-
MSystems Apr 2024The microbial utilization of dietary carbohydrates is closely linked to the pivotal role of the gut microbiome in human health. Inherent to the modulation of complex...
UNLABELLED
The microbial utilization of dietary carbohydrates is closely linked to the pivotal role of the gut microbiome in human health. Inherent to the modulation of complex microbial communities, a prebiotic implies the selective utilization of a specific substrate, relying on the metabolic capacities of targeted microbes. In this study, we investigated the metabolic capacities of 17 commensal bacteria of the human gut microbiome toward dietary carbohydrates with prebiotic potential. First, experiments allowed the classification of bacterial growth and fermentation profiles in response to various carbon sources, including agave inulin, corn fiber, polydextrose, and citrus pectin. The influence of phylogenetic affiliation appeared to statistically outweigh carbon sources in determining the degree of carbohydrate utilization. Second, we narrowed our focus on six commensal bacteria representative of the and phyla to perform an untargeted high-resolution liquid chromatography-mass spectrometry metabolomic analysis: , , , , and exhibited distinct metabolomic profiles in response to different carbon sources. The relative abundance of bacterial metabolites was significantly influenced by dietary carbohydrates, with these effects being strain-specific and/or carbohydrate-specific. Particularly, the findings indicated an elevation in short-chain fatty acids and other metabolites, including succinate, gamma-aminobutyric acid, and nicotinic acid. These metabolites were associated with putative health benefits. Finally, an RNA-Seq transcriptomic approach provided deeper insights into the underlying mechanisms of carbohydrate metabolization. Restricting our focus on four commensal bacteria, including , and , carbon sources did significantly modulate the level of bacterial genes related to the enzymatic machinery involved in the metabolization of dietary carbohydrates. This study provides a holistic view of the molecular strategies induced during the dynamic interplay between dietary carbohydrates with prebiotic potential and gut commensal bacteria.
IMPORTANCE
This study explores at a molecular level the interactions between commensal health-relevant bacteria and dietary carbohydrates holding prebiotic potential. We showed that prebiotic breakdown involves the specific activation of gene expression related to carbohydrate metabolism. We also identified metabolites produced by each bacteria that are potentially related to our digestive health. The characterization of the functional activities of health-relevant bacteria toward prebiotic substances can yield a better application of prebiotics in clinical interventions and personalized nutrition. Overall, this study highlights the importance of identifying the impact of prebiotics at a low resolution of the gut microbiota to characterize the activities of targeted bacteria that can play a crucial role in our health.
Topics: Humans; Prebiotics; Dietary Carbohydrates; Phylogeny; Bacteria; Carbon
PubMed: 38441031
DOI: 10.1128/msystems.01401-23 -
Microbiome Feb 2024Chondroitin sulfate (CS) has widely been used as a symptomatic slow-acting drug or a dietary supplement for the treatment and prevention of osteoarthritis. However, CS...
Chondroitin sulfate (CS) has widely been used as a symptomatic slow-acting drug or a dietary supplement for the treatment and prevention of osteoarthritis. However, CS could not be absorbed after oral intake due to its polyanionic nature and large molecular weight. Gut microbiota has recently been proposed to play a pivotal role in the metabolism of drugs and nutrients. Nonetheless, how CS is degraded by the human gut microbiota has not been fully characterized. In the present study, we demonstrated that each human gut microbiota was characterized with a unique capability for CS degradation. Degradation and fermentation of CS by the human gut microbiota produced significant amounts of unsaturated CS oligosaccharides (CSOSs) and short-chain fatty acids. To uncover which microbes were responsible for CS degradation, we isolated a total of 586 bacterial strains with a potential CS-degrading capability from 23 human fecal samples. Bacteroides salyersiae was a potent species for CS degradation in the human gut microbiota and produced the highest amount of CSOSs as compared to other well-recognized CS-degraders, including Bacteroides finegoldii, Bacteroides thetaiotaomicron, Bacteroides xylanisolvens, and Bacteroides ovatus. Genomic analysis suggested that B. salyersiae was armed with multiple carbohydrate-active enzymes that could potentially degrade CS into CSOSs. By using a spent medium assay, we further demonstrated that the unsaturated tetrasaccharide (udp4) produced by the primary degrader B. salyersiae could serve as a "public goods" molecule for the growth of Bacteroides stercoris, a secondary CS-degrader that was proficient at fermenting CSOSs but not CS. Taken together, our study provides insights into the metabolism of CS by the human gut microbiota, which has promising implications for the development of medical and nutritional therapies for osteoarthritis. Video Abstract.
Topics: Humans; Chondroitin Sulfates; Gastrointestinal Microbiome; Oligosaccharides; Osteoarthritis; Bacteroides
PubMed: 38419055
DOI: 10.1186/s40168-024-01768-2 -
European Journal of Nutrition Apr 2024To investigate the relationships between the habitual diet, the protein to fiber ratio (P/F), and the gut microbiome in one Italian and one Dutch cohort of healthy...
PURPOSE
To investigate the relationships between the habitual diet, the protein to fiber ratio (P/F), and the gut microbiome in one Italian and one Dutch cohort of healthy subjects consuming an omnivore diet.
METHODS
The Italian cohort included 19 males (M_IT, BMI 25.2 ± 0.72 kg/m, age 25.4 ± 0.96 years) and 20 females (F_IT, BMI 23.9 ± 0.81 kg/m, age 23.8 ± 0.54 years); the Dutch cohort included 30 females (F_NL, BMI: 23.9 ± 0.81 kg/m, age: 23.8 ± 0.54 years). Individual diets were recorded through Food Frequency Questionnaires and analyzed to assess the nutrient composition. Gut microbiome was assessed in fecal samples.
RESULTS
M_IT consumed higher levels of proteins than F_NL and F_IT, whereas dietary fiber intake did not differ among groups. Data showed that consumption of plant protein to animal protein (PP/AP) and PP to total proteins ratio can determine a differentiation of F_NL more than the absolute amount of dietary fiber. Conversely, the protein to fiber (P/F) and AP to total proteins better characterized M_IT. M_IT harbored the highest abundance of proteolytic microorganisms and the lowest microbial gene richness. Conversely, F_NL had more fiber-degrading microorganisms like Bacteroides thetaiotaomicron, Bacteroides xylanisolvens, Roseburia sp., Coprococcus eutactus and Parabacteroides along with the highest number of genes encoding carbohydrate-active enzymes and gene richness. It was predicted that by each unit decrease in the P/F a 3% increase in gene richness occurred.
CONCLUSION
Study findings suggested that dietary P/F, rather than the absolute amount of dietary fiber, could contribute to the shaping of the microbiome towards a more proteolytic or fiber-degrading gut ecosystem.
CLINICALTRIALS
gov Identifier NCT04205045-01-10-2018, retrospectively registered. Dutch Trial Register NTR7531-05-10-2018.
Topics: Male; Female; Animals; Humans; Young Adult; Adult; Gastrointestinal Microbiome; Diet; Carbohydrates; Dietary Fiber; Feces; Dietary Proteins; Microbiota; Italy
PubMed: 38151533
DOI: 10.1007/s00394-023-03308-4 -
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 -
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 -
Frontiers in Microbiology 2023Hyperuricemia is widespread in humans and birds which is a necessary physiological factor leading to gout. Studies have shown an inextricable relationship between gut...
INTRODUCTION
Hyperuricemia is widespread in humans and birds which is a necessary physiological factor leading to gout. Studies have shown an inextricable relationship between gut microbiota and hyperuricemia. This study explored the association between intestinal flora and hyperuricemia in Goslings.
METHODS AND RESULTS
The hyperuricemia model was established in gosling by a high protein diet (HPD). 16S rDNA sequencing showed that the cecal microbiota differed significantly between the HPD and control groups (fed with the normal protein). The abundance of was higher in the HPD group, while the were lower than in controls. To investigate the role of intestinal flora in hyperuricemia, the cecum microbiotas from the HPD group and the control group were transplanted to the newly born goslings by gavage. The serum uric acid levels of the goslings that transplanted the cecal microbiota of the HPD group were significantly higher than the goslings that transplanted the cecal microbiota of the controls. Furthermore, the transplantation of cecal microbiota also affects the production and excretion of uric acid in goslings. Then we identify the gut bacterium as an effective anti-hyperuricemia in the Goslings. reduces serum uric acid concentrations in hyperuricemia in the Goslings' model, and it can up-regulation ABCG2 mRNA expression in the kidney and down-regulation XDH mRNA expression in the liver.
DISCUSSION
The intestinal flora acts as a novel target for the therapeutic approach to hyperuricemia and gout, suggest is a possible route to therapy for hyperuricemia and gout in goslings.
PubMed: 37455728
DOI: 10.3389/fmicb.2023.1173856 -
Metabolomics : Official Journal of the... Jun 2023Gut bacteria play a crucial role in the metabolism of bile acids (BA). Whether an association exists between the fecal microbiota composition and circulating BA levels...
BACKGROUND
Gut bacteria play a crucial role in the metabolism of bile acids (BA). Whether an association exists between the fecal microbiota composition and circulating BA levels in humans is poorly understood. Here, we investigated the relationship between fecal microbiota diversity and composition with plasma levels of BA in young adults.
METHODS
Fecal microbiota diversity/composition was analyzed with 16S rRNA sequencing in 80 young adults (74% women; 21.9 ± 2.2 years old). Plasma levels of BA were measured using liquid chromatography-tandem mass spectrometry. PERMANOVA and Spearman correlation analyses were used to investigate the association between fecal microbiota parameters and plasma levels of BA.
RESULTS
Fecal microbiota beta (P = 0.025) and alpha diversity indexes of evenness (rho = 0.237, P = 0.033), Shannon (rho = 0.313, P = 0.004), and inverse Simpson (rho = 0.283, P = 0.010) were positively associated with plasma levels of the secondary BA glycolithocholic acid (GLCA). The relative abundance of genera belonging to the Firmicutes and Bacteroidetes phyla was positively correlated with plasma levels of GLCA (all rho ≥ 0.225, P ≤ 0.049). However, the relative abundance of species from Firmicutes and Bacteroidetes phyla were negatively correlated with plasma levels of primary and secondary BA (all rho ≤ - 0.220, P ≤ 0.045), except for the relative abundance of Bacteroides vulgatus, Alistipes onderdonkii, and Bacteroides xylanisolvens species (Bacteroidetes phylum) that were positively correlated with the plasma levels of GLCA.
CONCLUSIONS
The relative abundance of specific fecal bacteria species is associated with plasma levels of BA in young adults. However, further investigations are required to validate whether the composition of the gut microbiota can regulate the plasma concentrations of BA in humans.
Topics: Humans; Female; Young Adult; Adult; Male; Firmicutes; Bile Acids and Salts; RNA, Ribosomal, 16S; Metabolomics; Bacteria; Bacteroidetes
PubMed: 37278866
DOI: 10.1007/s11306-023-02016-8 -
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 -
Polymers Apr 2023Heparinase I (Hep I), which specifically degrades heparin to oligosaccharide or unsaturated disaccharide, has an important role in the production of low molecular weight...
Heparinase I (Hep I), which specifically degrades heparin to oligosaccharide or unsaturated disaccharide, has an important role in the production of low molecular weight heparin (LMWH). However, low productivity and stability of heparinase I hinders its applications. Here, a novel heparinase I (BxHep-I) was cloned from and overexpressed in soluble form in . The expression conditions of BxHep-I were optimized for an activity of 7144 U/L. BxHep-I had a specific activity of 57.6 U/mg at the optimal temperature and pH of 30 °C and pH 7.5, with the and of 0.79 mg/mL and 124.58 U/mg, respectively. BxHep-I catalytic activity could be enhanced by Ca and Mg, while strongly inhibited by Zn and Co. Purified BxHep-I displayed an outstanding thermostability with half-lives of 597 and 158 min at 30 and 37 °C, respectively, which are the highest half-lives ever reported for heparinases I. After storage at 4 °C for one week, BxHep-I retained 73% of its initial activity. Molecular docking revealed that the amino acids Asn25, Gln27, Arg88, Lys116, His156, Arg161, Gln228, Tyr356, Lys358, and Tyr362 form 13 hydrogen bonds with the substrate heparin disaccharides in the substrate binding domain and are mainly involved in the substrate binding of BxHep-I. These results suggest that the BxHep-I with high stability could be a candidate catalyst for the industrial production of LMWH.
PubMed: 37050390
DOI: 10.3390/polym15071776 -
Nutrients Mar 2023Alginate has been documented to prevent the development and progression of ulcerative colitis by modulating the gut microbiota. However, the bacterium that may mediate...
Alginate has been documented to prevent the development and progression of ulcerative colitis by modulating the gut microbiota. However, the bacterium that may mediate the anti-colitis effect of alginate has not been fully characterized. We hypothesized that alginate-degrading bacteria might play a role here since these bacteria could utilize alginate as a carbon source. To test this hypothesis, we isolated 296 strains of alginate-degrading bacteria from the human gut. AY11-1 was observed to have the best capability for alginate degradation. The degradation and fermentation of alginate by AY11-1 produced significant amounts of oligosaccharides and short-chain fatty acids. Further studies indicated that AY11-1 could alleviate body weight loss and contraction of colon length, reduce the incidences of bleeding and attenuate mucosal damage in dextran sulfate sodium (DSS)-fed mice. Mechanistically, AY11-1 improved gut dysbiosis and promoted the growth of probiotic bacteria, including spp. And , in diseased mice. Additionally, AY11-1 showed no oral toxicity and was well-tolerated in male and female mice. Altogether, we illustrate for the first time an anti-colitis effect of the alginate-degrading bacterium AY11-1. Our study paves the way for the development of AY11-1 as a next-generation probiotic bacterium.
Topics: Humans; Male; Female; Animals; Mice; Alginates; Gastrointestinal Microbiome; Colitis; Colon; Bacteria; Probiotics; Dextran Sulfate; Mice, Inbred C57BL; Disease Models, Animal
PubMed: 36986080
DOI: 10.3390/nu15061352