scholarly journals Fine carbohydrate structure governs the structure and function of human gut microbiota independently of variation in glycosyl residue composition

2021 ◽  
Author(s):  
Arianna D. Romero Marcia ◽  
Tianming Yao ◽  
Ming-Hsu Chen ◽  
Renee E. Oles ◽  
Stephen R. Lindemann
Keyword(s):  
Community Structure ◽  
Gut Microbiota ◽  
Structure And Function ◽  
Carbohydrate Structure ◽  
Sugar Composition ◽  
Human Gut ◽  
And Function ◽  
The Impact ◽  
Residue Composition

AbstractIncreased dietary fiber consumption has been shown to increase human gut microbial diversity, but the mechanisms driving this effect remain unclear. One possible explanation is that microbes are able to divide metabolic labor in consumption of complex carbohydrates, which are composed of diverse glycosidic linkages that require specific cognate enzymes for degradation. However, as naturally derived fibers vary in both sugar composition and linkage structure, it is challenging to separate out the impact of each of these variables. We hypothesized that fine differences in carbohydrate linkage structure would govern microbial community structure and function independently of variation in glycosyl residue composition. To test this hypothesis, we fermented commercially available soluble resistant glucans, which are uniformly composed of glucose linked in different structural arrangements, in vitro with fecal inocula from each of three individuals. We measured metabolic outputs (pH, gas, and short-chain fatty acid production) and community structure via 16S rRNA amplicon sequencing. We determined that community metabolic outputs from identical glucans were highly individual, emerging from divergent initial microbiome structures. However, specific operational taxonomic units responded similarly in growth responses across individuals’ microbiota, though in context-dependent ways; these data suggested that certain taxa were more efficient in competing for some structures than others. Together, these data support the hypothesis that variation in linkage structure, independent of sugar composition, governs compositional and functional responses of microbiota.ImportancePrevious studies have reported how physical and chemical structures of carbohydrates influence the gut microbiota, however, variability across dietary fibers in monosaccharide composition and linkage structure obscures the relationship between fine polysaccharide linkage structure and microbial fitness. Revealing connections between subtle differences in glucan structure and microbial composition and metabolic responses, this study suggests much greater attention to substrate structure in the design of experiments to test fiber-microbiome responses in vitro and in vivo. Further, it underscores that, although microbiome responses to distinct fibers are individual and vary among specific glucans, similar carbohydrate structure-microbe relationships occur across individual donor communities. Together, these data may help explain why some individuals may respond (while others do not) to fiber treatments in human feeding trials and support the long-term goal of rational inclusion of specific fibers in dietary patterns to modulate the gut microbiome in support of health.

scholarly journals Fine Carbohydrate Structure of Dietary Resistant Glucans Governs the Structure and Function of Human Gut Microbiota

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2924
Author(s):  
Arianna D. Romero Marcia ◽  
Tianming Yao ◽  
Ming-Hsu Chen ◽  
Renee E. Oles ◽  
Stephen R. Lindemann
Keyword(s):  
Community Structure ◽  
Structure And Function ◽  
Growth Responses ◽  
Sugar Composition ◽  
Functional Responses ◽  
Human Gut ◽  
Fatty Acid Production ◽  
And Function ◽  
The Impact

Increased dietary fiber consumption has been shown to increase human gut microbial diversity, but the mechanisms driving this effect remain unclear. One possible explanation is that microbes are able to divide metabolic labor in consumption of complex carbohydrates, which are composed of diverse glycosidic linkages that require specific cognate enzymes for degradation. However, as naturally derived fibers vary in both sugar composition and linkage structure, it is challenging to separate out the impact of each of these variables. We hypothesized that fine differences in carbohydrate linkage structure would govern microbial community structure and function independently of variation in glycosyl residue composition. To test this hypothesis, we fermented commercially available soluble resistant glucans, which are uniformly composed of glucose linked in different structural arrangements, in vitro with fecal inocula from each of three individuals. We measured metabolic outputs (pH, gas, and short-chain fatty acid production) and community structure via 16S rRNA amplicon sequencing. We determined that community metabolic outputs from identical glucans were highly individual, emerging from divergent initial microbiome structures. However, specific operational taxonomic units (OTUs) responded similarly in growth responses across individuals’ microbiota, though in context-dependent ways; these data suggested that certain taxa were more efficient in competing for some structures than others. Together, these data support the hypothesis that variation in linkage structure, independent of sugar composition, governs compositional and functional responses of microbiota.

scholarly journals Multiplatform Physiologic and Metabolic Phenotyping Reveals Microbial Toxicity

mSystems ◽  
2018 ◽  
Vol 3 (6) ◽  
Author(s):  
Jingwei Cai ◽  
Robert G. Nichols ◽  
Imhoi Koo ◽  
Zachary A. Kalikow ◽  
Limin Zhang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Amino Acids ◽  
Flow Cytometry ◽  
Free Radical ◽  
Gut Microbiota ◽  
Structure And Function ◽  
Metabolic Phenotyping ◽  
And Function

ABSTRACTThe gut microbiota is susceptible to modulation by environmental stimuli and therefore can serve as a biological sensor. Recent evidence suggests that xenobiotics can disrupt the interaction between the microbiota and host. Here, we describe an approach that combinesin vitromicrobial incubation (isolated cecal contents from mice), flow cytometry, and mass spectrometry- and1H nuclear magnetic resonance (NMR)-based metabolomics to evaluate xenobiotic-induced microbial toxicity. Tempol, a stabilized free radical scavenger known to remodel the microbial community structure and functionin vivo, was studied to assess its direct effect on the gut microbiota. The microbiota was isolated from mouse cecum and was exposed to tempol for 4 h under strict anaerobic conditions. The flow cytometry data suggested that short-term tempol exposure to the microbiota is associated with disrupted membrane physiology as well as compromised metabolic activity. Mass spectrometry and NMR metabolomics revealed that tempol exposure significantly disrupted microbial metabolic activity, specifically indicated by changes in short-chain fatty acids, branched-chain amino acids, amino acids, nucleotides, glucose, and oligosaccharides. In addition, a mouse study with tempol (5 days gavage) showed similar microbial physiologic and metabolic changes, indicating that thein vitroapproach reflectedin vivoconditions. Our results, through evaluation of microbial viability, physiology, and metabolism and a comparison ofin vitroandin vivoexposures with tempol, suggest that physiologic and metabolic phenotyping can provide unique insight into gut microbiota toxicity.IMPORTANCEThe gut microbiota is modulated physiologically, compositionally, and metabolically by xenobiotics, potentially causing metabolic consequences to the host. We recently reported that tempol, a stabilized free radical nitroxide, can exert beneficial effects on the host through modulation of the microbiome community structure and function. Here, we investigated a multiplatform phenotyping approach that combines high-throughput global metabolomics with flow cytometry to evaluate the direct effect of tempol on the microbiota. This approach may be useful in deciphering how other xenobiotics directly influence the microbiota.

scholarly journals Carbohydrate complexity structures stable diversity in gut-derived microbial consortia under high dilution pressure

2020 ◽  
Author(s):  
Tianming Yao ◽  
Ming-Hsu Chen ◽  
Stephen R. Lindemann
Keyword(s):  
Microbial Diversity ◽  
Structural Complexity ◽  
Structure And Function ◽  
Microbial Consortia ◽  
Carbohydrate Structure ◽  
High Dilution ◽  
Chemical Complexity ◽  
Metabolic Interactions ◽  
And Function

ABSTRACTDietary fibers are major substrates for the colonic microbiota, but the structural specificity of these fibers for the diversity, structure, and function of gut microbial communities are poorly understood. Here, we employed an in vitro sequential batch fecal culture approach to determine: 1) whether the chemical complexity of a carbohydrate structure influences its ability to maintain microbial diversity in the face of high dilution pressure and 2) whether substrate structuring or obligate microbe-microbe metabolic interactions (e.g. exchange of amino acids or vitamins) exert more influence on maintained diversity. Sorghum arabinoxylan (SAX, complex polysaccharide), inulin (low-complexity oligosaccharide) and their corresponding monosaccharide controls were selected as model carbohydrates. Our results demonstrate that complex carbohydrates stably sustain diverse microbial consortia. Further, very similar final consortia were enriched on SAX from the same individual’s fecal microbiota across a one-month interval, suggesting that polysaccharide structure is more influential than stochastic alterations in microbiome composition in governing the outcomes of sequential batch cultivation experiments. SAX-consuming consortia were anchored by Bacteroides ovatus and retained diverse consortia of >12 OTUs; whereas final inulin-consuming consortia were dominated either by Klebsiella pneumoniae or Bifidobacterium sp. and Escherichia coli. Furthermore, auxotrophic interactions were less influential in structuring microbial consortia consuming SAX than the less-complex inulin. These data suggest that carbohydrate structural complexity affords independent niches that structure fermenting microbial consortia, whereas other metabolic interactions govern the composition of communities fermenting simpler carbohydrates.IMPORTANCEThe mechanisms by which gut microorganisms compete for and cooperate on human-indigestible carbohydrates of varying structural complexity remain unclear. Gaps in this understanding make it challenging to predict the effect of a particular dietary fiber’s structure on the diversity, composition, or function of gut microbiomes, especially with inter-individual variability in diets and microbiomes. Here, we demonstrate that carbohydrate structure governs the diversity of gut microbiota under high dilution pressure, suggesting that such structures may support microbial diversity in vivo. Further, we also demonstrate that carbohydrate polymers are not equivalent in the strength by which they influence community structure and function, and that metabolic interactions among members arising due to auxotrophy exert significant influence on the outcomes of these competitions for simpler polymers. Collectively, these data suggest that large, complex dietary fiber polysaccharides structure the human gut ecosystem in ways that smaller and simpler ones may not.

scholarly journals Regulation of phagolysosomal activity by miR-204 critically influences structure and function of retinal pigment epithelium/retina

2019 ◽  
Vol 28 (20) ◽  
pp. 3355-3368 ◽  
Author(s):  
Congxiao Zhang ◽  
Kiyoharu J Miyagishima ◽  
Lijin Dong ◽  
Aaron Rising ◽  
Malika Nimmagadda ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Primary Cultures ◽  
Structure And Function ◽  
Apical Surface ◽  
Altered Expression ◽  
And Function ◽  
The Impact

Abstract MicroRNA-204 (miR-204) is expressed in pulmonary, renal, mammary and eye tissue, and its reduction can result in multiple diseases including cancer. We first generated miR-204−/− mice to study the impact of miR-204 loss on retinal and retinal pigment epithelium (RPE) structure and function. The RPE is fundamentally important for maintaining the health and integrity of the retinal photoreceptors. miR-204−/− eyes evidenced areas of hyper-autofluorescence and defective photoreceptor digestion, along with increased microglia migration to the RPE. Migratory Iba1+ microglial cells were localized to the RPE apical surface where they participated in the phagocytosis of photoreceptor outer segments (POSs) and contributed to a persistent build-up of rhodopsin. These structural, molecular and cellular outcomes were accompanied by decreased light-evoked electrical responses from the retina and RPE. In parallel experiments, we suppressed miR-204 expression in primary cultures of human RPE using anti-miR-204. In vitro suppression of miR-204 in human RPE similarly showed abnormal POS clearance and altered expression of autophagy-related proteins and Rab22a, a regulator of endosome maturation. Together, these in vitro and in vivo experiments suggest that the normally high levels of miR-204 in RPE can mitigate disease onset by preventing generation of oxidative stress and inflammation originating from intracellular accumulation of undigested photoreactive POS lipids. More generally, these results implicate RPE miR-204-mediated regulation of autophagy and endolysosomal interaction as a critical determinant of normal RPE/retina structure and function.

scholarly journals Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine-N-Oxide

mBio ◽  
2015 ◽  
Vol 6 (2) ◽  
Author(s):  
Kymberleigh A. Romano ◽  
Eugenio I. Vivas ◽  
Daniel Amador-Noguez ◽  
Federico E. Rey
Keyword(s):  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
Human Life ◽  
Water Soluble ◽  
Human Gut ◽  
Choline Intake ◽  
Low Levels ◽  
And Function ◽  
Dietary Choline

ABSTRACT Choline is a water-soluble nutrient essential for human life. Gut microbial metabolism of choline results in the production of trimethylamine (TMA), which upon absorption by the host is converted in the liver to trimethylamine-N-oxide (TMAO). Recent studies revealed that TMAO exacerbates atherosclerosis in mice and positively correlates with the severity of this disease in humans. However, which microbes contribute to TMA production in the human gut, the extent to which host factors (e.g., genotype) and diet affect TMA production and colonization of these microbes, and the effects TMA-producing microbes have on the bioavailability of dietary choline remain largely unknown. We screened a collection of 79 sequenced human intestinal isolates encompassing the major phyla found in the human gut and identified nine strains capable of producing TMA from choline in vitro. Gnotobiotic mouse studies showed that TMAO accumulates in the serum of animals colonized with TMA-producing species, but not in the serum of animals colonized with intestinal isolates that do not generate TMA from choline in vitro. Remarkably, low levels of colonization by TMA-producing bacteria significantly reduced choline levels available to the host. This effect was more pronounced as the abundance of TMA-producing bacteria increased. Our findings provide a framework for designing strategies aimed at changing the representation or activity of TMA-producing bacteria in the human gut and suggest that the TMA-producing status of the gut microbiota should be considered when making recommendations about choline intake requirements for humans. IMPORTANCE Cardiovascular disease (CVD) is the leading cause of death and disability worldwide, and increased trimethylamine N-oxide (TMAO) levels have been causally linked with CVD development. This work identifies members of the human gut microbiota responsible for both the accumulation of trimethylamine (TMA), the precursor of the proatherogenic compound TMAO, and subsequent decreased choline bioavailability to the host. Understanding how to manipulate the representation and function of choline-consuming, TMA-producing species in the intestinal microbiota could potentially lead to novel means for preventing or treating atherosclerosis and choline deficiency-associated diseases.

scholarly journals Differential Effects of Antibiotic Therapy on the Structure and Function of Human Gut Microbiota

PLoS ONE ◽  
2013 ◽  
Vol 8 (11) ◽  
pp. e80201 ◽  
Author(s):  
Ana Elena Pérez-Cobas ◽  
Alejandro Artacho ◽  
Henrik Knecht ◽  
María Loreto Ferrús ◽  
Anette Friedrichs ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Antibiotic Therapy ◽  
Structure And Function ◽  
Human Gut ◽  
Differential Effects ◽  
Human Gut Microbiota ◽  
And Function

scholarly journals Long term exposure of human gut microbiota with high and low emulsifier sensitivity to soy lecithin in M-SHIME model.

2021 ◽  
Author(s):  
Lisa Miclotte ◽  
Ellen De Paepe ◽  
Qiqiong Li ◽  
Andreja Rajkovic ◽  
John Van Camp ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Day Treatment ◽  
Treatment Phase ◽  
Microbial Composition ◽  
Soy Lecithin ◽  
Potential Health ◽  
And Function ◽  
The Impact

In the context of the potential health hazards related to food processing, dietary emulsifiers have been shown to alter the structure and function of the gut microbial community, both in vivo and in vitro. In mouse models, these emulsifier exposed gut microbiota were shown to contribute to gut inflammation. Several knowledge gaps remain to be addressed though. As such, the impact from a longer timeframe of exposure on the gut microbiota is not known and interindividual variability in microbiome response needs to be measured. To answer these research questions, in this study the faecal microbiota from two individuals, previously selected for high and low emulsifier sensitivity, were exposed to two concentrations of soy lecithin during a 7 day treatment phase in the dynamic mucosal simulator of the human intestinal microbial ecosystem (M-SHIME). The results showed mild effects from soy lecithin on the composition and functionality of these microbial communities, which depended on the original microbial composition. The effects also mostly levelled off after 3 days of exposure. The emulsifier sensitivity for which the microbiota were selected, was preserved. Some potentially concerning effects were also registered: butyrate levels, positively correlating with Faecalibacterium abundance, were lowered by soy lecithin. Also the abundance of the beneficial Bifidobacterium genus was lowered, while the abundance of the notorious unclassified Enterobacteriaceae was increased. Within the family of the unclassified Lachnospiraceae, several genera were either suppressed or stimulated. The effects that these microbial alterations would have on a living host is not yet certain, especially given the fact that large fractions of soy lecithins constituents can be absorbed. Nevertheless, choline and phosphatidylcholine, both primary and absorbable constituents of soy lecithin, have recently been linked to cardiovascular disease via the generation of TMA by the gut microbiota. Further studies that validate our findings and link them to potential health outcomes are thus justified.

scholarly journals Novel approaches for analysing gut microbes and dietary polyphenols: challenges and opportunities

Microbiology ◽  
2010 ◽  
Vol 156 (11) ◽  
pp. 3224-3231 ◽  
Author(s):  
R. A. Kemperman ◽  
S. Bolca ◽  
L. C. Roger ◽  
E. E. Vaughan
Keyword(s):  
Gut Microbiota ◽  
Health Effects ◽  
Fruit And Vegetables ◽  
Human Gut ◽  
Microbial Composition ◽  
Dietary Polyphenols ◽  
Host Health ◽  
The Impact

Polyphenols, ubiquitously present in the food we consume, may modify the gut microbial composition and/or activity, and moreover, may be converted by the colonic microbiota to bioactive compounds that influence host health. The polyphenol content of fruit and vegetables and derived products is implicated in some of the health benefits bestowed on eating fruit and vegetables. Elucidating the mechanisms behind polyphenol metabolism is an important step in understanding their health effects. Yet, this is no trivial assignment due to the diversity encountered in both polyphenols and the gut microbial composition, which is further confounded by the interactions with the host. Only a limited number of studies have investigated the impact of dietary polyphenols on the complex human gut microbiota and these were mainly focused on single polyphenol molecules and selected bacterial populations. Our knowledge of gut microbial genes and pathways for polyphenol bioconversion and interactions is poor. Application of specific in vitro or in vivo models mimicking the human gut environment is required to analyse these diverse interactions. A particular benefit can now be gained from next-generation analytical tools such as metagenomics and metatranscriptomics allowing a wider, more holistic approach to the analysis of polyphenol metabolism. Understanding the polyphenol–gut microbiota interactions and gut microbial bioconversion capacity will facilitate studies on bioavailability of polyphenols in the host, provide more insight into the health effects of polyphenols and potentially open avenues for modulation of polyphenol bioactivity for host health.

scholarly journals Farnesoid X Receptor Signaling Shapes the Gut Microbiota and Controls Hepatic Lipid Metabolism

mSystems ◽  
2016 ◽  
Vol 1 (5) ◽  
Author(s):  
Limin Zhang ◽  
Cen Xie ◽  
Robert G. Nichols ◽  
Siu H. J. Chan ◽  
Changtao Jiang ◽  
...  
Keyword(s):  
Community Structure ◽  
Gut Microbiota ◽  
Bile Salt ◽  
Structure And Function ◽  
Farnesoid X Receptor ◽  
Bile Salt Hydrolase ◽  
Metabolic Models ◽  
And Function ◽  
Genome Scale ◽  
Bile Salt Hydrolase Activity

ABSTRACT The farnesoid X receptor (FXR) plays an important role in mediating the dialog between the host and gut microbiota, particularly through modulation of enterohepatic circulation of bile acids. Mounting evidence suggests that genetic ablation of Fxr in the gut or gut-restricted chemical antagonism of the FXR promotes beneficial health effects, including the prevention of nonalcoholic fatty liver disease in rodent models. However, questions remain unanswered, including whether modulation of FXR activity plays a role in shaping the gut microbiota community structure and function and what metabolic pathways of the gut microbiota contribute in an FXR-dependent manner to the host phenotype. In this report, new insights are gained into the metabolic contribution of the gut microbiota to the metabolic phenotypes, including establishing a link between FXR antagonism, bacterial bile salt hydrolase activity, and fermentation. Multiple approaches, including unique mouse models as well as metabolomics and genome-scale metabolic models, were employed to confirm these results. The gut microbiota modulates obesity and associated metabolic phenotypes in part through intestinal farnesoid X receptor (FXR) signaling. Glycine-β-muricholic acid (Gly-MCA), an intestinal FXR antagonist, has been reported to prevent or reverse high-fat diet (HFD)-induced and genetic obesity, insulin resistance, and fatty liver; however, the mechanism by which these phenotypes are improved is not fully understood. The current study investigated the influence of FXR activity on the gut microbiota community structure and function and its impact on hepatic lipid metabolism. Predictions about the metabolic contribution of the gut microbiota to the host were made using 16S rRNA-based PICRUSt (phylogenetic investigation of communities by reconstruction of unobserved states), then validated using 1H nuclear magnetic resonance-based metabolomics, and results were summarized by using genome-scale metabolic models. Oral Gly-MCA administration altered the gut microbial community structure, notably reducing the ratio of Firmicutes to Bacteroidetes and its PICRUSt-predicted metabolic function, including reduced production of short-chain fatty acids (substrates for hepatic gluconeogenesis and de novo lipogenesis) in the ceca of HFD-fed mice. Metabolic improvement was intestinal FXR dependent, as revealed by the lack of changes in HFD-fed intestine-specific Fxr-null (Fxr ΔIE) mice treated with Gly-MCA. Integrative analyses based on genome-scale metabolic models demonstrated an important link between Lactobacillus and Clostridia bile salt hydrolase activity and bacterial fermentation. Hepatic metabolite levels after Gly-MCA treatment correlated with altered levels of gut bacterial species. In conclusion, modulation of the gut microbiota by inhibition of intestinal FXR signaling alters host liver lipid metabolism and improves obesity-related metabolic dysfunction. IMPORTANCE The farnesoid X receptor (FXR) plays an important role in mediating the dialog between the host and gut microbiota, particularly through modulation of enterohepatic circulation of bile acids. Mounting evidence suggests that genetic ablation of Fxr in the gut or gut-restricted chemical antagonism of the FXR promotes beneficial health effects, including the prevention of nonalcoholic fatty liver disease in rodent models. However, questions remain unanswered, including whether modulation of FXR activity plays a role in shaping the gut microbiota community structure and function and what metabolic pathways of the gut microbiota contribute in an FXR-dependent manner to the host phenotype. In this report, new insights are gained into the metabolic contribution of the gut microbiota to the metabolic phenotypes, including establishing a link between FXR antagonism, bacterial bile salt hydrolase activity, and fermentation. Multiple approaches, including unique mouse models as well as metabolomics and genome-scale metabolic models, were employed to confirm these results.

scholarly journals The Effect of Perfluorooctane Sulfonate, Exposure Time, and Chemical Mixtures on Methanogenic Community Structure and Function

2015 ◽  
Vol 8s2 ◽  
pp. MBI.S31345 ◽  
Author(s):  
Patrick J. McNamara ◽  
Timothy M. LaPara ◽  
Paige J. Novak
Keyword(s):  
Community Structure ◽  
Exposure Time ◽  
Methane Production ◽  
Perfluorooctane Sulfonate ◽  
Structure And Function ◽  
Short Term ◽  
Anaerobic Digesters ◽  
And Function ◽  
The Impact

A plethora of organic micropollutant mixtures are found in untreated municipal wastewater. Anaerobic digesters receive large loadings of hydrophobic micropollutants that sorb to wastewater biosolids. Despite micropollutants being pervasive as mixtures, little research is available to explain the impact that mixtures of compounds, as well as exposure time, have on microbial communities in anaerobic digesters. Perfluorooctane sulfonate (PFOS) was added to anaerobic enrichment cultures in both short-term (14 days) and long-term (140 days) studies to determine the impact of exposure time. Additionally, triclosan was added during the experiments to investigate the impact of mixtures on community structure and function. PFOS did not alter methane production in short-term studies, but in long-term studies, methane production increased, consistent with our hypothesis that PFOS may act as a metabolic uncoupler. The impact of triclosan on methane production was exacerbated when PFOS was already present in the anaerobic enrichment cultures. Triclosan also had greater impacts on microbial community structures in the bottles that had been exposed to PFOS long-term. These results demonstrate that both chemical mixtures and exposure time are important parameters to address when trying to define the impacts of micropollutants on anaerobic microbial communities.

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