Functional heterogeneity in the fermentation capabilities of the healthy human gut microbiota

AbstractThe human gut microbiota is known for its highly heterogeneous composition across different individuals. However, relatively little is known about functional differences in its ability to ferment complex polysaccharides. Through ex vivo measurements from healthy human donors, we show that individuals vary markedly in their microbial metabolic phenotypes (MMPs), mirroring differences in their microbiota composition, and resulting in the production of different quantities and proportions of Short Chain Fatty Acids (SCFAs) from the same inputs. We also show that aspects of these MMPs can be predicted from composition using 16S rRNA sequencing. From experiments performed using the same dietary fibers in vivo, we demonstrate that an ingested bolus of fiber is almost entirely consumed by the microbiota upon passage. We leverage our ex vivo data to construct a model of SCFA production and absorption in vivo, and argue that inter-individual differences in quantities of absorbed SCFA are directly related to differences in production. Taken together, these data suggest that personalized dietary fiber supplementation based on an individual’s MMP is an attractive therapeutic strategy for treating diseases associated with SCFA production.

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Functional heterogeneity in the fermentation capabilities of the healthy human gut microbiota

PLoS ONE ◽

10.1371/journal.pone.0254004 ◽

2021 ◽

Vol 16 (7) ◽

pp. e0254004

Author(s):

Thomas Gurry ◽

Le Thanh Tu Nguyen ◽

Xiaoqian Yu ◽

Eric J. Alm

Keyword(s):

Gut Microbiota ◽

Ex Vivo ◽

Short Chain Fatty Acids ◽

Human Gut ◽

Healthy Human ◽

Human Gut Microbiota ◽

Functional Differences ◽

Rrna Sequencing ◽

Quantitative Understanding

The human gut microbiota is known for its highly heterogeneous composition across different individuals. However, relatively little is known about functional differences in its ability to ferment complex polysaccharides. Through ex vivo measurements from healthy human donors, we show that individuals vary markedly in their microbial metabolic phenotypes (MMPs), mirroring differences in their microbiota composition, and resulting in the production of different quantities and proportions of Short Chain Fatty Acids (SCFAs) from the same inputs. We also show that aspects of these MMPs can be predicted from composition using 16S rRNA sequencing. From experiments performed using the same dietary fibers in vivo, we demonstrate that an ingested bolus of fiber is almost entirely consumed by the microbiota upon passage. We leverage our ex vivo data to construct a model of SCFA production and absorption in vivo, and argue that inter-individual differences in quantities of absorbed SCFA are directly related to differences in production. Though in vivo studies are required to confirm these data in the context of the gut, in addition to in vivo read outs of SCFAs produced in response to specific fiber spike-ins, these data suggest that optimizing SCFA production in a given individual through targeted fiber supplementation requires quantitative understanding of their MMP.

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Prebiotics and Community Composition Influence Gas Production of the Human Gut Microbiota

mBio ◽

10.1128/mbio.00217-20 ◽

2020 ◽

Vol 11 (5) ◽

Author(s):

Xiaoqian Yu ◽

Thomas Gurry ◽

Le Thanh Tu Nguyen ◽

Hunter S. Richardson ◽

Eric J. Alm

Keyword(s):

Fatty Acids ◽

Chemical Composition ◽

Gut Microbiota ◽

Community Composition ◽

Human Body ◽

Ex Vivo ◽

Short Chain Fatty Acids ◽

Gas Production ◽

Human Gut ◽

Human Gut Microbiota

ABSTRACT Prebiotics confer benefits to human health, often by promoting the growth of gut bacteria that produce metabolites valuable to the human body, such as short-chain fatty acids (SCFAs). While prebiotic selection has strongly focused on maximizing the production of SCFAs, less attention has been paid to gases, a by-product of SCFA production that also has physiological effects on the human body. Here, we investigate how the content and volume of gas production by human gut microbiota are affected by the chemical composition of the prebiotic and the community composition of the microbiota. We first constructed a linear system model based on mass and electron balance and compared the theoretical product ranges of two prebiotics, inulin and pectin. Modeling shows that pectin is more restricted in product space, with less potential for H2 but more potential for CO2 production. An ex vivo experimental system showed pectin degradation produced significantly less H2 than inulin, but CO2 production fell outside the theoretical product range, suggesting fermentation of fecal debris. Microbial community composition also impacted results: methane production was dependent on the presence of Methanobacteria, while interindividual differences in H2 production during inulin degradation were driven by a Lachnospiraceae taxon. Overall, these results suggest that both the chemistry of the prebiotic and the composition of the microbiota are relevant to gas production. Metabolic processes that are relatively prevalent in the microbiome, such as H2 production, will depend more on substrate, while rare metabolisms such as methanogenesis depend more strongly on microbiome composition. IMPORTANCE Prebiotic fermentation in the gut often leads to the coproduction of short-chain fatty acids (SCFAs) and gases. While excess gas production can be a potential problem for those with functional gut disorders, gas production is rarely considered during prebiotic design. In this study, we combined the use of theoretical models and an ex vivo experimental platform to illustrate that both the chemical composition of the prebiotic and the community composition of the human gut microbiota can affect the volume and content of gas production during prebiotic fermentation. Specifically, more prevalent metabolic processes such as hydrogen production were strongly affected by the oxidation state of the probiotic, while rare metabolisms such as methane production were less affected by the chemical nature of the substrate and entirely dependent on the presence of Methanobacteria in the microbiota.

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Prebiotics and community composition influence gas production of the human gut microbiota

10.1101/2020.01.30.928085 ◽

2020 ◽

Author(s):

Xiaoqian Yu ◽

Thomas Gurry ◽

Le Thanh Tu Nguyen ◽

Hunter S. Richardson ◽

Eric J. Alm

Keyword(s):

Fatty Acids ◽

Chemical Composition ◽

Gut Microbiota ◽

Community Composition ◽

Human Body ◽

Ex Vivo ◽

Short Chain Fatty Acids ◽

Gas Production ◽

Human Gut ◽

Human Gut Microbiota

AbstractPrebiotics confer benefits to human health often by promoting the growth of gut bacteria that produce metabolites valuable to the human body, such as short chain fatty acids (SCFAs). While prebiotic selection has strongly focused on maximizing the production of SCFAs, less attention has been paid to gases, a byproduct of SCFA production that also has physiological effects on the human body. Here, we investigate how the content and volume of gas production by human gut microbiota is affected by the chemical composition of the prebiotic and by the composition of the microbiota. We first constructed a linear systems model based on mass and electron balance and compared the theoretical product range of two prebiotics, inulin and pectin. Modeling shows that pectin is more restricted in product space, with less potential for H2 but more potential for CO2 production. An ex vivo experimental system showed pectin degradation produced significantly less H2 than inulin, but CO2 production fell outside the theoretical product range, suggesting fermentation of fecal debris. Microbial community composition also impacted results: methane production was dependent on the presence of Methanobacteria, while inter-individual differences in H2 production during inulin degradation was driven by a Lachnospiraceae taxon. Overall, these results suggest that both the chemistry of the prebiotic and the composition of the microbiota are relevant to gas production. Metabolic processes that are relatively prevalent in the microbiome, such as H2 production will depend more on substrate, while rare metabolisms like methanogenesis depend more strongly on microbiome composition.ImportancePrebiotic fermentation in the gut often leads to the co-production of short chain fatty acids (SCFAs) and gases. While excess gas production can be a potential problem for those with functional gut disorders, gas production is rarely taken into account during prebiotic design. In this study, we combined the use of theoretical models and an ex vivo experimental platform to illustrate that both the chemical composition of the prebiotic and the community composition of the human gut microbiota can affect the volume and content of gas production during prebiotic fermentation. Specifically, more prevalent metabolic processes such as hydrogen production was strongly affected by the oxidation state of the probiotic, while rare metabolisms such as methane production was less affected by the chemical nature of the substrate and entirely dependent on the presence of Methanobacteria in the microbiota.

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A Putative Type V Pilus Contributes toBacteroides thetaiotaomicronBiofilm Formation Capacity

Journal of Bacteriology ◽

10.1128/jb.00650-18 ◽

2019 ◽

Vol 201 (18) ◽

Cited By ~ 3

Author(s):

Jovana Mihajlovic ◽

Nathalie Bechon ◽

Christa Ivanova ◽

Florian Chain ◽

Alexandre Almeida ◽

...

Keyword(s):

Gut Microbiota ◽

Selection Procedure ◽

Bacteroides Thetaiotaomicron ◽

Human Gut ◽

Healthy Human ◽

Content Type ◽

Human Gut Microbiota ◽

Type V

ABSTRACTBacteroides thetaiotaomicronis a prominent anaerobic member of the healthy human gut microbiota. While the majority of functional studies onB. thetaiotaomicronaddressed its impact on the immune system and the utilization of diet polysaccharides,B. thetaiotaomicronbiofilm capacity and its contribution to intestinal colonization are still poorly characterized. We tested the natural adhesion of 34B. thetaiotaomicronisolates and showed that although biofilm capacity is widespread amongB. thetaiotaomicronstrains, this phenotype is masked or repressed in the widely used reference strain VPI 5482. Using transposon mutagenesis followed by a biofilm positive-selection procedure, we identified VPI 5482 mutants with increased biofilm capacity corresponding to an alteration in the C-terminal region of BT3147, encoded by theBT3148-BT3147locus, which displays homology with Mfa-like type V pili found in manyBacteroidetes. We show that BT3147 is exposed on theB. thetaiotaomicronsurface and that BT3147-dependent adhesion also requires BT3148, suggesting that BT3148 and BT3147 correspond to the anchor and stalk subunits of a new type V pilus involved inB. thetaiotaomicronadhesion. This study therefore introducesB. thetaiotaomicronas a model to study proteinaceous adhesins and biofilm-related phenotypes in this important intestinal symbiont.IMPORTANCEAlthough the gut anaerobeBacteroides thetaiotaomicronis a prominent member of the healthy human gut microbiota, little is known about its capacity to adhere to surfaces and form biofilms. Here, we identify that alteration of a surface-exposed protein corresponding to a type of pili found in manyBacteroidetesincreasesB. thetaiotaomicronbiofilm formation. This study lays the ground for establishing this bacterium as a model organism forin vitroandin vivostudies of biofilm-related phenotypes in gut anaerobes.

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Chemo-Preventive Potential of Falcarindiol-Enriched Fraction from Oplopanax elatus on Colorectal Cancer Interfered by Human Gut Microbiota

The American Journal of Chinese Medicine ◽

10.1142/s0192415x1950071x ◽

2019 ◽

Vol 47 (06) ◽

pp. 1381-1404 ◽

Cited By ~ 1

Author(s):

Jin Wang ◽

Li Shao ◽

Tai Rao ◽

Wei Zhang ◽

Wei-Hua Huang

Keyword(s):

Gut Microbiota ◽

Caspase 3 ◽

Human Gut ◽

Antiproliferative Effects ◽

Human Gut Microbiota ◽

Hct 116 ◽

Oplopanax Elatus ◽

Induced Apoptosis ◽

Ht 29

Oplopanax elatus (Nakai) Nakai is an oriental herb, the polyyne-enriched fraction of which (PEFO) showed anticolorectal cancer (anti-CRC) effects. Other concomitant components, which are inevitably bio-transformed by gut microbiota after oral administration, might be interfere with the pharmacodynamics of polyynes. However, the influence of human gut microbiota on molecules from O. elatus possessing anticancer activity are yet unknown. In this study, the compounds in PEFO and PEFO incubated with human gut microbiota were analyzed and tentatively identified by HPLC-DAD-QTOF-MS. Two main polyynes ((3[Formula: see text]8[Formula: see text]-falcarindiol and oplopandiol) were not significantly decomposed, but some new unknown molecules were discovered during incubation. However, the antiproliferative effects of PEFO incubated with human gut microbiota for 72 h (PEFO I) were much lower than that of PEFO on HCT-116, SW-480, and HT-29 cells. Furthermore, PEFO possessed better anti-CRC activity in vivo, and significantly induced apoptosis of the CRC cells, which was associated with activation of caspase-3 according to the Western-blot results ([Formula: see text]). These results suggest anticolorectal cancer activity of polyynes might be antagonized by some bio-converted metabolites after incubation with human gut microbiota. Therefore, it might be better for CRC prevention if the polyynes could be orally administrated as purified compounds.

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In vivo and in vitro metabolism of trans-resveratrol by human gut microbiota

American Journal of Clinical Nutrition ◽

10.3945/ajcn.112.049379 ◽

2013 ◽

Vol 97 (2) ◽

pp. 295-309 ◽

Cited By ~ 171

Author(s):

Lisa M Bode ◽

Diana Bunzel ◽

Melanie Huch ◽

Gyu-Sung Cho ◽

Denise Ruhland ◽

...

Keyword(s):

Gut Microbiota ◽

In Vitro Metabolism ◽

Human Gut ◽

Human Gut Microbiota

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Positive Synergistic Effects of Quercetin and Rice Bran on Human Gut Microbiota Reduces Enterobacteriaceae Family Abundance and Elevates Propionate in a Bioreactor Model

Frontiers in Microbiology ◽

10.3389/fmicb.2021.751225 ◽

2021 ◽

Vol 12 ◽

Author(s):

Sudeep Ghimire ◽

Supapit Wongkuna ◽

Ranjini Sankaranarayanan ◽

Elizabeth P. Ryan ◽

G. Jayarama Bhat ◽

...

Keyword(s):

Gut Microbiota ◽

Rice Bran ◽

Synergistic Effects ◽

Bacterial Species ◽

Positive Influence ◽

Human Gut ◽

Fatty Acid Production ◽

Microbiome Composition ◽

Human Gut Microbiota

Dietary fiber and flavonoids have substantial influence on the human gut microbiota composition that significantly impact health. Recent studies with dietary supplements such as quercetin and rice bran have shown beneficial impacts on the host alongside a positive influence of the gut microbiota. The specific bacterial species impacted by quercetin or rice bran in the diet is not well understood. In this study, we used a minibioreactor array system as a model to determine the effect of quercetin and rice bran individually, as well as in combination, on gut microbiota without the confounding host factors. We found that rice bran exerts higher shift in gut microbiome composition when compared to quercetin. At the species level, Acidaminococcus intestini was the only significantly enriched taxa when quercetin was supplemented, while 15 species were enriched in rice bran supplementation and 13 were enriched when quercetin and rice bran were supplemented in combination. When comparing the short chain fatty acid production, quercetin supplementation increased isobutyrate production while propionate dominated the quercetin and rice bran combined group. Higher levels of propionate were highly correlated to the lower abundance of the potentially pathogenic Enterobacteriaceae family. These findings suggest that the combination of quercetin and rice bran serve to enrich beneficial bacteria and reduce potential opportunistic pathogens. In vivo studies are necessary to determine how this synergy of quercetin and rice bran on microbiota impact host health.

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Enrichment of Food With Tannin Extracts Promotes Healthy Changes in the Human Gut Microbiota

Frontiers in Microbiology ◽

10.3389/fmicb.2021.625782 ◽

2021 ◽

Vol 12 ◽

Author(s):

Silvia Molino ◽

Alberto Lerma-Aguilera ◽

Nuria Jiménez-Hernández ◽

María José Gosalbes ◽

José Ángel Rufián-Henares ◽

...

Keyword(s):

Gut Microbiota ◽

Short Chain Fatty Acids ◽

Human Gut ◽

Human Gut Microbiota ◽

Wood Extracts ◽

Potential Benefits ◽

Next Generation Sequencing Ngs ◽

Generation Sequencing ◽

Booster Effect

Food and food bioactive components are major drivers of modulation of the human gut microbiota. Tannin extracts consist of a mix of bioactive compounds, which are already exploited in the food industry for their chemical and sensorial properties. The aim of our study was to explore the viability of associations between tannin wood extracts of different origin and food as gut microbiota modulators. 16S rRNA amplicon next-generation sequencing (NGS) was used to test the effects on the gut microbiota of tannin extracts from quebracho, chestnut, and tara associated with commercial food products with different composition in macronutrients. The different tannin-enriched and non-enriched foods were submitted to in vitro digestion and fermentation by the gut microbiota of healthy subjects. The profile of the short chain fatty acids (SCFAs) produced by the microbiota was also investigated. The presence of tannin extracts in food promoted an increase of the relative abundance of the genus Akkermansia, recognized as a marker of a healthy gut, and of various members of the Lachnospiraceae and Ruminococcaceae families, involved in SCFA production. The enrichment of foods with tannin extracts had a booster effect on the production of SCFAs, without altering the profile given by the foods alone. These preliminary results suggest a positive modulation of the gut microbiota with potential benefits for human health through the enrichment of foods with tannin extracts.

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