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Journal of Genetics and Genomics = Yi... Sep 2021Carrageenans (CGNs) are widely used in foods and pharmaceuticals although their safety remains controversial. To investigate the effects of CGNs and CGN-degrading...
Carrageenans (CGNs) are widely used in foods and pharmaceuticals although their safety remains controversial. To investigate the effects of CGNs and CGN-degrading bacteria in the human colon, we screened for CGN degradation by human fecal microbiota, and for inflammatory response to CGNs and/or CGN-degrading bacteria in germ free mice. Thin-layer chromatography indicated that high molecular weight (MW) CGNs (≥100 kDa) remained undegraded in the presence of human fecal microbiota, whereas low MW CGNs, i.e., κ-carrageenan oligosaccharides (KCO, ~4.5 kDa) were degraded when exposed to seven of eight human fecal samples, although sulfate groups were not removed during degradation. Bacteroides xylanisolvens and Escherichia coli isolates from fecal samples apparently degraded KCO synergistically, with B. xylanisolvens serving as the primary degrader. Combined treatment of KCO with KCO-degrading bacteria led to greater pro-inflammatory effects in the colon and rectum of germ-free mice than either KCO or bacteria alone. Similarly, p-p38-, CD3-, and CD79a-positive immune cells were more abundant in combined treatment group mice than in either single treatment group. Our study shows that KCO-degrading bacteria and the low MW products of KCO can promote proinflammatory effects in mice, and represent two key markers for evaluating CGN safety in foods or medicines.
Topics: Carrageenan
PubMed: 34400364
DOI: 10.1016/j.jgg.2021.08.001 -
MSystems Feb 2022Symbiotic bacteria are responsible for the majority of complex carbohydrate digestion in the human colon. Since the identities and amounts of dietary polysaccharides...
Symbiotic bacteria are responsible for the majority of complex carbohydrate digestion in the human colon. Since the identities and amounts of dietary polysaccharides directly impact the gut microbiota, determining which microorganisms consume specific nutrients is central for defining the relationship between diet and gut microbial ecology. Using a custom phenotyping array, we determined carbohydrate utilization profiles for 354 members of the , a dominant saccharolytic phylum. There was wide variation in the numbers and types of substrates degraded by individual bacteria, but phenotype-based clustering grouped members of the same species indicating that each species performs characteristic roles. The ability to utilize dietary polysaccharides and endogenous mucin glycans was negatively correlated, suggesting exclusion between these niches. By analyzing related Bacteroides ovatusBacteroides xylanisolvens strains that vary in their ability to utilize mucin glycans, we addressed whether gene clusters that confer this complex, multilocus trait are being gained or lost in individual strains. Pangenome reconstruction of these strains revealed a remarkably mosaic architecture in which genes involved in polysaccharide metabolism are highly variable and bioinformatics data provide evidence of interspecies gene transfer that might explain this genomic heterogeneity. Global transcriptomic analyses suggest that the ability to utilize mucin has been lost in some lineages of and , which harbor residual gene clusters that are involved in mucin utilization by strains that still actively express this phenotype. Our data provide insight into the breadth and complexity of carbohydrate metabolism in the microbiome and the underlying genomic events that shape these behaviors. Nonharmful bacteria are the primary microbial symbionts that inhabit the human gastrointestinal tract. These bacteria play many beneficial roles and in some cases can modify disease states, making it important to understand which nutrients sustain specific lineages. This knowledge will in turn lead to strategies to intentionally manipulate the gut microbial ecosystem. We designed a scalable, high-throughput platform for measuring the ability of gut bacteria to utilize polysaccharides, of which many are derived from dietary fiber sources that can be manipulated easily. Our results provide paths to expand phenotypic surveys of more diverse gut bacteria to understand their functions and also to leverage dietary fibers to alter the physiology of the gut microbial community.
Topics: Humans; Polysaccharides; Bacteria; Dietary Carbohydrates; Microbiota; Dietary Fiber; Genomics; Mucins
PubMed: 35166563
DOI: 10.1128/msystems.00947-21 -
Frontiers in Cellular and Infection... 2023The wide application of immune checkpoint inhibitors has significantly improved the survival expectation of cancer patients. While immunotherapy brings benefits to...
INTRODUCTION
The wide application of immune checkpoint inhibitors has significantly improved the survival expectation of cancer patients. While immunotherapy brings benefits to patients, it also results in a series of immune-related adverse events (irAEs). Increasing evidence suggests that the gut microbiome is critical for immunotherapy response and the development of irAEs.
METHODS
In this prospective study, we recruited 95 patients with advanced/unresectable gastrointestinal cancers treated with immunotherapy and report a comprehensive analysis of the association of the gut microbiome with irAEs. Metagenome sequencing was used to analyze the differences in bacterial composition and metabolic pathways of baseline fecal samples.
RESULTS
In summary, we identified bacterial species and metabolic pathways that might be associated with the occurrence of irAEs in gastric, esophageal, and colon cancers. Ruminococcus callidus and Bacteroides xylanisolvens were enriched in patients without severe irAEs. Several microbial metabolic pathways involved in the urea cycle, including citrulline and arginine biosynthesis, were associated with irAEs. We also found that irAEs in different cancer types and toxicity in specific organs and the endocrine system were associated with different gut microbiota profiles. These findings provide the basis for future mechanistic exploration.
Topics: Humans; Immune Checkpoint Inhibitors; Gastrointestinal Microbiome; Prospective Studies; Neoplasms; Gastrointestinal Neoplasms; Colonic Neoplasms; Immunotherapy
PubMed: 37051296
DOI: 10.3389/fcimb.2023.1099063 -
Frontiers in Microbiology 2017Novel microbes are either newly isolated genera and species from natural sources or bacterial strains derived from existing bacteria. Novel microbes are gaining... (Review)
Review
Novel microbes are either newly isolated genera and species from natural sources or bacterial strains derived from existing bacteria. Novel microbes are gaining increasing attention for the general aims to preserve and modify foods and to modulate gut microbiota. The use of novel microbes to improve health outcomes is of particular interest because growing evidence points to the importance of gut microbiota in human health. As well, some recently isolated microorganisms have promise for use as probiotics, although in-depth assessment of their safety is necessary. Recent examples of microorganisms calling for more detailed evaluation include , fructophilic lactic acid bacteria (FLAB), and . This paper discusses each candidate's safety evaluation for novel food or novel food ingredient approval according to European Union (EU) regulations. The factors evaluated include their beneficial properties, antibiotic resistance profiling, history of safe use (if available), publication of the genomic sequence, toxicological studies in agreement with novel food regulations, and the qualified presumptions of safety. Sufficient evidences have made possible to support and authorize the use of heat-inactivated in the European Union. In the case of , the discussion focuses on earlier safety studies and the strain's suitability. FLAB are also subjected to standard safety assessments, which, along with their proximity to lactic acid bacteria generally considered to be safe, may lead to novel food authorization in the future. Further research with will increase knowledge about its safety and probiotic properties and may lead to its future use as novel food. Upcoming changes in EUU Regulation 2015/2283 on novel food will facilitate the authorization of future novel products and might increase the presence of novel microbes in the food market.
PubMed: 28955311
DOI: 10.3389/fmicb.2017.01725 -
BMC Genomics May 2016Plant cell wall (PCW) polysaccharides and especially xylans constitute an important part of human diet. Xylans are not degraded by human digestive enzymes in the upper...
BACKGROUND
Plant cell wall (PCW) polysaccharides and especially xylans constitute an important part of human diet. Xylans are not degraded by human digestive enzymes in the upper digestive tract and therefore reach the colon where they are subjected to extensive degradation by some members of the symbiotic microbiota. Xylanolytic bacteria are the first degraders of these complex polysaccharides and they release breakdown products that can have beneficial effects on human health. In order to understand better how these bacteria metabolize xylans in the colon, this study was undertaken to investigate xylan breakdown by the prominent human gut symbiont Bacteroides xylanisolvens XB1A(T).
RESULTS
Transcriptomic analyses of B. xylanisolvens XB1A(T) grown on insoluble oat-spelt xylan (OSX) at mid- and late-log phases highlighted genes in a polysaccharide utilization locus (PUL), hereafter called PUL 43, and genes in a fragmentary remnant of another PUL, hereafter referred to as rPUL 70, which were highly overexpressed on OSX relative to glucose. Proteomic analyses supported the up-regulation of several genes belonging to PUL 43 and showed the important over-production of a CBM4-containing GH10 endo-xylanase. We also show that PUL 43 is organized in two operons and that the knockout of the PUL 43 sensor/regulator HTCS gene blocked the growth of the mutant on insoluble OSX and soluble wheat arabinoxylan (WAX). The mutation not only repressed gene expression in the PUL 43 operons but also repressed gene expression in rPUL 70.
CONCLUSION
This study shows that xylan degradation by B. xylanisolvens XB1A(T) is orchestrated by one PUL and one PUL remnant that are linked at the transcriptional level. Coupled to studies on other xylanolytic Bacteroides species, our data emphasize the importance of one peculiar CBM4-containing GH10 endo-xylanase in xylan breakdown and that this modular enzyme may be used as a functional marker of xylan degradation in the human gut. Our results also suggest that B. xylanisolvens XB1A(T) has specialized in the degradation of xylans of low complexity. This functional feature may provide a niche to all xylanolytic bacteria harboring similar PULs. Further functional and ecological studies on fibrolytic Bacteroides species are needed to better understand their role in dietary fiber degradation and their impact on intestinal health.
Topics: Bacterial Proteins; Bacteroides; Gastrointestinal Tract; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Humans; Multigene Family; Operon; Plant Proteins; Proteomics; Sequence Analysis, RNA; Xylans
PubMed: 27142817
DOI: 10.1186/s12864-016-2680-8 -
BioRxiv : the Preprint Server For... Oct 2023Bacterial strains evolve in response to the gut environment of their hosts, with genomic changes that influence their interactions with hosts as well as with other...
Bacterial strains evolve in response to the gut environment of their hosts, with genomic changes that influence their interactions with hosts as well as with other members of the gut community. Great apes in captivity have acquired strains of , which are common within gut microbiome of humans but not typically found other apes, thereby enabling characterization of strain evolution following colonization. Here, we isolate, sequence and reconstruct the history of gene gain and loss events in numerous captive-ape-associated strains since their divergence from their closest human-associated strains. We show that multiple captive-ape-associated lineages have independently acquired gene complexes that encode functions related to host mucin metabolism. Our results support the finding of high genome fluidity in , in that several strains, in moving from humans to captive apes, have rapidly gained large genomic regions that augment metabolic properties not previously present in their relatives.
PubMed: 37961372
DOI: 10.1101/2023.10.20.563286 -
Foods (Basel, Switzerland) Oct 2022Fermentation is one of the oldest known production processes and the most technologically valuable in terms of the food industry. In recent years, increasing nutrition... (Review)
Review
Fermentation is one of the oldest known production processes and the most technologically valuable in terms of the food industry. In recent years, increasing nutrition and health awareness has also changed what is expected from fermentation technology, and the production of healthier foods has started to come a little more forward rather than increasing the shelf life and organoleptic properties of foods. Therefore, in addition to traditional microorganisms, a new generation of (novel) microorganisms has been discovered and research has shifted to this point. Novel microorganisms are known as either newly isolated genera and species from natural sources or bacterial strains derived from existing bacteria. Although novel microorganisms are mostly studied for their use in novel food production in terms of gut-microbiota modulation, recent innovative food research highlights their fermentative effects and usability, especially in food modifications. Herein, , , , , and () can play key roles in future candidate microorganisms for fermentation technology in foods. However, there is also some confusion about the safety issues related to the use of these novel microorganisms. This review paper focuses on certain novel candidate microorganisms for fermentation technology with a deep view of their functions, benefits, and safety issues.
PubMed: 36230150
DOI: 10.3390/foods11193074 -
Microbiology Spectrum Sep 2023Acute pancreatitis (AP) is a type of digestive system disease with high mortality. Previous studies have shown that gut microbiota can participate in developing and...
Acute pancreatitis (AP) is a type of digestive system disease with high mortality. Previous studies have shown that gut microbiota can participate in developing and treating acute pancreatitis by affecting the host's metabolism. In this study, we followed 20 AP patients to generate longitudinal gut microbiota profiles and activity during disease (before treatment, on the third day of treatment, and 1 month after discharge). We analyzed species composition and metabolic pathways' changes across the treatment phase, severity, and etiology. The diversity of the gut microbiome of patients with AP did not show much variation with treatment. In contrast, the metabolic functions of the gut microbiota, such as the essential chemical reactions that produce energy and maintain life, were partially reinstated after treatment. The severe AP (SAP) patients contained less beneficial bacteria (i.e., , and ) and weaker sugar degradation function than mild AP patients before treatment. Moreover, etiology was one of the drivers of gut microbiome composition and explained the 3.54% variation in species' relative abundance. The relative abundance of pathways related to lipid synthesis was higher in the gut of hyperlipidemia AP patients than in biliary AP patients. The composition and functional profiles of the gut microbiota reflect the severity and etiology of AP. Otherwise, we also identified bacterial species associated with SAP, i.e., sp 57_20 and , which have the potential to identify the SAP at an early stage. IMPORTANCE Acute pancreatitis (AP) is a type of digestive system disease with high mortality. Previous studies have shown that gut microbiota can participate in the development and treatment of acute pancreatitis by affecting the host's metabolism. However, fewer studies acquired metagenomic sequencing data to associate species to functions intuitively and performed longitudinal analysis to explore how gut microbiota influences the development of AP. We followed 20 AP patients to generate longitudinal gut microbiota profiles and activity during disease and studied the differences in intestinal flora under different severities and etiologies. We have two findings. First, the gut microbiota profile has the potential to identify the severity and etiology of AP at an early stage. Second, gut microbiota likely acts synergistically in the development of AP. This study provides a reference for characterizing the driver flora of severe AP to identify the severity of acute pancreatitis at an early stage.
PubMed: 37698429
DOI: 10.1128/spectrum.00829-23 -
Cell Reports Aug 2020A beneficial gut Bacteroides-folate-liver pathway regulating lipid metabolism is demonstrated. Oral administration of a Ganoderma meroterpene derivative (GMD)...
A beneficial gut Bacteroides-folate-liver pathway regulating lipid metabolism is demonstrated. Oral administration of a Ganoderma meroterpene derivative (GMD) ameliorates nonalcoholic hepatic steatosis in the liver of fa/fa rats by reducing endotoxemia, enhancing lipid oxidation, decreasing de novo lipogenesis, and suppressing lipid export from the liver. An altered gut microbiota with an increase of butyrate and folate plays a causative role in the effects of GMD. The commensal bacteria Bacteroides xylanisolvens, Bacteroides thetaiotaomicron, Bacteroides dorei, and Bacteroides uniformis, which are enriched by GMD, are major contributors to the increased gut folate. Administration of live B. xylanisolvens reduces hepatic steatosis and enhances the folate-mediated signaling pathways in mice. Knockout of the folate biosynthetic folp gene in B. xylanisolvens blocks its folate production and beneficial effects. This work confirms the therapeutic potential of GMD and B. xylanisolvens in alleviating nonalcoholic hepatic steatosis and provides evidence for benefits of the gut Bacteroides-folate-liver pathway.
Topics: Animals; Bacteroides; Gastrointestinal Microbiome; Humans; Liver; Male; Mice; Non-alcoholic Fatty Liver Disease
PubMed: 32783933
DOI: 10.1016/j.celrep.2020.108005 -
Frontiers in Immunology 2023Autism Spectrum Disorders (ASD) are defined as a group of pervasive neurodevelopmental disorders, and the heterogeneity in the symptomology and etiology of ASD has long...
BACKGROUND
Autism Spectrum Disorders (ASD) are defined as a group of pervasive neurodevelopmental disorders, and the heterogeneity in the symptomology and etiology of ASD has long been recognized. Altered immune function and gut microbiota have been found in ASD populations. Immune dysfunction has been hypothesized to involve in the pathophysiology of a subtype of ASD.
METHODS
A cohort of 105 ASD children were recruited and grouped based on IFN-γ levels derived from stimulated γδT cells. Fecal samples were collected and analyzed with a metagenomic approach. Comparison of autistic symptoms and gut microbiota composition was made between subgroups. Enriched KEGG orthologues markers and pathogen-host interactions based on metagenome were also analyzed to reveal the differences in functional features.
RESULTS
The autistic behavioral symptoms were more severe for children in the IFN-γ-high group, especially in the body and object use, social and self-help, and expressive language performance domains. LEfSe analysis of gut microbiota revealed an overrepresentation of , , and and underrepresentation of and in children with higher IFN-γ level. Decreased metabolism function of carbohydrate, amino acid and lipid in gut microbiota were found in the IFN-γ-high group. Additional functional profiles analyses revealed significant differences in the abundances of genes encoding carbohydrate-active enzymes between the two groups. And enriched phenotypes related to infection and gastroenteritis and underrepresentation of one gut-brain module associated with histamine degradation were also found in the IFN-γ-High group. Results of multivariate analyses revealed relatively good separation between the two groups.
CONCLUSIONS
Levels of IFN-γ derived from γδT cell could serve as one of the potential candidate biomarkers to subtype ASD individuals to reduce the heterogeneity associated with ASD and produce subgroups which are more likely to share a more similar phenotype and etiology. A better understanding of the associations among immune function, gut microbiota composition and metabolism abnormalities in ASD would facilitate the development of individualized biomedical treatment for this complex neurodevelopmental disorder.
Topics: Humans; Gastrointestinal Microbiome; Autistic Disorder; Behavioral Symptoms; Amino Acids; Autism Spectrum Disorder
PubMed: 36875075
DOI: 10.3389/fimmu.2023.1100816