Johan E.T. van Hylckama Vlieg’s research while affiliated with Kaleido Biosciences and other places

What is this page?


This page lists works of an author who doesn't have a ResearchGate profile or hasn't added the works to their profile yet. It is automatically generated from public (personal) data to further our legitimate goal of comprehensive and accurate scientific recordkeeping. If you are this author and want this page removed, please let us know.

Publications (10)


Structural analysis of SG10
a, Log2 fold-change in the fractional abundance of bacterial taxa (genus level) in ex vivo cultures of human fecal samples in medium supplemented with the indicated SG preparations. Each point represents the mean of triplicate fermentations from one of five human donor communities; the shape of each point signifies the fecal community. The central bar in the box plot represents the median, the hinges represent the first and third quartiles, and the box plot whiskers represent data points within 1.5 times the interquartile range. b, Glycosyl linkage analysis of SG10. Each data point represents an independent sample preparation (n = 3). Bars represent the mean. Error bars represent the s.d. c, Anomeric region of a 2D (¹H,¹³C)-HSQC NMR spectra of SG10. Linkages joined by beta anomeric bonds are expected to have ¹³C chemical shifts (F1 axis) of 97–102 ppm based on previous literature15–17.
Source data
Absolute abundances of selected bacteria in gnotobiotic mice
a, Data from cecal contents. Each data point represents a single mouse (n = 8). Bars represents the mean. Error bars represent the s.d. Color denotes treatment group. P values were calculated using a one-way ANOVA and are FDR-corrected. b, Fecal data. Each point represents a single mouse (n = 8). Bars represents the mean. Error bars represent the s.d. Shaded regions highlight timepoints during SG10 supplementation. P values were calculated using a linear mixed-effects model (Gaussian) and are FDR-corrected.
Quantification of short-chain fatty acids in mouse cecal contents
The central bar in the box plot represents the median, the hinges represent the first and third quartiles, and the box plot whiskers represent data points within 1.5 times the interquartile range. Each data point represents a single mouse (n = 8 animals). Color denotes treatment group. P values were calculated using a one-way ANOVA with Tukey’s HSD (confidence level = 0.95).
Source data
Expression of PULs containing genes orthologous to genes in B. intestinalis PUL8
a, Summary of the CAZyme content of the 17 Bacteroides present in the 92-member bacterial consortium initially introduced into mice by oral gavage (of which 56 satisfied our criteria for colonization). Annotated glycosyltransferases were omitted from this analysis as they contribute to glycan biosynthesis as opposed to glycan breakdown. b, Summary of top 10 SG10-responsive PULs as determined by GSEA NES score. Substrate predictions are based on orthology to enzymatically characterized CAZy family members plus PUL orthology to experimentally characterized PULs in other Bacteroides. Dot size represents FDR-corrected P values calculated by fgsea³⁴. ‘-‘ indicates no substrate prediction made. a; see text for further discussion of BACINT:PUL8. c, Summary of PUL expression in mice consuming the base HiSF-LoFV diet with or without SG10 supplementation. Expression was defined by average susC/D-like gene TPM (transcripts per million) on a per organism basis (n = 8 mice/diet condition).
Characterization of SG10 released from MFABs with ammonium hydroxide
a, Percentage of SG10 released from SG10-MFABs subjected to chemical release with ammonium hydroxide for varying periods of time at 70 °C. The absolute mass of arabinose remaining on the bead surface at each time point was determined by monosaccharide composition analysis and normalized to the mass of arabinose on the surface of input beads. Each point represents an independent sample preparation from a single sample of MFABs (n = 3 (or 5 for 3.5 hour time point)). The line intersects the mean at each time point. Error bars represent the s.d. b, MALDI mass spectrum of SG10 released from MFABs. Each adjacent peak represents an additional arabinose monomer. The sodium adducts of select arabinose oligosaccharides are denoted above the peaks (DPmer). c, Proportional abundance of SG10 DPmers in free SG10 or SG10 released from SG10-MFABs. Peak heights are normalized to the most abundant peak in the sample such that the maximum value in each sample equals 1. Lines intersect the proportional abundance of each DPmer in a sample.
Source data

+8

In vivo manipulation of human gut Bacteroides fitness by abiotic oligosaccharides
  • Article
  • Full-text available

October 2024

·

13 Reads

Nature Chemical Biology

·

Zachary W. Beller

·

Megan F. Hill

·

[...]

·

Jeffrey I. Gordon

Synthetic glycans (SGs) containing glycosidic linkages and structures not identified in nature offer a means for deliberately altering microbial community properties. Here pools of SG oligosaccharides were generated via polymerization of monosaccharides and screened for their ability to increase saccharolytic Bacteroides in ex vivo cultures of human fecal samples. A lead SG preparation was orally administered to gnotobiotic mice harboring a consortium of 56 cultured, phylogenetically diverse human gut bacteria and fed a Western diet. The abundances of 3 of 15 Bacteroides strains increased, most prominently B. intestinalis. Underlying mechanisms were characterized by analyzing in vivo expression of the carbohydrate utilization machinery, using retrievable microscopic paramagnetic particles with bound SG oligosaccharides and assaying SG degradation by individual purified B. intestinalis glycoside hydrolases. The results reveal that SGs can selectively co-opt carbohydrate utilization machinery in different human gut Bacteroides and demonstrate a means for identifying artificial carbohydrate structures for targeted bacterial manipulation.

Download

Vaginal Microbiota Transplantation (VMT) for treatment of vaginal dysbiosis without the use of antibiotics – A Double-Blinded Randomized Controlled Trial in healthy women with vaginal dysbiosis

July 2024

·

32 Reads

Here we describe the first double-blinded, randomized, placebo-controlled trial (RCT) on vaginal microbiota transplantation (VMT) without antibiotics in women with both symptomatic and asymptomatic vaginal dysbiosis. Forty-nine women were randomly assigned to VMT or placebo. The trial did not show a significant conversion to our predefined Lactobacillus -dominated microbiome. However, in participants not initially converting, antiseptic pretreatment before a subsequent VMT led to a 50% conversion rate, associated with an anti-inflammatory shift in gene expression. Metagenomic sequencing and strain-level genetic analysis confirmed donor engraftment in five of 10 women who showed microbiome conversion. Extensive exploration of the microbiome, immune response and metadata revealed differences in baseline energy metabolism in participants who later experienced donor engraftment. Treatments for vaginal dysbiosis are urgently needed and given that VMT can lead to donor engraftment and change the vaginal immune profile, future studies should focus on optimizing this treatment for various women’s health diseases.


Antibiotic-free vaginal microbiota transplantation (VMT) changes vaginal microbiota and immune profile in women with asymptomatic dysbiosis – reporting of a randomized, placebo-controlled trial

June 2024

·

31 Reads

Here, we describe the first placebo-controlled trial of vaginal microbiota transplantation (VMT) in women with asymptomatic dysbiosis without the use of antibiotic pretreatment. Importantly, we also describe the implementation of a donor program and banking of donor cervicovaginal secretions (CVS) while retaining sample viability, which is crucial to allow for scale-up and confirmatory quality testing. By metagenome sequencing, we demonstrate that VMT provided a significant increase in combined Lactobacillus species in the active arm and strain-level genetic analysis confirmed Lactobacillus engraftment. Moreover, VMT was well tolerated and showed a good safety profile. Furthermore, a shift toward increased Lactobacillus was associated with a change in the expression profile of genes in the complement pathway to a more anti-inflammatory profile. Vaginal microbial and immune profile restoration using VMT may have a positive impact on a wide range of conditions in women’s health.


Fig. 1: Overview of microbiome composition pre-and post-pregnancy. The first Vaginal Microbiota Transplantation (VMT) was administered in September 2021 and resulted in rapid resolution of dysbiosis and Lactobacillus crispatus-dominance (pre-pregnancy period from days 7-153 after VMT). In February 2022 the patient became pregnant. In gestational week six, the microbiome analysis revealed 41.8% of Gardnerella spp., at which time a second VMT with CVS from the same donor was planned two weeks later. Analysis of the vaginal sample taken on the day of the 2nd VMT (+224 days post-VMT, marked in bold letters) revealed that the patient had converted back to a L. crispatus-dominance already prior to the 2nd VMT.
Fig. 2: Comparison of donor and control microbiome. (A) Heatmap illustrating pairwise Manhattan distances between Single Nucleotide Variant (SNV) profiles generated from metagenomic sequencing of CVS samples. The distance scale indicates close to distant profiles from black to white respectively. The times on the recipient samples refer to the time they were collected since the initial VMT. The donor samples include two samples obtained from the same individual donor and were used for VMT at two different time points (see text), Administration 1 and 2, as well as three other samples from three separate individuals that were not used for VMT, Control 1, 2 and 3. The heatmap was performed in https://metasnv.embl.de. (B) Line graph illustrating specific longitudinal trends of the same pairwise Manhattan distances between SNV profiles used to generate the heatmap (Fig. 2A). The horizontal axis labels refer to the time since the first VMT administration, at which samples were collected for metagenomic sequencing. The vertical axis indicates close to distant profiles from low to high respectively. Each line illustrates the pairwise distance between the recipient samples and different individual donor samples over time. Samples obtained from the same individual that were used for VMT are labeled Administration 1 and 2, and three other samples from three separate individuals that were not used for VMT are labeled as Control 1, 2 and 3.
Overview of symptoms, pH measurements and cervical length (only in pregnancy) measurements before pregnancy and in pregnancy.
Antibiotic-free vaginal microbiota transplant with donor engraftment, dysbiosis resolution and live birth after recurrent pregnancy loss: a proof of concept case study

June 2023

·

87 Reads

·

24 Citations

EClinicalMedicine

Background: Vaginal dysbiosis covers imbalances in the vaginal microbiota, defined by altered composition of bacteria, viruses, and fungi and is associated with euploid pregnancy losses, premature birth, infertility, or bacterial vaginosis. A large proportion of women who have vaginal dysbiosis do not experience any symptoms. Antibiotics are the traditional treatment, recently combined with local probiotics in some cases. Vaginal Microbiota Transplantation (VMT) with eubiotic vaginal bacterial microbiota after antibiotic eradication of pathogens has successfully been performed in a case study with five patients, but no VMT has been performed without the use of antibiotics. Methods: This is a proof of concept case study. The patient was found to have vaginal dysbiosis at the RPL clinic at Copenhagen University Hospital Hvidovre, Denmark on the 23rd of June 2021. She was offered and accepted to receive experimental treatment in the form of a VMT as a compassionate use case. VMT is the transfer of cervicovaginal secretions (CVS) from a healthy donor with a Lactobacillus-dominant vaginal microbiome to a recipient with a dysbiotic vaginal microbiome. CVS is a mixture of e.g., mucus, bacteria, metabolites present in the vaginal canal. Potential donors were thoroughly screened for the absence of STIs, and the most suitable donor sample for the specific patient in this study was determined via an in vitro microbiome competition assay. Findings: A 30-year-old patient with one livebirth and a complicated pregnancy history of two stillbirths and 1 s trimester pregnancy loss in gestational weeks 27 (2019), 17 (2020) and 23 (2020) respectively with complaints of vaginal irritation and discharge that had aggravated in all her pregnancies. Her vaginal microbiome composition showed a 90% dominance of Gardnerella spp. After one VMT there was a complete shift in microbiome composition to 81.2% L. crispatus and 9% L. jensenii with a concurrent resolvement of vaginal symptoms. Single nucleotide polymorphism-analysis confirmed her microbiome to be of donor origin and it remain stable now 1.5 years after the VMT. Five months after the VMT she became pregnant and has successfully delivered a healthy baby at term. Interpretation: Here we report a successful VMT with confirmed donor strain engraftment followed by a successful pregnancy and delivery after a series of late pregnancy losses/stillbirths. Findings suggest that VMT is a potential treatment for severe vaginal dysbiosis. Further, larger studies are required. Funding: The study was partially funded (i.e., analysis costs) by Freya Biosciences Aps, Fruebjergvej, 2100 Copenhagen, Denmark.


Fig. 1 Analytical pipeline and description of glycan compositions and fermentation dynamics. a Schematic representation of the analytical pipeline. b-f Monosaccharide compositions and fermentation dynamics of 653 SGs and 110 reference glycans. b Percentages of SGs (yellow) and reference glycans (indigo) containing various monosaccharide types. c Number of monosaccharide types composing each SG or reference glycan. d Distribution of weight average molecular weights of SGs measured by SEC. e-g Growth (OD 600 ) and pH dynamics of triplicate fecal cultures fermenting 5 g l −1 of a single SG or reference glycan in MM29 medium. e Hierarchical clustering of glycans into five fermentation groups based on twelve growth and pH parameters. Bars below the dendrogram show compound class: SG (yellow), reference glycan (indigo), or no glycan (magenta). Mean (f) growth and (g) pH curves (±SD) for each glycan fermentation group shown in e. Source data are provided as a Source Data file. SGs Synthetic Glycans, SEC size exclusion chromatography, OD 600 optical density at 600 nm, SD standard deviation, kDa kilodalton.
Fig. 2 Effects of glycans on fecal community metabolic output and taxonomic composition. a Yields of two SCFAs, butyrate and propionate, from fecal cultures fermenting either an SG (yellow circles, n = 653), reference glycan (indigo triangles, n = 110), or no glycan (magenta square). b Maximum gas production rate (psi h −1 ) during fecal culture fermentation of glycans from each of the five fermentation groups in Fig. 1e-g. c Shannon diversity and d species richness of fecal cultures fermenting SGs (yellow, n = 190) versus reference glycans (indigo, n = 40). e Shannon diversity of fecal cultures fermenting BRF or BQM (yellow) is higher than reference glycans (indigo) for all comparisons except BQM versus XOS (Kruskal-Wallis followed by Dunn's comparison test, p < 0.05). f NMDS of metagenomic data calculated based on a matrix of Bray-Curtis dissimilarities using species-level mapping of sequencing reads from fecal cultures grown on either an SG (yellow circles, n = 190), reference glycan (indigo triangles, n = 40), or no glycan (magenta square). g NMDS as in f colored by differences in taxonomic composition defined by eight K-means clusters based on species-level mapping of sequencing reads. Data for each glycan is the mean of (a-d, f, g) three or (e) six replicate fecal cultures grown on 5 g l −1 of each SG or reference glycan for 45 h in MM29 medium. a, f, g BRF and BQM highlighted in red. b-e Box plots show median and interquartile ranges. Asterisks show significance (*p < 0.05, **p < 0.01) by b Tukey's test or c, d two-sided Wilcoxon rank-sum test. Source data are provided as a Source Data file. SG Synthetic Glycan, SCFA shortchain fatty acid, XOS xylo-oligosaccharides, FOS fructo-oligosaccharides, GOS galacto-oligosaccharides, NMDS non-metric multidimensional scaling.
Fig. 3 Enteric pathogen growth in pure culture and relative abundances in fecal communities grown on glycans. Six strains of a Klebsiella pneumoniae, b Escherichia coli, or c Enterococcus faecium were cultured with 5 g l −1 of a single SG (n = 148) or reference glycan (n = 32) in CM3 medium. Data is the mean maximum growth (OD 600 ) of triplicate cultures; strain names are shown above each plot. Fecal communities from a healthy donor were OD 600 -normalized to contain 8% of d K. pneumoniae CDC 003, e E. coli CDC 001, or f E. faecium ATCC 700221 and cultured in triplicate with 5 g l −1 of an SG (n = 45) or reference glycan (n = 17) for 45 h in MM29 medium. The relative abundances of the pathogens were quantified by 16S rRNA gene sequencing. Data points show FOS (indigo circle), BRF (yellow circle), or BQM (orange triangle) cultures. Box plots show median and interquartile ranges. Asterisks show significance (*p < 0.05, **p < 0.01) by two-sided Wilcoxon rank-sum test. Source data are provided as a Source Data file. SGs Synthetic Glycans, OD 600 optical density at 600 nm, FOS fructo-oligosaccharides.
Fig. 6 Glycan effects in mouse models of DSS colitis and C. difficile infection. a-d Mice were treated in drinking water with 2.5% DSS (days 0-5, dashed lines) and 1% (v/v) glycans (days 7-14), as appropriate. Treatment groups (eight animals per group): −DSS (gray), +DSS (red), +DSS, FOS (indigo), +DSS, BRF (yellow). Treatment group comparisons of (a) body weight, (b) stool score averaged over days 0-14, (c) day 14 endoscopy scores with representative images, and (d) day 14 histology scores with representative 100x magnified H&E stained distal colon micrographs. e-g Mice were treated with antibiotics (days -14-3), infected with C. difficile (day 0), and treated with 50 mg kg −1 vancomycin daily (days 0-4) or 1% (v/v) glycans in drinking water (days 1-6), as appropriate. Treatment groups (12 animals per group): no glycan (gray), vancomycin (green), FOS (indigo), BRF (yellow circles), and BQM (orange triangles). Treatment group comparisons of (e) body weight, (f) survival, and (g) clinical scores. Data in (a, b, e, g) show treatment group means ± SEM. Box plots in (c, d) show median and interquartile range. Data points in (b-d, g) show individual mice. a, e Statistics on body mass changes are based on area under the curve for all individual mice. Asterisks show significance (*p < 0.05, **p < 0.01) by (a-e, g) two-sided Wilcoxon rank-sum test or (f) log-rank test. Source data are provided as a Source Data file. DSS dextran sodium sulfate, FOS fructo-oligosaccharides, ABX antibiotics, CFU colony forming units, SEM standard error of the mean, NS non-significant.
Synthetic glycans control gut microbiome structure and mitigate colitis in mice

December 2022

·

310 Reads

·

37 Citations

Relative abundances of bacterial species in the gut microbiome have been linked to many diseases. Species of gut bacteria are ecologically differentiated by their abilities to metabolize different glycans, making glycan delivery a powerful way to alter the microbiome to promote health. Here, we study the properties and therapeutic potential of chemically diverse synthetic glycans (SGs). Fermentation of SGs by gut microbiome cultures results in compound-specific shifts in taxonomic and metabolite profiles not observed with reference glycans, including prebiotics. Model enteric pathogens grow poorly on most SGs, potentially increasing their safety for at-risk populations. SGs increase survival, reduce weight loss, and improve clinical scores in mouse models of colitis. Synthetic glycans are thus a promising modality to improve health through selective changes to the gut microbiome.




THE SYNTHETIC GLYCAN KB295 OPTIMIZES MICROBIOME COMPOSITION AND FUNCTION IN ULCERATIVE COLITIS – RESULTS FROM A PROOF OF PRINCIPLE HUMAN STUDY

January 2022

·

17 Reads

Inflammatory Bowel Diseases

The pathogenesis of ulcerative colitis (UC) involves genetic susceptibility, immune-mediated tissue injury and environmental factors including disturbances of the gut microbiota. Nearly all current approved therapies modify host immunity, rather than directly targeting the microbiota. Fecal microbiota transplantation provides encouraging evidence for the therapeutic potential of gut microbiome modulation. Bacteria in the GI tract are ecologically differentiated by their ability to use specific glycans as growth substrates, making glycans a promising and safe alternative to target the microbiome. To explore this, we used an ex vivo fecal microbiota culture system to identify a synthetic glycan (KB295) with desirable microbiological activity and conducted a proof of principle study of safety and tolerability of KB295 in patients with UC. Fecal microbial communities from healthy subjects were incubated anaerobically with and without (negative control) KB295. KB295 increased short chain fatty acid (SCFA) production across ten fecal samples to a median concentration of 47.0 mM compared to 15.2 mM with the negative control in culture supernatants, including increases in acetate, propionate, and butyrate in all cases. Metagenomic sequencing of the ex vivo fecal pellets revealed that KB295 depleted pathobionts in the family Enterobacteriaceae to a median relative abundance of 10.8% compared to 38.2% with the negative control. Pathobiont depletion was associated with enrichments of diverse genera in the phyla Bacteroidetes and Firmicutes. Twelve patients with mild to moderate UC were enrolled in an open-label single-arm study with an 8-week intake of KB295. KB295 was well tolerated with generally mild adverse events, and only one AE resulted in discontinuation. The most frequently occurring adverse events were changes in bowel habit, flatulence, and headache. Fecal calprotectin and lactoferrin decreased by median values of 69.0% (n=11) and 86.0% (n=6), respectively, from screening to the end of the KB295 intake. Consistent with the ex vivo preclinical findings, of the subjects for whom we have data to date, the relative abundance of the fecal pathobiont family Enterobacteriaceae decreased from five participants, and the commensal genus Parabacteroides was enriched in four of five participants. These results establish a proof of principle for the glycobiological modulation of gut microbiome composition and function and provide insight into the potential utility of this strategy in patients with ulcerative colitis. The safety, tolerability, and encouraging evidence for reduced inflammation with KB295 call for a Phase 2 study, which is planned.


Figure 1. Primary and secondary end points. (A) Mean Lewis score per visit. (B) The primary end point mean Lewis score AUC ± standard error of the mean per treatment arm. (C) Median number of ulcers per visit. (D) The secondary end point ulcer number AUC ± standard error of the mean per treatment arm. *P < .05. Effects sizes were (B) 30% lower AUC in the Bif195 arm and (D) 33% lower AUC in the Bif195 arm.
Figure 2. Tertile stratification of ulceration. (A, C, and E) Median ulcer numbers per visit and (B, D, and F) mean ulcer number AUC ± standard error of the mean from VCE stratified on small intestine tertiles (thirds of small intestine). *P < .05.
Figure 3. (A) Mean serum concentrations of PGE 2 per visit and (B) AUC ± standard error of the mean. Mean serum concentrations of (C) TXB2 per visit and (D) AUC ± standard error of the mean.
Overview of Trial Adverse Events
Bifidobacterium breve Bif195 Protects Against Small-Intestinal Damage Caused by Acetylsalicylic Acid in Healthy Volunteers

May 2019

·

300 Reads

·

60 Citations

Gastroenterology

Background & aims: Enteropathy and small-intestinal ulcers are common adverse effects of nonsteroidal anti-inflammatory drugs such as acetylsalicylic acid (ASA). Safe, cytoprotective strategies are needed to reduce this risk. Specific bifidobacteria might have cytoprotective activities, but little is known about these effects in humans. We used serial video capsule endoscopy (VCE) to assess the efficacy of a specific Bifidobacterium strain in healthy volunteers exposed to ASA. Methods: We performed a single-site, double-blind, parallel-group, proof-of-concept analysis of 75 heathy volunteers given ASA (300 mg) daily for 6 weeks, from July 31 through October 24, 2017. The participants were randomly assigned (1:1) to groups given oral capsules of Bifidobacterium breve (Bif195) (≥5 × 1010 colony-forming units) or placebo daily for 8 weeks. Small-intestinal damage was analyzed by serial VCE at 6 visits. The area under the curve (AUC) for intestinal damage (Lewis score) and the AUC value for ulcers were the primary and first-ranked secondary end points of the trial, respectively. Results: Efficacy data were obtained from 35 participants given Bif195 and 31 given placebo. The AUC for Lewis score was significantly lower in the Bif195 group (3040 ± 1340 arbitrary units) than the placebo group (4351 ± 3195) (P = .0376). The AUC for ulcer number was significantly lower in the Bif195 group (50.4 ± 53.1 arbitrary units) than in the placebo group (75.2 ± 85.3 arbitrary units) (P = .0258). Twelve adverse events were reported from the Bif195 group and 20 from the placebo group. None of the events was determined to be related to Bif195 intake. Conclusions: In a randomized, double-blind trial of healthy volunteers, we found oral Bif195 to safely reduce the risk of small-intestinal enteropathy caused by ASA. ClinicalTrials.gov no: NCT03228589.


Understanding mode of action can drive the translational pipeline towards more reliable health benefits for probiotics

April 2019

·

162 Reads

·

64 Citations

Current Opinion in Biotechnology

p>The different levels of knowledge described in a translational pipeline (the connection of molecular mechanisms with pre-clinical physiological and human health effects) are not complete for many probiotics. At present, we are not in a position to fully understand the mechanistic basis of many well established probiotic health benefits which, in turn, limits our ability to use mechanisms to predict which probiotics are likely to be effective in any given population. Here we suggest that this concept of a translation pipeline connecting mechanistic insights to probiotic efficacy can support the selection and production of improved probiotic products. Such a conceptual pipeline would also provide a framework for the design of clinical trials to convincingly demonstrate the benefit of probiotics to human health in well-defined subpopulations.</p

Citations (5)


... Moreover, an emerging method involving microbiota transplantation has been explored for preventing recurrent bacterial vaginosis (Lev-Sagie et al. 2019;Abbe et al. 2023;Wrønding et al. 2023). This approach resembles single or multiple microbial transplants, differing in that subjects receive vaginal lavage from healthy donors, introducing a complete and partially biofilm-associated healthy microbiota (Lev-Sagie et al. 2019;Abbe et al. 2023). ...

Reference:

Multiple-species biofilms as structuralized microbial communities for modulating microbiota homeostasis in human
Antibiotic-free vaginal microbiota transplant with donor engraftment, dysbiosis resolution and live birth after recurrent pregnancy loss: a proof of concept case study

EClinicalMedicine

... https://doi.org/10.1038/s41589-024-01763-6 effects on the relative abundances of bacterial taxa characterized by culture-independent methods 7,14 . In the present study, we examine the mechanisms by which certain human gut Bacteroides respond to a SG preparation in vitro and in gnotobiotic mice. ...

Synthetic glycans control gut microbiome structure and mitigate colitis in mice

... It is suggested that the increased energy production can cause the increase in pyruvic acid via glycolysis in hypoxic conditions induced by these diseases. This, in turn, leads to the accumulation of pyruvates that cannot be used in the tricarboxylic acid cycle [52], and in hypoxic conditions, an excess of pyruvate can induce an overflow of lactate, which causes an acidic environment and dysbiosis [53]. Understanding these metabolic changes can be crucial in determining potential targets for therapeutic intervention to treat UC. ...

THE SYNTHETIC GLYCAN KB295 OPTIMIZES MICROBIOME COMPOSITION AND FUNCTION IN ULCERATIVE COLITIS – RESULTS FROM A PROOF OF PRINCIPLE HUMAN STUDY
  • Citing Article
  • February 2022

Gastroenterology

... A role for the microbiome in NSAID-induced mucosal damage is supported by the finding that in a healthy microbiome, Lactobacillus exerts beneficial health effects, such as protection of the integrity of the colonic epithelium and cell junctions [46]. Experimental rat models have shown that administration of probiotics such as Lactobacillus and Bifidobacterium prevents NSAID-induced enteropathy [47][48][49]. ...

Bifidobacterium breve Bif195 Protects Against Small-Intestinal Damage Caused by Acetylsalicylic Acid in Healthy Volunteers

Gastroenterology

... Probiotics engage with both the host and the microbiome through molecular effectors found on the cell structures or released as metabolic products. Probiotic metabolites can influence the microbiota by engaging in cross-feeding interactions, modifying the gastrointestinal microenvironment, competing for nutrients and binding sites, and inhibiting growth through the production of specific antibacterial compounds like bacteriocins [34]. Regarding host cells, probiotic effector molecules can directly interact with receptors on immune cells, intestinal epithelial cells, vagal afferent fibres and enteroendocrine cells. ...

Understanding mode of action can drive the translational pipeline towards more reliable health benefits for probiotics

Current Opinion in Biotechnology