A decrease in iron availability to human gut microbiome reduces the growth of potentially pathogenic gut bacteria; an in vitro colonic fermentation study

Flavonoids are a major group of dietary plant polyphenols and have a positive health impact, but their modification and degradation in the human gut is still widely unknown. Due to the rise of metagenome data of the human gut microbiome and the assembly of hundreds of thousands of bacterial metagenome-assembled genomes (MAGs), large-scale screening for potential flavonoid-modifying enzymes of human gut bacteria is now feasible. With sequences of characterized flavonoid-transforming enzymes as queries, the Unified Human Gastrointestinal Protein catalog was analyzed and genes encoding putative flavonoid-modifying enzymes were quantified. The results revealed that flavonoid-modifying enzymes are often encoded in gut bacteria hitherto not considered to modify flavonoids. The enzymes for the physiologically important daidzein-to-equol conversion, well studied in Slackiaisoflavoniconvertens, were encoded only to a minor extent in Slackia MAGs, but were more abundant in Adlercreutzia equolifaciens and an uncharacterized Eggerthellaceae species. In addition, enzymes with a sequence identity of about 35% were encoded in highly abundant MAGs of uncultivated Collinsella species, which suggests a hitherto uncharacterized daidzein-to-equol potential in these bacteria. Of all potential flavonoid modification steps, O-deglycosylation (including derhamnosylation) was by far the most abundant in this analysis. In contrast, enzymes putatively involved in C-deglycosylation were detected less often in human gut bacteria and mainly found in Agathobacter faecis (formerly Roseburia faecis). Homologs to phloretin hydrolase, flavanonol/flavanone-cleaving reductase and flavone reductase were of intermediate abundance (several hundred MAGs) and mainly prevalent in Flavonifractor plautii. This first comprehensive insight into the black box of flavonoid modification in the human gut highlights many hitherto overlooked and uncultured bacterial genera and species as potential key organisms in flavonoid modification. This could lead to a significant contribution to future biochemical-microbiological investigations on gut bacterial flavonoid transformation. In addition, our results are important for individual nutritional recommendations and for biotechnological applications that rely on novel enzymes catalyzing potentially useful flavonoid modification reactions.

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Lacticaseibacillus rhamnosus GG and Saccharomyces cerevisiae boulardii supplementation exert protective effects on human gut microbiome following antibiotic administration in vitro

Beneficial Microbes ◽

10.3920/bm2020.0180 ◽

2021 ◽

pp. 1-16

Author(s):

C. Duysburgh ◽

P. Van den Abbeele ◽

M. Morera ◽

M. Marzorati

Keyword(s):

Saccharomyces Cerevisiae ◽

Gut Microbiome ◽

Gastrointestinal Symptoms ◽

Lactobacillus Rhamnosus ◽

Antibiotic Administration ◽

Protective Effects ◽

Human Gut ◽

Human Gut Microbiome ◽

The Impact

Antibiotic-induced dysbiosis of the microbial community has been associated with several gastrointestinal symptoms. The impact of repeated administration of Lacticaseibacillus rhamnosus GG (CNCM-I-4798) (formerly known as Lactobacillus rhamnosus GG), Saccharomyces cerevisiae boulardii (CNCM-I-1079) and their combination (associated in Smebiocta/Smectaflora Protect®) in supporting recovery of gut microbiota functionality and composition during and following amoxicillin:clavulanic acid administration was evaluated in vitro. Antibiotic dosage negatively affected SCFA production, coinciding with detrimental effects on Bacteroidetes, Firmicutes and Bifidobacterium spp. in the simulated proximal colon, while Akkermansia muciniphila was significantly reduced in the distal colon. L. rhamnosus GG and S. boulardii were able to thrive in both colon regions upon dosing, with S. boulardii even showing protective effects on the survival of L. rhamnosus GG during antibiotic administration. The impact of the probiotic strains on microbiome recovery revealed that supplementation with L. rhamnosus GG and/or S. boulardii resulted in a stimulating effect on the most abundant bacterial groups within the bacterial community of each donor. For one of the donors tested, co-dosing of L. rhamnosus GG and S. boulardii resulted in superior short-chain fatty acid recovery accompanied by a stronger increase in abundance of Bifidobacteriaceae. Overall, the current study provides first evidence that combined supplementation of L. rhamnosus GG and S. boulardii might be an interesting candidate in limiting detrimental effects of amoxicillin:clavulanic acid on the human gut microbiome, though further studies are warranted to confirm these findings.

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An in vitro intestinal platform with a self-sustaining oxygen gradient to study the human gut/microbiome interface

Biofabrication ◽

10.1088/1758-5090/ab446e ◽

2019 ◽

Vol 12 (1) ◽

pp. 015006 ◽

Cited By ~ 9

Author(s):

Raehyun Kim ◽

Peter J Attayek ◽

Yuli Wang ◽

Kathleen L Furtado ◽

Rita Tamayo ◽

...

Keyword(s):

Gut Microbiome ◽

Human Gut ◽

Oxygen Gradient ◽

Human Gut Microbiome

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Concentrated Raw Fibers Enhance the Fiber-Degrading Capacity of a Synthetic Human Gut Microbiome

10.20944/preprints202106.0339.v1 ◽

2021 ◽

Author(s):

Alexander Steimle ◽

Mareike Neumann ◽

Erica Grant ◽

Jonathan D Turner ◽

Mahesh S Desai

Keyword(s):

Gut Microbiome ◽

A Priori ◽

Human Gut ◽

In Vivo Models ◽

Human Gut Microbiome ◽

Different Strains ◽

Alpha Glucosidase ◽

Prebiotic Fibers

Consumption of prebiotic fibers to modulate the human gut microbiome is a promising strategy to positively impact health. Nevertheless, given the compositional complexity of the microbiome and its inter-individual variances, generalized recommendations on the source or amount of fiber supplements remain vague. This problem is further compounded by availability of tractable in vitro and in vivo models to validate certain fibers. We employed a gnotobiotic mouse model containing an a priori characterized 14-member synthetic human gut microbiome (SM) for their ability to metabolize a suit of fibers in vitro; the SM contains 14 different strains belonging to five distinct phyla. Since soluble purified fibers have been a common subject of studies, we specifically investigated the effects of concentrated raw fibers (CRFs)—containing fibers from pea, oat, psyllium, wheat and apple—on the compositional and functional alterations in the SM. We demonstrate that, compared to a fiber-free diet, CRF supplementation increased the abundance of fiber-degraders namely Eubacterium rectale, Roseburia intestinalis and Bacteroides ovatus and decreased the abundance of the mucin-degrader Akkermansia muciniphila. These results were corroborated by a general increase of bacterial fiber-degrading α-glucosidase enzyme activity. Overall, our results highlight the ability of CRFs to enhance the microbial fiber-degrading capacity.

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Feeding Bugs to Bugs: Edible Insects Modify the Human Gut Microbiome in an in vitro Fermentation Model

Frontiers in Microbiology ◽

10.3389/fmicb.2020.01763 ◽

2020 ◽

Vol 11 ◽

Cited By ~ 1

Author(s):

Wayne Young ◽

Sai Krishna Arojju ◽

Mark R. McNeill ◽

Elizabeth Rettedal ◽

Jessica Gathercole ◽

...

Keyword(s):

Gut Microbiome ◽

Edible Insects ◽

Human Gut ◽

In Vitro Fermentation ◽

Human Gut Microbiome ◽

Fermentation Model

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Concentrated Raw Fibers Enhance the Fiber-Degrading Capacity of a Synthetic Human Gut Microbiome

International Journal of Molecular Sciences ◽

10.3390/ijms22136855 ◽

2021 ◽

Vol 22 (13) ◽

pp. 6855

Author(s):

Alex Steimle ◽

Mareike Neumann ◽

Erica T. Grant ◽

Jonathan D. Turner ◽

Mahesh S. Desai

Keyword(s):

Gut Microbiome ◽

A Priori ◽

Human Gut ◽

General Increase ◽

In Vivo Models ◽

Human Gut Microbiome ◽

Different Strains ◽

Prebiotic Fibers

The consumption of prebiotic fibers to modulate the human gut microbiome is a promising strategy to positively impact health. Nevertheless, given the compositional complexity of the microbiome and its inter-individual variances, generalized recommendations on the source or amount of fiber supplements remain vague. This problem is further compounded by availability of tractable in vitro and in vivo models to validate certain fibers. We employed a gnotobiotic mouse model containing a 14-member synthetic human gut microbiome (SM) in vivo, characterized a priori for their ability to metabolize a collection of fibers in vitro. This SM contains 14 different strains belonging to five distinct phyla. Since soluble purified fibers have been a common subject of studies, we specifically investigated the effects of dietary concentrated raw fibers (CRFs)—containing fibers from pea, oat, psyllium, wheat and apple—on the compositional and functional alterations in the SM. We demonstrate that, compared to a fiber-free diet, CRF supplementation increased the abundance of fiber-degraders, namely Eubacterium rectale, Roseburia intestinalis and Bacteroides ovatus and decreased the abundance of the mucin-degrader Akkermansia muciniphila. These results were corroborated by a general increase of bacterial fiber-degrading α-glucosidase enzyme activity. Overall, our results highlight the ability of CRFs to enhance the microbial fiber-degrading capacity.

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The Human Gut Microbiome’s Influence on Arsenic Toxicity

Current Pharmacology Reports ◽

10.1007/s40495-019-00206-4 ◽

2019 ◽

Vol 5 (6) ◽

pp. 491-504 ◽

Cited By ~ 2

Author(s):

Michael Coryell ◽

Barbara A. Roggenbeck ◽

Seth T. Walk

Keyword(s):

Gut Microbiome ◽

Arsenic Speciation ◽

Methylation Status ◽

Arsenic Exposure ◽

Health Concern ◽

Current Evidence ◽

Arsenic Toxicity ◽

Human Gut ◽

Human Gut Microbiome

Abstract Purpose of Review Arsenic exposure is a public health concern of global proportions with a high degree of interindividual variability in pathologic outcomes. Arsenic metabolism is a key factor underlying toxicity, and the primary purpose of this review is to summarize recent discoveries concerning the influence of the human gut microbiome on the metabolism, bioavailability, and toxicity of ingested arsenic. We review and discuss the current state of knowledge along with relevant methodologies for studying these phenomena. Recent Findings Bacteria in the human gut can biochemically transform arsenic-containing compounds (arsenicals). Recent publications utilizing culture-based approaches combined with analytical biochemistry and molecular genetics have helped identify several arsenical transformations by bacteria that are at least possible in the human gut and are likely to mediate arsenic toxicity to the host. Other studies that directly incubate stool samples in vitro also demonstrate the gut microbiome’s potential to alter arsenic speciation and bioavailability. In vivo disruption or elimination of the microbiome has been shown to influence toxicity and body burden of arsenic through altered excretion and biotransformation of arsenicals. Currently, few clinical or epidemiological studies have investigated relationships between the gut microbiome and arsenic-related health outcomes in humans, although current evidence provides strong rationale for this research in the future. Summary The human gut microbiome can metabolize arsenic and influence arsenical oxidation state, methylation status, thiolation status, bioavailability, and excretion. We discuss the strength of current evidence and propose that the microbiome be considered in future epidemiologic and toxicologic studies of human arsenic exposure.

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A high-throughput method to characterize the gut bacteria growth upon engineered nanomaterial treatment

Environmental Science Nano ◽

10.1039/d0en00568a ◽

2020 ◽

Vol 7 (10) ◽

pp. 3155-3166

Author(s):

Qin Yang ◽

Tharushi Prabha Keerthisinghe ◽

Tiffany Rou Jie Tan ◽

Xiaoqiong Cao ◽

Magdiel Inggrid Setyawati ◽

...

Keyword(s):

High Throughput ◽

Gut Microbiome ◽

Bacterial Culture ◽

Human Gut ◽

Bacteria Growth ◽

Human Gut Microbiome ◽

Engineered Nanomaterial ◽

High Throughput Method ◽

Pure Bacterial Culture

We developed a DNA-based quantification (DBQ) method in a 96-well plate format. The applicability of this method for several types of ENMs was proved in both pure bacterial culture and in vitro human gut microbiome community.

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Acquired interbacterial defense systems protect against interspecies antagonism in the human gut microbiome

10.1101/471110 ◽

2018 ◽

Cited By ~ 1

Author(s):

Benjamin D. Ross ◽

Adrian J. Verster ◽

Matthew C. Radey ◽

Danica T. Schmidtke ◽

Christopher E. Pope ◽

...

Keyword(s):

Gut Microbiome ◽

Gene Clusters ◽

Protective Capacity ◽

Human Gut ◽

Microbiome Composition ◽

Toxin Resistance ◽

Human Gut Microbiome ◽

Bacterial Antagonism ◽

The Impact

AbstractThe impact of direct interactions between co-resident microbes on microbiome composition is not well understood. Here we report the occurrence of acquired interbacterial defense (AID) gene clusters in bacterial residents of the human gut microbiome. These clusters encode arrays of immunity genes that protect against type VI secretion toxin-mediated intra- and inter-species bacterial antagonism. Moreover, the clusters reside on mobile elements and we demonstrate that their transfer is sufficient to confer toxin resistance in vitro and in gnotobiotic mice. Finally, we identify and validate the protective capacity of a recombinase-associated AID subtype (rAID-1) present broadly in Bacteroidales genomes. These rAID-1 gene clusters have a structure suggestive of active gene acquisition and include predicted immunity factors of toxins deriving from diverse organisms. Our data suggest that neutralization of contact-dependent interbacterial antagonism via AID systems shapes human gut microbiome ecology.

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1774. Ridinilazole (RDZ) for Clostridium difficile infection (CDI): Correlation of In Vitro Spectrum of Activity with Human Gut Microbiome Profiles from a Phase 2 Clinical Trial

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy209.159 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S67-S67

Author(s):

Richard Vickers ◽

Ellie J C Goldstein ◽

Diane Citron ◽

David Snydman ◽

Cheleste M Thorpe ◽

...

Keyword(s):

Clinical Trial ◽

Gut Microbiome ◽

Phase 2 ◽

Human Gut ◽

Human Gut Microbiome ◽

Moderate Growth ◽

Grant Recipient ◽

Phase 2 Clinical Trial ◽

Clostridium Spp

Abstract Background Recurrence of CDI (rCDI) is associated with perturbation of the gut microbiome during treatment with vancomycin (VAN) or metronidazole (MTZ). RDZ is a novel, targeted spectrum antibacterial under investigation to treat CDI and reduce rCDI. Here correlation of in vitro spectrum of activity with preservation of the human gut microbiome and clinical outcomes is presented. Methods Susceptibility testing was to CLSI standards with VAN, MTZ, and fidaxomicin (FDX) comparators. The Phase 2 clinical trial was a double-blind, randomized study of 100 patients assigned 1:1 to 10 days RDZ 200 mg BID or VAN 125 mg QID treatment. Primary endpoint was sustained clinical response (SCR), defined as cure at end of therapy (EOT), and no rCDI for the next 30 days. Relative effects of RDZ and VAN on the gut microbiome were examined by sequencing 16S rDNA amplicons from stool collected at baseline, days 5, 10, 25, and end of study. Bioinformatic analyses were performed in QIIME. Results RDZ C. difficile (N = 50) MIC range was 0.125–0.25 μg/mL. Clostridium spp. showed varied RDZ susceptibility; C. innocuum MIC90 1 μg/mL, C. ramosum and C. perfringens MIC90 >512 μg/mL. VAN showed potent to moderate growth inhibition of all Clostridium spp. (MIC range 1–16 µg/mL). Limited RDZ activity was observed for Gram-positive anaerobes, including Bifidobacteria, Eggerthella, Finegoldia, and Peptostreptococcus (MIC90 >512, >512, 64, and 64 μg/mL) compared with VAN (MIC90 1, 4, 0.5, and 0.5 μg/mL). Bacteroides fragilis MIC90 for RDZ and VAN were >512 and 64 µg/mL, respectively. These in vitro data correlate closely with human microbiome profiles. RDZ reduced C. difficile to below detection with other reductions in abundancy observed in only 2 families from the Clostridia. VAN at EOT resulted in significant losses, often below detection, in 4 Firmicutes families, Actinobacteria, and Bacteroidetes and a 25-fold increase in Proteobacteria abundance. The preservation of the microbiome by RDZ likely accounted for reduced rCDI compared with VAN with RDZ shown to be superior on SCR to VAN with rates of 66.7% and 42.4%, respectively (pre-specified 90% CI 3.1, 39.1). Conclusion These data demonstrate strong translation of in vitro spectrum to human gut microbiome preservation during therapy and support further clinical development of RDZ. Disclosures R. Vickers, Summit Therapeutics: Employee, Salary and Stock options. E. J. C. Goldstein, Summit Therapeutics: Grant Investigator and Scientific Advisor, Consulting fee and Grant recipient. D. Citron, Summit Therapeutics: Grant Investigator, Research grant. D. Snydman, Summit Therapeutics: Grant Investigator, Grant recipient. C. M. Thorpe, Summit Therapeutics: Grant Investigator and Scientific Advisor, Consulting fee and Grant recipient. A. V. Kane, Summit Therapeutics: Grant Investigator, Grant recipient.

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