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Background: Human milk oligosaccharide supplementation safely modulates fecal bifidobacteria abundance and holds the potential to manage symptoms in irritable bowel syndrome (IBS). Here, we aimed to determine the role of a 4:1 mix of 2′-O-fucosyllactose and lacto-N-neotetraose (2′FL/LNnT) on the modulation of the gut microbiota composition and host mucosal response, as well as the link between the bifidobacteria abundance and metabolite modulation, in IBS patients. Methods: Biological samples were collected from IBS patients (n = 58) at baseline and week 4 post-supplementation with placebo, 5 g or 10 g doses of 2′FL/LNnT. The gut microbiota composition, metabolite profiles and expression of genes related to host mucosal response were determined. Results: Moderate changes in fecal, but not mucosal, microbial composition (β-diversity) was observed during the intervention with higher dissimilarity observed within individuals receiving 10g 2′FL/LNnT compared to placebo. Both fecal and mucosal Bifidobacterium spp. increased after 2′FL/LNnT intake, with increased proportions of Bifidobacterium adolescentis and Bifidobacterium longum. Moreover, the intervention modulated the fecal and plasma metabolite profiles, but not the urine metabolite profile or the host mucosal response. Changes in the metabolite profiles were associated to changes in bifidobacteria abundance. Conclusion: Supplementation with 2′FL/LNnT modulated the gut microbiota, fecal and plasma metabolite profiles, but not the host mucosal response in IBS. Furthermore, the bifidogenic effect was associated with metabolite modulation. Overall, these findings support the assertion that 2′FL/LNnT supplementation modulate the intestinal microenvironment of patients with IBS, potentially related to health.

Objectives: Human milk oligosaccharides (HMOs) impact the intestinal microbiota by increasing beneficial bacteria in infants and adults, and are safe and well tolerated in these age groups. Effects on intestinal microbiota, safety, and digestive tolerance in children have not been, however, assessed. The aims of this trial were to evaluate if HMOs are able to specifically modulate the intestinal microbiota in children, and to assess safety and digestive tolerance.Methods: In this randomized, double-blinded, placebo-controlled trial, 75 children with overweight (including obesity) ages 6 to 12 years were randomized to receive 2 '-fucosyllactose (2 ' FL), a mix of 2 ' FL and lacto-N-neotetraose (Mix), or a glucose placebo orally administrated once per day for 8 weeks.Results: The relative abundance of bifidobacteria increased significantly after 4 (P < 0.001) and 8 (P = 0.025) weeks of intervention in the 2 ' FL-group and after 4 weeks (P = 0.033) in the Mix-group, whereas no change was observed in the placebo group. Compared with placebo, the 2 ' FL-group had a significant increase in bifidobacteria abundance after 4 weeks (P < 0.001) and 8 weeks (P = 0.010) and the Mix-group showed a tendency to increased bifidobacteria abundance after 4 (P = 0.071) and 8 weeks (P = 0.071). Bifidobacterium adolescentis drove the bifidogenic effect in the 2 groups. Biochemical markers indicated no safety concerns, and the products did not induce digestive tolerance issues as assessed by Gastrointestinal Symptoms Rating Scale and Bristol Stool Form Scale.Conclusions: Both 2 ' FL and the Mix beneficially modulate intestinal microbiota by increasing bifidobacteria. Furthermore, supplementation with either 2 ' FL alone or a Mix is safe and well tolerated in children.

Human Milk Oligosaccharides (HMOs) constitute an important, highly abundant part of mothers' milk delivering many health benefits to the neonate. Until recently, limited availability of HMOs has prevented their use in infant nutrition and impeded research into their biological effects. The shift from chemical synthesis to biotechnological manufacturing has made them accessible in quantities and at prices that are within reach for commercial applications, including infant formula. It accelerated the studies in the field of pre-clinical and clinical HMO biology. This review gives a short overview of HMO manufacturing from the design and optimization of the microbial cell factory and the production of HMOs in the industrial fermentation process to the purification in the downstream process necessary to obtain a final product. Moreover, the transition from chemistry to biotechnology and the current regulatory landscape and commercialization progress are briefly reviewed.

Human milk oligosaccharides (HMOs) are non-digestible and structurally diverse complex carbohydrates that are highly abundant in human milk. To date, more than 200 different HMO structures have been identified. Their concentrations in human milk vary according to various factors such as lactation period, mother’s genetic secretor status, and length of gestation (term or preterm). The objective of this review is to assess and rank HMO concentrations from healthy mothers throughout lactation at a global level. To this aim, published data from pooled (secretor and non-secretor) human milk samples were used. When samples were reported as secretor or non-secretor, means were converted to a pooled level, using the reported mean of approximately 80/20% secretor/non-secretor frequency in the global population. This approach provides an estimate of HMO concentrations in the milk of an average, healthy mother independent of secretor status. Mean concentrations of HMOs were extracted and categorized by pre-defined lactation periods of colostrum (0–5 days), transitional milk (6–14 days), mature milk (15–90 days), and late milk (>90 days). Further categorizations were made by gestational length at birth, mother’s ethnicity, and analytical methodology. Data were excluded if they were from preterm milk, unknown sample size and mothers with any known disease status. A total of 57 peer-reviewed articles reporting individual HMO concentrations published between 1996 and 2020 were included in the review. Pooled HMO means reported from 31 countries were analyzed. In addition to individual HMO concentrations, 12 articles reporting total HMO concentrations were also analyzed as a basis for relative HMO abundance. Total HMOs were found as 17.7 g/L in colostrum, 13.3 g/L in transitional milk, and 11.3 g/L in mature milk. The results show that HMO concentrations differ largely for each individual HMO and vary with lactation stages. For instance, while 2′-FL significantly decreased from colostrum (3.18 g/L ± 0.9) to late milk (1.64 g/L ± 0.67), 3-FL showed a significant increase from colostrum (0.37 g/L ± 0.1) to late milk (0.92 g/L ± 0.5). Although pooled human milk contains a diverse HMO profile with more than 200 structures identified, the top 10 individual HMOs make up over 70% of total HMO concentration. In mature pooled human milk, the top 15 HMOs in decreasing order of magnitude are 2′-FL, LNDFH-I (DFLNT), LNFP-I, LNFP-II, LNT, 3-FL, 6′-SL, DSLNT, LNnT, DFL (LDFT), FDS-LNH, LNFP-III, 3′-SL, LST c, and TF-LNH.

Human milk oligosaccharides (HMOs) shape the gut microbiota in infants by selectively stimulating the growth of bifidobacteria. Here, we investigated the impact of HMOs on adult gut microbiota and gut barrier function using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME&reg, ), Caco2 cell lines, and human intestinal gut organoid-on-chips. We showed that fermentation of 2&rsquo, O-fucosyllactose (2&rsquo, FL), lacto-N-neotetraose (LNnT), and combinations thereof (MIX) led to an increase of bifidobacteria, accompanied by an increase of short chain fatty acid (SCFA), in particular butyrate with 2&rsquo, FL. A significant reduction in paracellular permeability of FITC-dextran probe was observed using Caco2 cell monolayers with fermented 2&rsquo, FL and MIX, which was accompanied by an increase in claudin-8 gene expression as shown by qPCR, and a reduction in IL-6 as determined by multiplex ELISA. Using gut-on-chips generated from human organoids derived from proximal, transverse, and distal colon biopsies (Colon Intestine-Chips), we showed that claudin-5 was significantly upregulated across all three gut-on-chips following treatment with fermented 2&rsquo, FL under microfluidic conditions. Taken together, these data show that, in addition to their bifidogenic activity, HMOs have the capacity to modulate immune function and the gut barrier, supporting the potential of HMOs to provide health benefits in adults.

Objectives Human milk oligosaccharides safely and beneficially impact bifidobacteria abundance in healthy adults, while their effects in patients with irritable bowel syndrome (IBS) are unknown. Hence, we aimed to determine the dose of 4:1 mix of 2'-O-fucosyllactose and Lacto-N-neotetraose (2'FL/LNnT) that increases fecal bifidobacteria abundance without aggravating overall gastrointestinal symptoms in IBS patients in a randomized, double-blind, controlled study. Additionally, the impact of 2'FL/LNnT on the fecal bacterial profile was assessed. Methods Irritable bowel syndrome patients diagnosed according to the Rome IV criteria received placebo (glucose), or 5 g or 10 g 2'FL/LNnT for 4 weeks followed by a four-week follow-up period. Gastrointestinal Symptom Rating Scale-IBS was used to assess gastrointestinal symptom severity; fecal microbiota composition was evaluated by GA-map™ Dysbiosis Test. Results Of the included 60 patients, two (one placebo and one 10 g) discontinued prematurely. Fecal bifidobacteria abundance was increased at week 4, but not at week 8, in the 10 g group compared to the other groups. Severity of overall or individual gastrointestinal symptoms did not differ between the groups at week 4 or 8, and no symptom deterioration was seen in any of the groups. The 10 g dose influenced overall fecal microbiota composition, and responders-defined as bifidobacteria increase ≥50%-could be discriminated from non-responders based on fecal microbiota modulation. Conclusions The 10 g dose of 2'FL/LNnT induced an increase in the beneficial Bifidobacterium spp. without aggravating gastrointestinal symptoms in patients with IBS. This approach may be worthwhile to modulate gut microbiota of IBS patients toward a healthier profile.

The gut microbiota has been established as an important player influencing many aspects of human physiology. Breast milk, the first diet for an infant, contains human milk oligosaccharides (HMO) that shape the infant’s gut microbiota by selectively stimulating the growth of specific bacteria, especially bifidobacteria. In addition to their bifidogenic activity, the ability of HMO to modulate immune function and the gut barrier makes them prime candidates to restore a beneficial microbiota in dysbiotic adults and provide health benefits. We conducted a parallel, double-blind, randomised, placebo-controlled, HMO-supplementation study in 100 healthy, adult volunteers, consuming chemically produced 2′-O-fucosyllactose (2′FL) and/or lacto-N-neotetraose (LNnT) at various daily doses and mixes or placebo for 2 weeks. All participants completed the study without premature discontinuation. Supplementation of 2′FL and LNnT at daily doses up to 20 g was shown to be safe and well tolerated, as assessed using the gastrointestinal symptoms rating scale. 16S rRNA sequencing analysis showed that HMO supplementation specifically modified the adult gut microbiota with the primary impact being substantial increases in relative abundance of Actinobacteria and Bifidobacterium in particular and a reduction in relative abundance of Firmicutes and Proteobacteria. This study provides the first set of data on safety, tolerance and impact of HMO on the adult gut microbiota. Collectively, the results from this study show that supplementing the diet with HMO is a valuable strategy to shape the human gut microbiota and specifically promote the growth of beneficial bifidobacteria.

Detailed knowledge about the composition of the intestinal microbiota may be critical to unravel the pathogenesis of ulcerative colitis (UC), a human chronic inflammatory bowel disease, since the intestinal microbes are expected to influence some of the key mechanisms involved in the inflammatory process of the gut mucosa. The aim of this study was to investigate the faecal microbiota in patients either with UC in remission (n=6) or with active disease (n=6), and in healthy controls (n=6). The composition of Gram-negative bacteria and Gram-positive bacteria was examined. Antigenic structures of Gram-negative bacteria such as lipopolysaccharides have been related to the inflammatory responses and pathogenesis of inflammatory bowel disease. Dice cluster analysis and principal component analysis of faecal microbiota profiles obtained by denaturing gradient gel electrophoresis and quantitative PCR, respectively, revealed that the composition of faecal bacteria from UC patients with active disease differed from the healthy controls and that this difference should be ascribed to Gram-negative bacteria. The analysis did not show any clear grouping of UC patients in remission. Even with the relatively low number of subjects in each group, we were able to detect a statistically significant underrepresentation of Lactobacillus spp. and Akkermansia muciniphila in UC patients with clinically active disease compared to the healthy controls. In line with previous communications, we have shown that the microbiota in UC patients with active disease differ from that in healthy controls. Our findings indicate that alterations in the composition of the Gram-negative bacterial population, as well as reduced numbers of lactobacilli and A. muciniphila may play a role in UC.

Alterations in the human gut microbiota caused, for example, by diet, functional foods, antibiotics, or occurring as a function of age are now known to be of relevance for host health. Therefore, there is a strong need for methods to detect such alterations in a rapid and comprehensive manner. In the present study, we developed and validated a high-throughput real-time quantitative PCR-based analysis platform, termed 'GUt Low-Density Array' (GULDA). The platform was designed for simultaneous analysis of the change in the abundance of 31 different microbial 16S rRNA gene targets in fecal samples obtained from individuals at various points in time. The target genes represent important phyla, genera, species, or other taxonomic groups within the five predominant bacterial phyla of the gut, Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, and Verrucomicrobia and also Euryarchaeota. To demonstrate the applicability of GULDA, analysis of fecal samples obtained from six healthy infants at both 9 and 18 months of age was performed and showed a significant increase over time of the relative abundance of bacteria belonging to Clostridial cluster IV (Clostridia leptum group) and Bifidobacterium bifidum and concurrent decrease in the abundance of Clostridium butyricum and a tendency for decrease in Enterobacteriaceae over the 9-month period.

The commensal bacteria found in the human gut are important for host health, and an unfavorable composition of the gut microbiota can affect the synergistic interaction that exists between microbes and their host. An altered microbial composition is suggested to play a pivotal role in the pathogenesis of ulcerative colitis (UC), an inflammatory bowel disease, and compositional changes have been observed in the colonic microbiota by us as well as by other research groups 1-3. Since bifidobacteria and lactobacilli may excert anti-inflammatory effects, a reduced level of these commensal bacteria may compromise the colon health and favor intestinal inflammation.In this study, selective stimulation of fecal bifidobacteria and lactobacilli from healthy subjects and UC patients in remission or with active disease were investigated using arabino-oligosaccharides (AOS; DP2-10) derived from sugar beet pulp. The fermentative-induced changes were compared to those for fructo-oligosaccharides (FOS), which are known to have a prebiotic effect. The fermentation studies were carried out using a validated small-scale static batch system, and changes in the fecal microbial communities and metabolites were monitored after 24 h by quantitative real-time PCR and short-chain fatty acid analysis. With a few minor exceptions, AOS affected the communities similarly to what was seen for FOS. Quantitative real-time PCR revealed that Bifidobacterium spp. and Lactobacillus spp. were selectively increased after fermentation of AOS or FOS by fecal microbiota derived from UC patients. The stimulation of growth of Lactobacillus spp. and Bifidobacterium spp. was accompanied by a high production of acetate and hence a decrease of pH. The fermentation of AOS may thus help improve the inflammatory conditions in UC patients through stimulation of bacteria eliciting anti-inflammatory responses and through production of acetate.

The side chains of the rhamnogalacturonan I fraction in sugar beet pectin are particularly rich in arabinan moieties, which may be substituted with feruloyl groups. In this work the arabinan-rich fraction resulting from sugar beet pulp based pectin production was separated by Amberlite XAD hydrophobic interaction and membrane separation into four fractions based on feruloyl substitution and arabino-oligosaccharide chain length: short-chain (DP 2-10) and long-chain (DP 7-14) feruloylated and nonferuloylated arabino-oligosaccharides, respectively. HPAEC, SEC, and MALDI-TOF/TOF analyses of the fractions confirmed the presence of singly and doubly substituted feruloylated arabino-oligosaccharides in the feruloyl-substituted fractions. In vitro microbial fermentation by human fecal samples (n = 6 healthy human volunteers) showed a selective stimulation of bifidobacteria by both the feruloylated and the nonferuloylated long-chain arabino-oligosaccharides to the same extent as the prebiotic fructo-oligosaccharides control. None of the fractions stimulated the growth of the potential pathogen Clostridium difficile in monocultures. This work provides a first report on the separation of potentially bioactive feruloylated arabino-oligosaccharides from sugar beet pulp and an initial indication of the potentially larger bifidogenic effect of relatively long-chain arabino-oligosaccharides as opposed to short-chain arabino-oligosaccharides.

Sugar beet pectin was degraded enzymatically and separated by ion exchange chromatography into series of highly purified homogalacturonides and rhamnogalacturonides. MALDI-TOF/TOF mass-spectrometry was used to determine sizes and structural features. The methodology was based on the sequential use of monocomponent enzymes that were selected to target specific substructures in the sugar beet pectin. Notably pectin lyase and rhamnogalacturonan I lyase were used, which allowed detection of the resulting cleavage products by UV spectroscopy. Seven different homogalacturonides (HG) with degrees of polymerization (DP) from 2 to 8 and six different rhamnogalacturonide (RGI) structures, ranging from DP4 to 6 with defined galactose substitutions were purified. Total recoveries of 200 mg homogalacturonides and 67 mg rhamnogalacturonides per gram sugar beet pectin were obtained. This integrated biorefining method provides an option for advanced upgrading of sugar beet pectin into HG and RGI oligosaccharides of defined size and structure. In vitro microbial fermentation by human faecal samples (n = 9) showed a different response to the DP4 and DP5 HG structures on the ratio between Bacteroidetes and Firmicutes. This indicates that pectic oligosaccharides with only slightly different structures have significantly different biological effects. This is the first report of pectic oligosaccharide activity on gut bacterial populations related to the metabolic syndrome associated with obesity.

Potato pulp is a poorly utilized, high-volume co-processing product resulting from industrial potato starch manufacturing. Potato pulp mainly consists of the tuber plant cell wall material and is particularly rich in pectin, notably galactan branched rhamnogalacturonan I type pectin which has previously been shown to exhibit promising properties as dietary fiber. The objective of this study was to solubilize dietary fibers from potato pulp by a one-step minimal treatment procedure and evaluate the prebiotic potential of the fibers. Statistically designed experiments were conducted to investigate the influence of enzyme type, dosage, substrate level, incubation time, and temperature on the enzyme catalyzed solubilization to define the optimal minimal enzyme treatment for maximal fiber solubilization. The result was a method that within 1 min released 75% [weight/weight (w/w)] dry matter from 1% (w/w) potato pulp treated with 1.0% (w/w) [enzyme/substrate (E/S)] pectin lyase from Aspergillus nidulans and 1.0% (w/w) E/S polygalacturonase from Aspergillus aculeatus at pH 6.0 and 60 °C. Molecular size fractionation of the solubilized fibers revealed two major fractions: one fraction rich in galacturonic acid of 10–100 kDa indicating mainly homogalacturonan, and a fraction >100 kDa rich in galactose, presumably mainly made up of β-1,4-galactan chains of rhamnogalacturonan I. When fermented in vitro by microbial communities derived from fecal samples from three healthy human volunteers, both of the solubilized fiber fractions were more bifidogenic than fructo-oligosaccharides (FOS). Notably the fibers having molecular masses of >100 kDa selectively increased the densities of Bifidobacterium spp. and Lactobacillus spp. 2–3 times more than FOS.

Several studies have shown associations between groups of intestinal bacterial or specific ratios between bacterial groups and various disease traits. Meanwhile, little is known about interactions and associations between eukaryotic and prokaryotic microorganisms in the human gut. In this work, we set out to investigate potential associations between common single-celled parasites such as Blastocystis spp. and Dientamoeba fragilis and intestinal bacteria. Stool DNA from patients with intestinal symptoms were selected based on being Blastocystis spp.-positive (B+)/negative (B-) and D. fragilis-positive (D+)/negative (D-), and split into four groups of 21 samples (B+ D+, B+ D-, B- D+, and B- D-). Quantitative PCR targeting the six bacterial taxa Bacteroides, Prevotella, the butyrate-producing clostridial clusters IV and XIVa, the mucin-degrading Akkermansia muciniphila, and the indigenous group of Bifidobacterium was subsequently performed, and the relative abundance of these bacteria across the four groups was compared. The relative abundance of Bacteroides in B- D- samples was significantly higher compared with B+ D- and B+ D+ samples (P

Some lipid hydrolysis products such as medium-chained NEFA (MC-NEFA), sphingosine and monoacylglycerols (MAG) possess antibacterial activity, while others, including oleic acid, are essential for the optimal growth ofLactobacillusspecies. Thus, changes in the concentrations of NEFA and MAG in the distal ileum and colon can potentially selectively modulate the composition of the gut microbiota, especially in early life when lipid absorption efficacy is reduced. As medium-chained fatty acids are enriched in mothers' milk, such effects may be highly relevant during gut colonisation. In the present study, we examined the effect of selected NEFA, MAG and sphingosine on the composition of faecal microbial communities derived from infants aged 2–5 months during a 24 h anaerobicin vitrofermentation. We tested lipid mixtures in the concentration range of 0–200 μm, either based on MC-NEFA (10 : 0 to 14 : 0 and MAG 12 : 0) or long-chained NEFA (LC-NEFA; 16 : 0 to 18 : 1 and MAG 16 : 0) with and without sphingosine, representing lipid hydrolysis products characteristic for intestinal hydrolysis of breast milk lipids. Ion Torrent sequencing of the bacterial16Sribosomal RNA gene revealed that the relative abundance of lactic acid-producing genera, includingLactobacillusandBifidobacterium, was generally increased in the presence of 50 μmor higher concentrations of MC-NEFA. ForBifidobacterium, the same effect was also observed in the presence of a mixture containing LC-NEFA with sphingosine. On the contrary, the relative abundance of Enterobacteriaceae was significantly decreased in the presence of both lipid mixtures. Our findings suggest that the high concentration of medium-chained fatty acids in breast milk might have functional effects on the establishment of the gut microbiota in early life.

Wholegrain rye has been associated with decreased hunger sensations. This may be partly mediated by colonic fermentation. Sustained consumption of fermentable components is known to change the gut microflora and may increase numbers of saccharolytic bacteria.To investigate the effect of wholegrain rye consumption on appetite and colonic fermentation after a subsequent meal.In a randomized, controlled, three-arm cross-over study, twelve healthy male subjects consumed three iso-caloric evening test meals. The test meals were based on white wheat bread (WBB), wholegrain rye kernel bread (RKB), or boiled rye kernels (RK). Breath hydrogen excretion and subjective appetite sensation were measured before and at 30 min intervals for 3 h after a standardized breakfast in the subsequent morning. After the 3 h, an ad libitum lunch meal was served to assess energy intake. In an in vitro study, RKB and RK were subjected to digestion and 24 h-fermentation in order to study SCFA production and growth of selected saccharolytic bacteria.The test meals did not differ in their effect on parameters of subjective appetite sensation the following day. Ad libitum energy intake at lunch was, however, reduced by 11% (P 0.01) after RKB and 7% (P 0.05) after RK compared with after WWB evening meal. Breath hydrogen excretion was significantly increased following RKB and RK evening meals compared with WWB (P 0.01 and P 0.05, respectively). Overall, RKB and RK were readily fermented in vitro and exhibited similar fermentation profiles, although total SCFA production was higher for RK compared with RKB (P 0.001). In vitro fermentation of RKB and RK both increased the relative quantities of Bifidobacterium and decreased Bacteroides compared with inoculum (P 0.001). The C. coccoides group was reduced after RKB (P 0.001).Consumption of wholegrain rye products reduced subsequent ad libitum energy intake in young healthy men, possibly mediated by mechanisms related to colonic fermentation.

Prebiotic oligosaccharides are defined by their selective stimulation of growth and/or activity of bacteria in the digestive system in ways claimed to be beneficial for health. However, apart from the short chain fatty acids, little is known about bacterial metabolites created by fermentation of prebiotics, and the significance of the size of the oligosaccharides remains largely unstudied.By in vitro fermentations in human fecal microbial communities (derived from six different individuals), we studied the effects of high-mass (HA, >1 kDa), low-mass (LA, All tested carbohydrate sources resulted in a significant increase of Bifidobacterium spp. between 1.79 fold (HA) and 1.64 fold (FOS) in the microbial populations after fermentation, and LC–MS analysis suggested that the bifidobacteria contributed to decomposition of the arabino-oligosaccharide structures, most pronounced in the HA fraction, resulting in release of the essential amino acid phenylalanine. Abundance of Lactobacillus spp. correlated with the presence of a compound, most likely a flavonoid, indicating that lactobacilli contribute to release of such health-promoting substances from plant structures.Additionally, the combination of qPCR and LC–MS revealed a number of other putative interactions between intestinal microbes and the oligosaccharides, which contributes to the understanding of the mechanisms behind prebiotic impact on human health.

The present study aimed at examining oligosaccharides (OS) for potential stimulation of probiotic bacteria. Nineteen structurally well-defined candidate OS covering groups of β-glucosides, α-glucosides and α-galactosides with degree of polymerization 2–4 were prepared in >100 mg amounts by chemoenzymatic synthesis (i.e. reverse phosphorolysis or transglycosylation). Fourteen of the OS are not naturally occurring and five (β-D-glucosyl-fructose, β-D-glucosyl-xylitol, α-glucosyl-(1,4)-D-mannose, α-glucosyl-(1,4)-D-xylose; α-glucosyl-(1,4)-L-fucose) have recently been synthesized for the first time. These OS have not been previously tested for effects of bacterial growth and here the ability of all 19 OS to support growth of four gastrointestinal bacteria: three probiotic bacteria Bifidobacterium lactis, Bifidobacterium longum, and Lactobacillus acidophilus, and one commensal bacterium, Bacteroides vulgatus has been evaluated in monocultures. The disaccharides β-D-glucosyl-xylitol and β-D-glucosyl-(1,4)-xylose noticeably stimulated growth yields of L. acidophilus NCFM, and additionally, β-D-glucosyl-(1,4)-xylose stimulated B. longum Bl-05. α-Glucosyl-(1,4)-glucosamine and α-glucosyl-(1,4)-N-acetyl-glucosamine enhanced the growth rate of B. animalis subsp. lactis and B. longum Bl-05, whereas L. acidophilus NCFM and Bac. vulgatus did not grow on these OS. α-Galactosyl-(1,6)-α-galactosyl-(1,6)-glucose advanced the growth rate of B. animalis subsp. lactis and L. acidophilus NCFM. Thus several of the structurally well-defined OS supported growth of beneficial gut bacteria. This reflects a broad specificity of their sugar transporters for OS, including specificity for non-naturally occurring OS, hence showing promise for design of novel prebiotics.

We compared fecal microbial communities derived either from Ulcerative Colitis (UC) patients in remission (n = 4) or in relapse (n = 4), or from healthy subjects (n = 4). These communities were used for inoculation of a dynamic in vitro gut model, which contained integrated mucin-covered microcosms. We found that the microbiota of the ‘mucus’ largely differed from that of the ‘lumen’. This was partly due to decreased mucus-associated populations of lactic acid producing bacterial populations (LAB), as LAB originating from UC patients had a significantly decreased capacity to colonize the mucin-covered microcosms as compared to those originating from healthy subjects. We found significant differences between the metabolomes of UC patients in relapse and remission, respectively, while the metabolome of patients in remission resembled that of healthy subjects. These novel findings constitute an important contribution to the understanding of the complex etiology of UC.

The mucus layer in the colon, acting as a barrier to prevent invasion of pathogens, is thinner and discontinuous in patients with ulcerative colitis (UC). A recent developed in vitro dynamic gut model, the M-SHIME, was used to compare long-term colonization of the mucin layer by the microbiota from six healthy volunteers (HV) and six UC patients and thus distinguish the mucin adhered from the luminal microbiota. Although under the same nutritional conditions, short-chain fatty acid production by the luminal communities from UC patients showed a tendency toward a lower butyrate production. A more in-depth community analysis of those microbial groups known to produce butyrate revealed that the diversity of the Clostridium coccoides/Eubacterium rectale and Clostridium leptum group, and counts of Faecalibacterium prausnitzii were lower in the luminal fractions of the UC samples. Counts of Roseburia spp. were lower in the mucosal fractions of the UC samples. qPCR analysis for butyryl-CoA:acetate CoA transferase, responsible for butyrate production, displayed a lower abundance in both the luminal and mucosal fractions of the UC samples. The M-SHIME model revealed depletion in butyrate producing microbial communities not restricted to the luminal but also in the mucosal samples from UC patients compared to HV.