-
Nature Oct 2022Tobacco smoking is positively correlated with non-alcoholic fatty liver disease (NAFLD), but the underlying mechanism for this association is unclear. Here we report...
Tobacco smoking is positively correlated with non-alcoholic fatty liver disease (NAFLD), but the underlying mechanism for this association is unclear. Here we report that nicotine accumulates in the intestine during tobacco smoking and activates intestinal AMPKα. We identify the gut bacterium Bacteroides xylanisolvens as an effective nicotine degrader. Colonization of B. xylanisolvens reduces intestinal nicotine concentrations in nicotine-exposed mice, and it improves nicotine-exacerbated NAFLD progression. Mechanistically, AMPKα promotes the phosphorylation of sphingomyelin phosphodiesterase 3 (SMPD3), stabilizing the latter and therefore increasing intestinal ceramide formation, which contributes to NAFLD progression to non-alcoholic steatohepatitis (NASH). Our results establish a role for intestinal nicotine accumulation in NAFLD progression and reveal an endogenous bacterium in the human intestine with the ability to metabolize nicotine. These findings suggest a possible route to reduce tobacco smoking-exacerbated NAFLD progression.
Topics: Animals; Humans; Mice; Bacteria; Ceramides; Nicotine; Non-alcoholic Fatty Liver Disease; Sphingomyelin Phosphodiesterase; Tobacco Smoking; Intestines; AMP-Activated Protein Kinases; Disease Progression
PubMed: 36261549
DOI: 10.1038/s41586-022-05299-4 -
BMC Genomics Feb 2016Diet and particularly dietary fibres have an impact on the gut microbiome and play an important role in human health and disease. Pectin is a highly consumed dietary...
BACKGROUND
Diet and particularly dietary fibres have an impact on the gut microbiome and play an important role in human health and disease. Pectin is a highly consumed dietary fibre found in fruits and vegetables and is also a widely used additive in the food industry. Yet there is no information on the effect of pectin on the human gut microbiome. Likewise, little is known on gut pectinolytic bacteria and their enzyme systems. This study was undertaken to investigate the mechanisms of pectin degradation by the prominent human gut symbiont Bacteroides xylanisolvens.
RESULTS
Transcriptomic analyses of B. xylanisolvens XB1A grown on citrus and apple pectins at mid- and late-log phases highlighted six polysaccharide utilization loci (PUL) that were overexpressed on pectin relative to glucose. The PUL numbers used in this report are those given by Terrapon et al. (Bioinformatics 31(5):647-55, 2015) and found in the PUL database: http://www.cazy.org/PULDB/. Based on their CAZyme composition, we propose that PUL 49 and 50, the most overexpressed PULs on both pectins and at both growth phases, are involved in homogalacturonan (HG) and type I rhamnogalacturonan (RGI) degradation, respectively. PUL 13 and PUL 2 could be involved in the degradation of arabinose-containing side chains and of type II rhamnogalacturonan (RGII), respectively. Considering that HG is the most abundant moiety (>70%) within pectin, the importance of PUL 49 was further investigated by insertion mutagenesis into the susC-like gene. The insertion blocked transcription of the susC-like and the two downstream genes (susD-like/FnIII). The mutant showed strong growth reduction, thus confirming that PUL 49 plays a major role in pectin degradation.
CONCLUSION
This study shows the existence of six PULs devoted to pectin degradation by B. xylanisolvens, one of them being particularly important in this function. Hence, this species deploys a very complex enzymatic machinery that probably reflects the structural complexity of pectin. Our findings also highlight the metabolic plasticity of B. xylanisolvens towards dietary fibres that contributes to its competitive fitness within the human gut ecosystem. Wider functional and ecological studies are needed to understand how dietary fibers and especially plant cell wall polysaccharides drive the composition and metabolism of the fibrolytic and non-fibrolytic community within the gut microbial ecosystem.
Topics: Bacteroides; Citrus; Dietary Fiber; Genetic Loci; Malus; Mutagenesis; Pectins; RNA, Bacterial; Sequence Analysis, RNA; Transcriptome
PubMed: 26920945
DOI: 10.1186/s12864-016-2472-1 -
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 -
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 -
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 -
Microbiome Apr 2021The gut phageome comprises a complex phage community of thousands of individual strains, with a few highly abundant bacteriophages. CrAss-like phages, which infect...
BACKGROUND
The gut phageome comprises a complex phage community of thousands of individual strains, with a few highly abundant bacteriophages. CrAss-like phages, which infect bacteria of the order Bacteroidales, are the most abundant bacteriophage family in the human gut and make an important contribution to an individual's core virome. Based on metagenomic data, crAss-like phages form a family, with four sub-families and ten candidate genera. To date, only three representatives isolated in pure culture have been reported: ΦcrAss001 and two closely related phages DAC15 and DAC17; all are members of the less abundant candidate genus VI. The persistence at high levels of both crAss-like phage and their Bacteroidales hosts in the human gut has not been explained mechanistically, and this phage-host relationship can only be properly studied with isolated phage-host pairs from as many genera as possible.
RESULTS
Faeces from a healthy donor with high levels of crAss-like phage was used to initiate a faecal fermentation in a chemostat, with selected antibiotics chosen to inhibit rapidly growing bacteria and selectively enrich for Gram-negative Bacteroidales. This had the objective of promoting the simultaneous expansion of crAss-like phages on their native hosts. The levels of seven different crAss-like phages expanded during the fermentation, indicating that their hosts were also present in the fermenter. The enriched supernatant was then tested against individual Bacteroidales strains isolated from the same faecal sample. This resulted in the isolation of a previously uncharacterised crAss-like phage of candidate genus IV of the proposed Alphacrassvirinae sub-family, ΦcrAss002, that infects the gut commensal Bacteroides xylanisolvens. ΦcrAss002 does not form plaques or spots on lawns of sensitive cells, nor does it lyse liquid cultures, even at high titres. In keeping with the co-abundance of phage and host in the human gut, ΦcrAss002 and Bacteroides xylanisolvens can also co-exist at high levels when co-cultured in laboratory media.
CONCLUSIONS
We report the isolation and characterisation of ΦcrAss002, the first representative of the proposed Alphacrassvirinae sub-family of crAss-like phages. ΦcrAss002 cannot form plaques or spots on bacterial lawns but can co-exist with its host, Bacteroides xylanisolvens, at very high levels in liquid culture without impacting on bacterial numbers. Video abstract.
Topics: Bacteriophages; Bacteroides; Gastrointestinal Microbiome; Humans; Phylogeny
PubMed: 33845877
DOI: 10.1186/s40168-021-01036-7 -
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 -
The Journal of Antimicrobial... May 2022We sought to characterize the carbapenem resistance mechanism of Bacteroides xylanisolvens 14880, an imipenem-resistant strain from Germany, and assess its prevalence.
OBJECTIVES
We sought to characterize the carbapenem resistance mechanism of Bacteroides xylanisolvens 14880, an imipenem-resistant strain from Germany, and assess its prevalence.
METHODS
Antimicrobial susceptibilities were determined using agar dilution or Etest methodology and specific imipenemase activity was detected. The genomic sequence of B. xylanisolvens 14880 was determined and analysed for antibiotic resistance genes and genomic islands. We also used gene transfer to a carbapenem susceptible host, along with 5'-RACE, conventional PCR with capillary sequencing and RT-PCR-based screening.
RESULTS
B. xylanisolvens 14880 displayed resistance to carbapenems and produced high specific imipenemase activity. Its genomic sequence was 6.1 Mbp and a class B1 β-lactamase gene (termed crxA) was detected in it. crxA was carried on a putative genomic island with insertion sequence (IS) elements and a putative GNAT (Gcn5-like acetyltransferase) toxin gene. Promoter localization by 5'-RACE and gene targeting to an imipenem-susceptible Bacteroides host indicated that it is activated by an IS1380-like IS element and it can confer carbapenem resistance. The PCR screening of Bacteroides strains showed that crxA was specific to B. xylanisolvens with a carriage rate of 16.7%.
CONCLUSIONS
B. xylanisolvens strains can harbour a carbapenem resistance gene, which has many similarities to the 'cfiA system': metallo-β-lactamase (MBL), IS element activation, carriage of a GNAT toxin gene, specific for a unique Bacteroides species with a significant prevalence.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Bacteroides; Bacteroides fragilis; Carbapenems; DNA Transposable Elements; Genomics; Imipenem; Microbial Sensitivity Tests; beta-Lactamases
PubMed: 35296904
DOI: 10.1093/jac/dkac088 -
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 -
Applied and Environmental Microbiology Jan 2012Besides conferring some health benefit to the host, a bacterial strain must present an unambiguous safety status to be considered a probiotic. We here present the...
Besides conferring some health benefit to the host, a bacterial strain must present an unambiguous safety status to be considered a probiotic. We here present the preliminary safety evaluation of a new Bacteroides xylanisolvens strain (DSM 23964) isolated from human feces. First results suggest that it may be able to provide probiotic health benefits. Its identity was confirmed by biochemical analysis, by sequencing of its 16S rRNA genes, and by DNA-DNA hybridization. Virulence determinants known to occur in the genus Bacteroides, such the bft enterotoxin and other enzymatic activities involved in the degradation of the extracellular matrix and the capsular polysaccharide PS A, were absent in this strain. The investigation of the antibiotic susceptibility indicated that strain DSM 23964 was sensitive to metronidazole, meropenem agents, and clindamycin. Resistance to penicillin and ampicillin was identified to be conferred by the β-lactamase cepA gene and could therefore be restored by adding β-lactamase inhibitors. The localization of the cepA gene in the genome of strain DSM 23964 and the absence of detectable plasmids further suggest that a transfer of β-lactamase activity or the acquisition of other antibiotic resistances are highly improbable. Taken together, the presented data indicate that the strain B. xylanisolvens DSM 23964 has no virulence potential. Since it also resists the action of gastric enzymes and low-pH conditions, this strain is an interesting candidate for further investigation of its safety and potential health-promoting properties.
Topics: Anti-Bacterial Agents; Bacterial Typing Techniques; Bacteroides; Cluster Analysis; DNA, Bacterial; DNA, Ribosomal; Feces; Humans; Microbial Sensitivity Tests; Nucleic Acid Hybridization; Phylogeny; Plasmids; Probiotics; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Virulence Factors; beta-Lactamases
PubMed: 22101046
DOI: 10.1128/AEM.06641-11