Gut Microbiota Signatures Predict Host and Microbiota Responses to Dietary Interventions in Obese Individuals
Korpela, K. ; Flint, H.J. ; Johnstone, A.M. ; Lappi, J. ; Poutanen, K. ; Dewulf, E. ; Delzenne, N. ; Vos, W.M. de; Salonen, A. - \ 2014
PLoS ONE 9 (2014)3. - ISSN 1932-6203
dna-extraction methods - intestinal microbiota - metabolic syndrome - species response - resistant starch - healthy humans - double-blind - weight-loss - human colon - differentiate
Background Interactions between the diet and intestinal microbiota play a role in health and disease, including obesity and related metabolic complications. There is great interest to use dietary means to manipulate the microbiota to promote health. Currently, the impact of dietary change on the microbiota and the host metabolism is poorly predictable and highly individual. We propose that the responsiveness of the gut microbiota may depend on its composition, and associate with metabolic changes in the host. Methodology Our study involved three independent cohorts of obese adults (n = 78) from Belgium, Finland, and Britain, participating in different dietary interventions aiming to improve metabolic health. We used a phylogenetic microarray for comprehensive fecal microbiota analysis at baseline and after the intervention. Blood cholesterol, insulin and inflammation markers were analyzed as indicators of host response. The data were divided into four training set – test set pairs; each intervention acted both as a part of a training set and as an independent test set. We used linear models to predict the responsiveness of the microbiota and the host, and logistic regression to predict responder vs. non-responder status, or increase vs. decrease of the health parameters. Principal Findings Our models, based on the abundance of several, mainly Firmicute species at baseline, predicted the responsiveness of the microbiota (AUC = 0.77–1; predicted vs. observed correlation = 0.67–0.88). Many of the predictive taxa showed a non-linear relationship with the responsiveness. The microbiota response associated with the change in serum cholesterol levels with an AUC of 0.96, highlighting the involvement of the intestinal microbiota in metabolic health. Conclusion This proof-of-principle study introduces the first potential microbial biomarkers for dietary responsiveness in obese individuals with impaired metabolic health, and reveals the potential of microbiota signatures for personalized nutrition.
Anaerostipes rhamnosivorans sp. nov., a human intestinal butyrate forming bacterium
Bui, T.P.N. ; Vos, W.M. de; Plugge, C.M. - \ 2014
International Journal of Systematic and Evolutionary Microbiology 64 (2014)3. - ISSN 1466-5026 - p. 787 - 793.
renaturation rates - dna hybridization - human colon - human feces - microbiota - gene - gut
A novel butyrate producing bacterium, strain 1y-2T, was isolated from a stool sample of a 1-year old, healthy Dutch infant. The isolate was obtained by using lactate and acetate as sources of carbon and energy. The strain was Gram-variable, strictly anaerobic, spore-forming and formed curly rod-shaped cells that fermented glucose into butyrate, lactate, formate and acetate as main products. The G + C composition of the strain was 44.5 % and its major cellular fatty acids were C12:00, C19:1 iso I and C16:00. Strain 1y-2T was related to Anaerostipes caccae DSM14662T based on 16S rRNA analysis with 3 % divergence but hybridization studies of their genomic DNA revealed only 33 % similarity. Moreover, strain 1y-2T showed marked physiological and biochemical differences with known Anaerostipes species. Based on the phylogenetic, chemotypic and phenotypic criteria, we propose that strain 1y-2T should be classified in the genus Anaerostipes as a novel species, Anaerostipes rhamnosivorans sp. nov. The type strain is 1y-2T (= DSM 26241T = KCTC 15316T)
Evaluation of microbial community reproducibility, stability and composition in a human distal gut chemostat model
McDonald, J.A. ; Schroeter, K. ; Fuentes Enriquez de Salamanca, S. ; Heikamp-de Jong, G.A.M. ; Khursigara, C.M. ; Vos, W.M. de; Allen-Vercoe, E. - \ 2013
Journal of Microbiological Methods 95 (2013)2. - ISSN 0167-7012 - p. 167 - 174.
phylogenetic microarray analysis - gel-electrophoresis analysis - continuous-culture system - 16s ribosomal-rna - intestinal microbiota - human colon - bacterial-populations - mixed populations - retention time - fermentation
In vitro gut models provide several advantages over in vivo models for the study of the human gut microbiota. However, because communities developed in these models are inevitably simplified simulations of the in vivo environment, it is necessary to broadly define the differences between in vitro consortia and the communities from which they are derived. In this study we characterized microbial community development in a twin-vessel single-stage chemostat model of the human distal gut ecosystem using both gel (Denaturing Gradient Gel Electrophoresis) and phylogenetic microarray (Human Intestinal Tract Chip) based techniques. Five different sets of twin-vessels were inoculated with feces from three different healthy adult donors and allowed to reach steady state compositions. We found that twin-vessel single-stage chemostats could develop and maintain stable, diverse, and reproducible communities that reach steady state compositions in all five runs by at most 36 days post-inoculation. As noted in other in vitro studies, steady state communities were enriched in Bacteroidetes but not Clostridium cluster XIVa, Bacilli or other Firmicutes relative to the fecal inocula. Communities developed within this model had higher within-run reproducibility than between-run repeatability when using consecutive fecal donations. Both fecal inocula and steady state chemostat communities seeded with feces from different donors had distinct compositions. We conclude that twin-vessel single-stage chemostat models represent a valid simulation of the human distal gut environment and can support complex, representative microbial communities ideal for experimental manipulation
Gut-derived short-chain fatty acids are vividly assimilated into host carbohydrates and lipids
Besten, G. den; Lange, K. ; Havinga, R. ; Dijk, T.H. van; Gerding, A. ; Eunen, K. van; Müller, M.R. ; Groen, A.K. ; Hooiveld, G.J.E.J. ; Bakker, B.M. ; Reijngoud, D.J. - \ 2013
American Journal of Physiology. Gastrointestinal and Liver Physiology 305 (2013)G900-G910. - ISSN 0193-1857
isolated rat hepatocytes - hepatic glucose-production - distal ulcerative-colitis - insulin-resistance - butyrate formation - epithelial-cells - human colon - metabolism - mice - acetate
Acetate, propionate and butyrate are the main short-chain fatty acids (SCFAs) that arise from the fermentation of fibers by the colonic microbiota. While many studies focus on the regulatory role of SCFAs, their quantitative role as a catabolic or anabolic substrate for the host has received relatively little attention. To investigate this aspect, we infused conscious mice with physiological quantities of stable isotopes [1-13C]acetate, [2-13C]propionate or [2,4-13C2]butyrate directly into the cecum, which is the natural production site in mice, and analyzed their interconversion by the microbiota as well as their metabolism by the host. Cecal interconversion - pointing to microbial cross-feeding - was high between acetate and butyrate, low between butyrate and propionate and almost absent between acetate and propionate. As much as 62% of infused propionate was used in whole-body glucose production, in line with its role as gluconeogenic substrate. Conversely, glucose synthesis from propionate accounted for 69% of total glucose production. The synthesis of palmitate and cholesterol in the liver was high from cecal acetate (2.8% and 0.7%, respectively) and butyrate (2.7% and 0.9%, respectively) as substrates, but low or absent from propionate (0.6% and 0.0%, respectively). Label incorporation due to chain elongation of stearate was approximately 8-fold higher than de novo synthesis of stearate. Microarray data suggested that SCFAs exert only a mild regulatory effect on the expression of genes involved in hepatic metabolic pathways during the 6h infusion period. Altogether, gut-derived acetate, propionate and butyrate play important roles as substrates for glucose, cholesterol and lipid metabolism.
Intestinal colonization: How key microbial players become established in this dynamic process: Microbial metabolic activities and the interplay between the host and microbes
Aidy, S.F. El; Abbeele, P. van den; Wiele, T. van der; Louis, P. ; Kleerebezem, M. - \ 2013
Bioessays 35 (2013)10. - ISSN 0265-9247 - p. 913 - 923.
sulfate-reducing bacteria - butyrate-producing bacteria - chain fatty-acids - inflammatory bowel diseases - human gut microbiota - human colon - ulcerative-colitis - hydrogen-sulfide - immune-system - human feces
In this review, we provide an overview of the dynamic changes within the microbiota and its metabolites that are implicated in establishing and maintaining gastrointestinal homeostasis during various stages of microbial colonization. The gradual conversion of the gut microbiota toward a mutualistic microbial community involves replacement of pioneer gut colonizers with bacterial taxa that are characteristic for the adult gut. An important microbial signature of homeostasis in the adult gut is the prevalence and activity of a diverse spectrum of bacterial species that produce beneficial metabolites through metabolic interactions between microbial groups. Deciphering these microbial signatures and their metabolites that govern short and long-term equilibrium, as well as imbalances in host-microbial relationships, may provide novel diagnostic tools and/or therapeutic targets for specific disorders associated with intestinal dysbiosis and loss of homeostasis.
Glycobiome: Bacteria and mucus at the epithelial interface
Ouwerkerk, J.P. ; Vos, W.M. de; Belzer, C. - \ 2013
Best Practice & Research: Clinical Gastroenterology 27 (2013)1. - ISSN 1521-6918 - p. 25 - 38.
inflammatory-bowel-disease - mucosa-associated microbiota - human gut microbiota - abo blood-group - intestinal microbiota - human colon - in-vivo - akkermansia-muciniphila - spatial-organization - bacteroides-thetaiotaomicron
The human gastrointestinal tract is colonised with a dense and diverse microbial community, that is an important player in human health and physiology. Close to the epithelial cells the mucosal microbiota is separated from the host with a thin lining of host derived glycans, including the cell surface glycocalyx and the extracellular secreted mucus. The mucosa-associated microbial composition differs from the luminal content and could be particularly important for nutrient exchange, communication with the host, development of the immune system, and resistance against invading pathogens. The mucosa-associated microbiota has adapted to the glycan rich environment by the production of mucus-degrading enzymes and mucus-binding extracellular proteins, and include mucus-degrading specialists such as Akkermansia muciniphila and Bacteroides thetaiotaomicron. This review is focussed on the host-microbe interactions within the glycan landscape at the epithelial interface and considers the spatial organisation and composition of the mucosa-associated microbiota in health and disease
Iron Depletion and Repletion with Ferrous Sulfate or Electrolytic Iron Modifies the Composition and Metabolic Activity of the Gut Microbiota in Rats
Dostal, A. ; Chassard, C. ; Hilty, F.M. ; Zimmermann, M.B. ; Jaeggi, T. ; Rossi, S. ; Lacroix, C. - \ 2012
The Journal of Nutrition 142 (2012)2. - ISSN 0022-3166 - p. 271 - 277.
bacteroides-fragilis - human colon - butyrate - bacteria - health - flora - requirement - growth - conservation - lactobacilli
Iron (Fe) deficiency anemia is a global health concern and Fe fortification and supplementation are common corrective strategies. Fe is essential not only for the human host but also for nearly all gut bacteria. We studied the impact of Fe deficiency and Fe repletion on the gut microbiota in rats. Weanling rats were fed an Fe-deficient diet for 24 d and then repleted for 13 d with FeSO(4) (n = 15) or electrolytic Fe (n = 14) at 10 and 20 mg Fe . kg diet(-1). In addition, one group of rats (n = 8) received the Fe-deficient diet and one group In = 3) received a Fe-sufficient control diet for all 37 d. Fecal samples were collected at baseline and after the depletion and repletion periods, and colonic tissues were examined histologically. Microbial metabolite composition in cecal water was measured and fecal samples were analyzed for microbial composition with temporal temperature gradient gel electrophoresis and qPCR. Compared to Fe-sufficient rats, Fe-deficient rats had significantly lower concentrations of cecal butyrate (-87%) and propionate (-72%) and the abundance of dominant species was strongly modified, including greater numbers of lactobacilli and Enterobacteriaceae and a large significant decrease of the Roseburia spp./E. rectale group, a major butyrate producer. Repletion with 20 mg FeSO(4) . kg diet(-1) significantly increased cecal butyrate concentrations and partially restored bacterial populations compared to Fe-deficient rats at endpoint. The effects on the gut microbiota were stronger in rats repleted with FeSO(4) than in rats repleted with electrolytic Fe, suggesting ferrous Fe may be more available for utilization by the gut microbiota than elemental Fe. Repletion with FeSO(4) significantly increased neutrophilic infiltration of the colonic mucosa compared to Fe-deficient rats. In conclusion, Fe depletion and repletion strongly affect the composition and metabolic activity of rat gut microbiota. J. Nutr. 142: 271-277, 2012,
Evaluating the microbial diversity of an in vitro model of the human large intestine by phylogenetic microarray analysis
Rajilic-Stojanovic, M. ; Maathuis, A. ; Heilig, G.H.J. ; Venema, K. ; Vos, W.M. de; Smidt, H. - \ 2010
Microbiology 156 (2010). - ISSN 1350-0872 - p. 3270 - 3281.
continuous-culture system - 16s ribosomal-rna - gastrointestinal-tract microbiota - gradient gel-electrophoresis - human colon - human gut - fecal bacteria - retention time - fermentation - communities
A high-density phylogenetic microarray targeting small subunit rRNA (SSU rRNA) sequences of over 1000 microbial phylotypes of the human gastrointestinal tract, the HITChip, was used to assess the impact of faecal inoculum preparation and operation conditions on an in vitro model of the human large intestine (TIM-2). This revealed that propagation of mixed faecal donations for the production of standardized inocula has only a limited effect on the microbiota composition, with slight changes observed mainly within the Firmicutes. Adversely, significant shifts in several major groups of intestinal microbiota were observed after inoculation of the in vitro model. Hierarchical cluster analysis was able to show that samples taken throughout the inoculum preparation grouped with microbiota profiles observed for faecal samples of healthy adults. In contrast, the TIM-2 microbiota was distinct. While members of the Bacteroidetes and some groups within the Bacilli were increased in TIM-2 microbiota, a strong reduction in the relative abundance of other microbial groups, including Bifidobacterium spp., Streptococcus spp., and Clostridium clusters IV and XIVa, was observed. The changes detected with the HITChip could be confirmed using denaturing gradient gel electrophoresis (DGGE) of SSU rRNA amplicons
Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians
Biagi, E. ; Nylund, L. ; Candela, M. ; Ostan, R. ; Bucci, L. ; Pini, E. ; Nikkïla, J. ; Monti, D. ; Satokari, R.M. ; Franceschi, C. ; Brigidi, P. ; Vos, W.M. de - \ 2010
PLoS ONE 5 (2010)5. - ISSN 1932-6203 - 14 p.
ribosomal-rna gene - real-time pcr - butyrate-producing bacteria - fecal microbiota - eubacterium-limosum - human feces - human longevity - human colon - t-cells - age
BACKGROUND: Age-related physiological changes in the gastrointestinal tract, as well as modifications in lifestyle, nutritional behaviour, and functionality of the host immune system, inevitably affect the gut microbiota, resulting in a greater susceptibility to infections. METHODOLOGY/PRINCIPAL FINDINGS: By using the Human Intestinal Tract Chip (HITChip) and quantitative PCR of 16S rRNA genes of Bacteria and Archaea, we explored the age-related differences in the gut microbiota composition among young adults, elderly, and centenarians, i.e subjects who reached the extreme limits of the human lifespan, living for over 100 years. We observed that the microbial composition and diversity of the gut ecosystem of young adults and seventy-years old people is highly similar but differs significantly from that of the centenarians. After 100 years of symbiotic association with the human host, the microbiota is characterized by a rearrangement in the Firmicutes population and an enrichment in facultative anaerobes, notably pathobionts. The presence of such a compromised microbiota in the centenarians is associated with an increased inflammatory status, also known as inflammageing, as determined by a range of peripheral blood inflammatory markers. This may be explained by a remodelling of the centenarians' microbiota, with a marked decrease in Faecalibacterium prauznitzii and relatives, symbiotic species with reported anti-inflammatory properties. As signature bacteria of the long life we identified specifically Eubacterium limosum and relatives that were more than ten-fold increased in the centenarians. CONCLUSIONS/SIGNIFICANCE: We provide evidence for the fact that the ageing process deeply affects the structure of the human gut microbiota, as well as its homeostasis with the host's immune system. Because of its crucial role in the host physiology and health status, age-related differences in the gut microbiota composition may be related to the progression of diseases and frailty in the elderly population
Microbial functionality in the human intestinal tract
Salonen, A. ; Palva, A. ; Vos, W.M. de - \ 2009
Frontiers in Bioscience 14 (2009). - ISSN 1093-9946 - p. 3074 - 3084.
human gastrointestinal-tract - butyrate-producing bacteria - 16s ribosomal-rna - human gut - human colon - metabolic phenotypes - gene-expression - human feces - health - diversity
The extent of metabolic interactions between symbiotic intestinal microbes and the human host, and their system-wide effects on the host physiology are beginning to be understood. The metabolic capacity encoded by the intestinal microbiome significantly extends that of the host, making many of man's physiological characteristics an outcome of a human-microbe co-metabolism. A detailed characterization of the composition and function of the gut microbial ecosystem is required to foster the understanding of its mechanisms and impact. The most recent research on the intestinal ecosystem is reviewed here, with specific attention to the ecological aspects including the anticipated effects of probiotics and prebiotics. Finally, the post-genomics approaches that advance discovering the functionality of intestinal bacteria are addressed
Microbial communities in the human small intestine - coupling diversity to metagenomics
Booijink, C.C.G.M. ; Zoetendal, E.G. ; Kleerebezem, M. ; Vos, W.M. de - \ 2007
Future Microbiology 2 (2007). - ISSN 1746-0913 - p. 285 - 295.
16s ribosomal-rna - gradient gel-electrophoresis - rdna sequence-analysis - gastrointestinal-tract - molecular analysis - crohns-disease - cephalic-phase - human colon - small-bowel - uncultured microorganisms
The gastrointestinal tract is the main site where the conversion and absorption of food components takes place. The host-derived physiological processes and the residing microorganisms, especially in the small intestine, contribute to this nutrient supply. To circumvent sampling problems of the small intestine, several model systems have been developed to study microbial diversity and functionality in the small intestine. In addition, metagenomics offers novel possibilities to gain insight into the genetic potential and functional properties of these microbial communities. Here, an overview is presented of the most recent insights into the diversity and functionality of the microorganisms in the human gastrointestinal tract, with a focus on the small intestine.
In vivo relevance of two critical levels for NAD(P)H:quinone oxidoreductase (NQO1)-mediated cellular protection against electrophile toxicity found in vitro
Haan, L.H.J. de; Pot, G.K. ; Aarts, J.M.M.J.G. ; Rietjens, I.M.C.M. ; Alink, G.M. - \ 2006
Toxicology in Vitro 20 (2006)5. - ISSN 0887-2333 - p. 594 - 600.
dt-diaphorase - menadione toxicity - quinone toxicity - human colon - cells - nqo1 - reductase - enzymes - lines - sensitivity
NAD(P)H:quinone oxidoreductase (NQO1)-mediated detoxification of quinones is suggested to be involved in cancer prevention. In the present study, using transfected CHO cells, it was demonstrated that the relation between NQO1 activity and the resulting protection against the cytotoxicity of menadione shows a steep dose¿response curve revealing a `lower protection threshold¿ of 0.5 ¿mol DCPIP/min/mg protein and an `upper protection threshold¿ at 1 ¿mol DCPIP/min/mg protein. In an additional in vivo experiment it was investigated how both in vitro critical activity levels of NQO1, relate to NQO1 activities in mice and man, either without or upon induction of the enzyme by butylated hydroxyanisol (BHA) or indole-3-carbinol (I3C). Data from an experiment with CD1 mice revealed that base-line NQO1 levels in liver, kidney, small intestine, colon and lung are generally below the observed `lower protection threshold¿ in vitro, this also holds for most human tissue S-9 samples. To achieve NQO1 levels above this `lower protection threshold¿ will require 5¿20 fold NQO1 induction. Discussion focuses on the relevance of the in vitro NQO1 activity thresholds for the in vivo situation. We conclude that increased protection against menadione toxicity can probably not be achieved by NQO1 induction but should be achieved by other mechanisms. Whether this conclusion also holds for other electrophiles and the in vivo situation awaits further definition of their NQO1 protection thresholds
Dietary fructo-oligosaccharides increase intestinal permeability in rats
Bruggencate, S.J.M. ten; Bovee-Oudenhoven, I.M.J. ; Lettink-Wissink, M.L.G. ; Katan, M.B. ; Meer, R. van der - \ 2005
The Journal of Nutrition 135 (2005)4. - ISSN 0022-3166 - p. 837 - 842.
chain fatty-acids - salmonella-typhimurium - fructo-oligosaccharides - mucin secretion - listeria-monocytogenes - epithelial monolayers - lactic-acid - human colon - large-bowel - bile-salts
We showed previously that fructooligosaccharides (FOS) decrease the resistance to salmonella infection in rats. However, the mechanism responsible for this effect is unclear. Therefore, we examined whether dietary FOS affects intestinal permeability before and after infection with Salmonella enterica serovar Enteritidis. Male Wistar rats were fed restricted quantities of a purified diet that mimicked the composition of a Western human diet. The diet was supplemented with 60 g/kg cellulose (control) or 60 g/kg FOS and with 4 mmol/kg of the intestinal permeability marker chromium EDTA (CrEDTA) (n = 8 or 10). After an adaptation period of 2 wk, rats were orally infected with 108 colony-forming units (cfu) of S. enteritidis. Mucin concentrations in intestinal contents and mucosa were measured fluorimetrically, as markers of mucosal irritation. Intestinal permeability was determined by measuring urinary CrEDTA excretion. Translocation of salmonella was quantified by analysis of urinary nitric oxide metabolites with time. Before infection, FOS increased mucosal lactobacilli and enterobacteria in cecum and colon, but not in the ileum. However, FOS increased cytotoxicity of fecal water and intestinal permeability. Moreover, FOS increased fecal mucin excretion and mucin concentrations in cecal and colonic contents, and in cecal mucosa before infection. After infection, mucin excretion and intestinal permeability in the FOS groups increased even further in contrast to the control group. In addition, FOS increased translocation of salmonella to extraintestinal sites. Thus, FOS impairs the intestinal barrier in rats, as indicated by higher intestinal permeability. Whether these results can be extrapolated to humans requires further investigation.
Dietary fructo-oligosaccharides and inulin decrease resistance of rats to salmonelle: protective role of calcium
Bruggencate, S.J.M. ten; Bovee-Oudenhoven, I.M.J. ; Lettink-Wissink, M.L.G. ; Katan, M.B. ; Meer, R. van der - \ 2004
Gut 53 (2004). - ISSN 0017-5749 - p. 530 - 535.
chain fatty-acids - mucin secretion - listeria-monocytogenes - human colon - bile-acids - typhimurium - translocation - bifidobacteria - oligofructose - colonization
Background: We have shown recently that rapid fermentable fructo-oligosaccharides (FOS) decreased resistance of rats towards salmonella. It is not known whether inulin ( which is fermented more gradually) has similar effects or whether buffering nutrients can counteract the adverse effects of rapid fermentation. Aims: To compare the effects of dietary inulin and FOS on resistance of rats to Salmonella enterica serovar Enteritidis and to determine whether calcium phosphate counteracts the effects of fermentation. Methods: Male Wistar rats (n = 8 per group) were fed a human "Western style diet''. Diets with 60 g/kg cellulose ( control), FOS, or inulin had either a low ( 30 mmol/kg) or high ( 100 mmol/kg) calcium concentration. After an adaptation period of two weeks, animals were orally infected with 26109 colony forming units of Salmonella enterica serovar Enteritidis. Colonisation of salmonella was determined by quantification of salmonella in caecal contents. Translocation of salmonella was quantified by analysis of urinary nitric oxide metabolites in time. Results: Inulin and FOS decreased intestinal pH and increased faecal lactobacilli and enterobacteria. Moreover, both prebiotics increased the cytotoxicity of faecal water and faecal mucin excretion. Both prebiotics increased colonisation of salmonella in caecal contents and enhanced translocation of salmonella. Dietary calcium phosphate counteracted most of the adverse effects of inulin and FOS. Conclusions: Both inulin and FOS impair resistance to intestinal infections in rats. This impairment is partially prevented by dietary calcium phosphate. The results of the present study await verification in other controlled animal and human studies.