.042.View Article
- de LG, de La Serre CB, Raybould HE: Vagal afferent neurons in high fat diet-induced obesity; intestinal microflora, gut inflammation and cholecystokinin. Physiol Behav. 2011
- Ding S, Chi MM, Scull BP, Rigby R, Schwerbrock NM, Magness S, Jobin C, Lund PK: High-fat diet: bacteria interactions promote intestinal inflammation which precedes and correlates with obesity and insulin resistance in mouse. PLoS One. 2010, 5: e12191-10.1371/journal.pone.0012191.View Article
- Le PE, Loison C, Struyf S, Springael JY, Lannoy V, Decobecq ME, Brezillon S, Dupriez V, Vassart G, Van DJ, Parmentier M, Detheux M: Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J Biol Chem. 2003, 278: 25481-25489. 10.1074/jbc.M301403200.View Article
- Samuel BS, Shaito A, Motoike T, Rey FE, Backhed F, Manchester JK, Hammer RE, Williams SC, Crowley J, Yanagisawa M, Gordon JI: Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc Natl Acad Sci U S A. 2008, 105: 16767-16772. 10.1073/pnas.0808567105.View Article
- Hong YH, Nishimura Y, Hishikawa D, Tsuzuki H, Miyahara H, Gotoh C, Choi KC, Feng DD, Chen C, Lee HG, Katoh K, Roh SG, Sasaki S: Acetate and propionate short chain fatty acids stimulate adipogenesis via GPCR43. Endocrinology. 2005, 146: 5092-5099. 10.1210/en.2005-0545.View Article
- Cani PD, Delzenne NM: The role of the gut microbiota in energy metabolism and metabolic disease. Curr Pharm Des. 2009, 15: 1546-1558. 10.2174/138161209788168164.View Article
- Neyrinck AM, Delzenne NM: Potential interest of gut microbial changes induced by non-digestible carbohydrates of wheat in the management of obesity and related disorders. Curr Opin Clin Nutr Metab Care. 2010, 13: 722-728. 10.1097/MCO.0b013e32833ec3fb.View Article
- Roberfroid M, Gibson GR, Hoyles L, McCartney AL, Rastall R, Rowland I, Wolvers D, Watzl B, Szajewska H, Stahl B, Guarner F, Respondek F, Whelan K, Coxam V, Davicco MJ, Leotoing L, Wittrant Y, Delzenne NM, Cani PD, Neyrinck AM, Meheust A: Prebiotic effects: metabolic and health benefits. Br J Nutr. 2010, 104 (Suppl 2): S1-63.View Article
- Abrams SA, Griffin IJ, Hawthorne KM, Ellis KJ: Effect of prebiotic supplementation and calcium intake on body mass index. J Pediatr. 2007, 151: 293-298. 10.1016/j.jpeds.2007.03.043.View Article
- Genta S, Cabrera W, Habib N, Pons J, Carillo IM, Grau A, Sanchez S: Yacon syrup: beneficial effects on obesity and insulin resistance in humans. Clin Nutr. 2009, 28: 182-187. 10.1016/j.clnu.2009.01.013.View Article
- Parnell JA, Reimer RA: Weight loss during oligofructose supplementation is associated with decreased ghrelin and increased peptide YY in overweight and obese adults1. Am J Clin Nutr. 2009, 89: 1751-1759. 10.3945/ajcn.2009.27465.View Article
- Cani PD, Lecourt E, Dewulf EM, Sohet FM, Pachikian BD, Naslain D, De BF, Neyrinck AM, Delzenne NM: Gut microbiota fermentation of prebiotics increases satietogenic and incretin gut peptide production with consequences for appetite sensation and glucose response after a meal. Am J Clin Nutr. 2009, 90: 1236-1243. 10.3945/ajcn.2009.28095.View Article
- Cani PD, Delzenne NM: Interplay between obesity and associated metabolic disorders: new insights into the gut microbiota. Curr Opin Pharmacol. 2009, 9: 737-743. 10.1016/j.coph.2009.06.016.View Article
- Delzenne NM, Cani PD, Neyrinck AM: Modulation of glucagon-like peptide 1 and energy metabolism by inulin and oligofructose: experimental data. J Nutr. 2007, 137: 2547S-2551S.
- Cani PD, Delzenne NM: Gut microflora as a target for energy and metabolic homeostasis. Curr Opin Clin Nutr Metab Care. 2007, 10: 729-734. 10.1097/MCO.0b013e3282efdebb.View Article
- Cani PD, Knauf C, Iglesias MA, Drucker DJ, Delzenne NM, Burcelin R: Improvement of glucose tolerance and hepatic insulin sensitivity by oligofructose requires a functional glucagon-like Peptide 1 receptor. Diabetes. 2006, 55: 1484-1490. 10.2337/db05-1360.View Article
- Cani PD, Possemiers S, Van de WT, Guiot Y, Everard A, Rottier O, Geurts L, Naslain D, Neyrinck A, Lambert DM, Muccioli GG, Delzenne NM: Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut. 2009, 58: 1091-1103. 10.1136/gut.2008.165886.View Article
- Muccioli GG, Naslain D, Backhed F, Reigstad CS, Lambert DM, Delzenne NM, Cani PD: The endocannabinoid system links gut microbiota to adipogenesis. Mol Syst Biol. 2010, 6: 392-View Article
- Reigstad CS, Lunden GO, Felin J, Backhed F: Regulation of serum amyloid A3 (SAA3) in mouse colonic epithelium and adipose tissue by the intestinal microbiota. PLoS One. 2009, 4: e5842-10.1371/journal.pone.0005842.View Article
- Waldram A, Holmes E, Wang Y, Rantalainen M, Wilson ID, Tuohy KM, McCartney AL, Gibson GR, Nicholson JK: Top-down systems biology modeling of host metabotype-microbiome associations in obese rodents. J Proteome Res. 2009, 8: 2361-2375. 10.1021/pr8009885.View Article
- Wang Z, Xiao G, Yao Y, Guo S, Lu K, Sheng Z: The role of bifidobacteria in gut barrier function after thermal injury in rats. J Trauma. 2006, 61: 650-657. 10.1097/01.ta.0000196574.70614.27.View Article
- Griffiths EA, Duffy LC, Schanbacher FL, Qiao H, Dryja D, Leavens A, Rossman J, Rich G, Dirienzo D, Ogra PL: In vivo effects of bifidobacteria and lactoferrin on gut endotoxin concentration and mucosal immunity in Balb/c mice. Dig Dis Sci. 2004, 49: 579-589.View Article
- Wang ZT, Yao YM, Xiao GX, Sheng ZY: Risk factors of development of gut-derived bacterial translocation in thermally injured rats. World J Gastroenterol. 2004, 10: 1619-1624.View Article
- Commane DM, Shortt CT, Silvi S, Cresci A, Hughes RM, Rowland IR: Effects of fermentation products of pro- and prebiotics on trans-epithelial electrical resistance in an in vitro model of the colon. Nutr Cancer. 2005, 51: 102-109. 10.1207/s15327914nc5101_14.View Article
- Ruan X, Shi H, Xia G, Xiao Y, Dong J, Ming F, Wang S: Encapsulated Bifidobacteria reduced bacterial translocation in rats following hemorrhagic shock and resuscitation. Nutrition. 2007, 23: 754-761. 10.1016/j.nut.2007.07.002.View Article
- Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, Burcelin R: Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes. 2008, 57: 1470-1481. 10.2337/db07-1403.View Article
- Martinez I, Kim J, Duffy PR, Schlegel VL, Walter J: Resistant starches types 2 and 4 have differential effects on the composition of the fecal microbiota in human subjects. PLoS One. 2010, 5: e15046-10.1371/journal.pone.0015046.View Article
- Dewulf EM, Cani PD, Neyrinck AM, Possemiers S, Holle AV, Muccioli GG, Deldicque L, Bindels LB, Pachikian BD, Sohet FM, Mignolet E, Francaux M, Larondelle Y, Delzenne NM: Inulin-type fructans with prebiotic properties counteract GPR43 overexpression and PPARgamma-related adipogenesis in the white adipose tissue of high-fat diet-fed mice. J Nutr Biochem. 2011, 22: 712-722. 10.1016/j.jnutbio.2010.05.009.View Article
- van BP, Troost F, van der MC, Hooiveld G, Boekschoten M, Brummer RJ, Kleerebezem M: Human mucosal in vivo transcriptome responses to three lactobacilli indicate how probiotics may modulate human cellular pathways. Proc Natl Acad Sci U S A. 2011, 108 (Suppl 1): 4562-4569.
- Devine DA, Marsh PD: Prospects for the development of probiotics and prebiotics for oral applications. J Oral Microbiol. 2009, 1: 1-doi:10.3402/jom.v1i0.1949View Article
- Ohlrich EJ, Cullinan MP, Leichter JW: Diabetes, periodontitis, and the subgingival microbiota. J Oral Microbiol. 2010, 2: doi:10.3402/jom.v2i0.5818
- Wall R, Ross RP, Shanahan F, O'Mahony L, O'Mahony C, Coakley M, Hart O, Lawlor P, Quigley EM, Kiely B, Fitzgerald GF, Stanton C: Metabolic activity of the enteric microbiota influences the fatty acid composition of murine and porcine liver and adipose tissues. Am J Clin Nutr. 2009, 89: 1393-1401. 10.3945/ajcn.2008.27023.View Article
- Pachikian BD, Neyrinck AM, Deldicque L, de Backer FC, Catry E, Dewulf EM, Sohet FM, Bindels LB, Everard A, Francaux M, Guiot Y, Cani PD, Delzenne NM: Changes in intestinal bifidobacteria levels are associated with the inflammatory response in magnesium-deficient mice. J Nutr. 2010, 140: 509-514. 10.3945/jn.109.117374.View Article
- Claus SP, Ellero SL, Berger B, Krause L, Bruttin A, Molina J, Paris A, Want EJ, de WI, Cloarec O, Richards SE, Wang Y, Dumas ME, Ross A, Rezzi S, Kochhar S, Van BP, Lindon JC, Holmes E, Nicholson JK: Colonization-induced host-gut microbial metabolic interaction. MBio. 2011, 2: pii-e00271-10.View Article
- He Q, Ren P, Kong X, Wu Y, Wu G, Li P, Hao F, Tang H, Blachier F, Yin Y: Comparison of serum metabolite compositions between obese and lean growing pigs using an NMR-based metabonomic approach. J Nutr Biochem. 2011.
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