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Cell Host & Microbe Feb 2022Polysaccharide utilization loci (PULs) are co-regulated bacterial genes that sense nutrients and enable glycan digestion. Human gut microbiome members, notably...
Polysaccharide utilization loci (PULs) are co-regulated bacterial genes that sense nutrients and enable glycan digestion. Human gut microbiome members, notably Bacteroides, contain numerous PULs that enable glycan utilization and shape ecological dynamics. To investigate the role of PULs on fitness and inter-species interactions, we develop a CRISPR-based genome editing tool to study 23 PULs in Bacteroides uniformis (BU). BU PULs show distinct glycan-degrading functions and transcriptional coordination that enables the population to adapt upon loss of other PULs. Exploiting a BU mutant barcoding strategy, we demonstrate that in vitro fitness and BU colonization in the murine gut are enhanced by deletion of specific PULs and modulated by glycan availability. PULs mediate glycan-dependent interactions with butyrate producers that depend on the degradation mechanism and glycan utilization ability of the butyrate producer. Thus, PULs determine community dynamics and butyrate production and provide a selective advantage or disadvantage depending on the nutritional landscape.
Topics: Animals; Bacterial Proteins; Bacteroides; Gastrointestinal Microbiome; Genes, Bacterial; Genetic Fitness; Humans; Mice; Polysaccharides
PubMed: 34995484
DOI: 10.1016/j.chom.2021.12.006 -
BMC Pediatrics Oct 2023Sepsis is a life-threatening multiple-organ injury caused by disordered host immune response to microbial infection. However, the correlation between gut microbiota...
Sepsis is a life-threatening multiple-organ injury caused by disordered host immune response to microbial infection. However, the correlation between gut microbiota dysbiosis and immune indicators remains unexplored. To address this gap in knowledge, we carried out 16 S rDNA sequencing, analyzed clinical fecal samples from children with sepsis (n = 30) and control children (n = 25), and obtained immune indicators, including T cell subtypes (CD3, CD3CD4, CD3CD8, and CD4/CD8), NK cells, cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ), and immunoglobulin indices (IgA, IgE, IgM and IgG). In addition, we analyzed the correlation between gut microbiota dysbiosis and immune indicators, and evaluated the clinical discriminatory power of discovered bacterial biomarkers. We found that children with sepsis exhibited gut bacterial dysbiosis and low alpha diversity. The Spearman's rank correlation coefficient suggested that Rhodococcus erythropolis had a significantly positive correlation with IFN-γ and CD3 T cells. Klebsiella pneumoniae and Streptococcus mitis were significantly correlated with NK cells. Bacteroides uniformis was significantly positively correlated with IgM and erythrocyte sedimentation rate, and Eubacterium eligens was significantly positively correlated with IL-4 and CD3CD8 T cells. The biomarkers discovered in this study had strong discriminatory power. These changes in the gut microbiome may be closely related to immunologic dysfunction and to the development or exacerbation of sepsis. However, a large sample size is required for verification.
Topics: Humans; Child; Gastrointestinal Microbiome; CD8-Positive T-Lymphocytes; Dysbiosis; Interleukin-4; Sepsis; Bacteria; Biomarkers; Immunoglobulin M
PubMed: 37845615
DOI: 10.1186/s12887-023-04349-8 -
Nutrients Feb 2020The formulation of next-generation probiotics requires competent preclinical studies to show their efficacy and safety status. This study aims to confirm the safety of...
The formulation of next-generation probiotics requires competent preclinical studies to show their efficacy and safety status. This study aims to confirm the safety of the prolonged oral use of CECT 7771, a strain that protected against metabolic disorders and obesity in preclinical trials, in a sub-chronic 90 day trial in animals. The safety assessment was conducted in male and female Wistar rats ( = 50) administered increasing doses (10 CFU/day, 10 CFU/day, or 10 CFU/day) of CECT 7771, 10 CFU/day of ATCC 15707, which complies with the qualifying presumption of safety (QPS) status of the EU, or vehicle (placebo), as the control. Pancreatic, liver, and kidney functions and cytokine concentrations were analyzed. Bacterial translocation to peripheral tissues was evaluated, and colon integrity was investigated histologically. No adverse metabolic or tissue integrity alterations were associated with treatments; however, alanine aminotransferase levels and the ratio of anti-inflammatory to pro-inflammatory cytokines in serum indicated a potentially beneficial role of CECT 7771 at specific doses. Additionally, the microbial community structure was modified by the interventions, and potentially beneficial gut bacteria were increased. The results indicated that the oral consumption of CECT 7771 during a sub-chronic 90 day study in rats did not raise safety concerns.
Topics: Animals; Bacteroides; Cytokines; Female; Gastrointestinal Microbiome; Male; Microbiota; Probiotics; Rats; Rats, Wistar
PubMed: 32093252
DOI: 10.3390/nu12020551 -
Microorganisms Apr 2021Intestinal phages are abundant and important components of gut microbiota, yet the isolated and characterized representatives that infect abundant gut bacteria are...
Intestinal phages are abundant and important components of gut microbiota, yet the isolated and characterized representatives that infect abundant gut bacteria are sparse. Here we describe the isolation of human intestinal phages infecting . is one of the most common bacterial groups in the global human gut microbiota; however, to date not many specific phages are known. Phages isolated in this study belong to a novel viral genus, Bacuni, within the family. Their genomes encode diversity-generating retroelements (DGR), which were shown in other bacteriophages to promote phage adaptation to rapidly changing environmental conditions and to broaden their host range. Three isolated phages showed 99.83% genome identity but one of them infected a distinct strain. The tropism of Bacuni phages appeared to be dependent on the interplay of DGR mediated sequence variations of gene encoding putative phage fimbrial tip proteins and mutations in host genes coding for outer-membrane proteins. We found prophages with up to 85% amino acid similarity over two-thirds of the Bacuni phage genome in the and sp. genomes. Despite the abundance of within the human microbiome, we found Bacuni phages only in a limited subset of published gut metagenomes.
PubMed: 33919474
DOI: 10.3390/microorganisms9050892 -
Frontiers in Nutrition 2022Lychee pulp phenolics (LPP) is mainly catabolized in the host colon, increasing the abundances of and . Herein, five selected gut microbial strains (, and ) were...
Lychee pulp phenolics (LPP) is mainly catabolized in the host colon, increasing the abundances of and . Herein, five selected gut microbial strains (, and ) were separately incubated with LPP to ascertain the specific strains participating in phenolic metabolism and the corresponding metabolites. The results indicated that , and were involved in LPP utilization, contributing to 52.37, 28.33, and 45.11% of LPP degradation after 48 h fermentation, respectively. Unprecedentedly, the metabolic pathway of the major phenolic compound quercetin-3--rutinose-7--α-L-rhamnoside by , appeared to be the direct fission of C-ring at C2-O1 and C3-C4 bonds, which was proved from the occurrence of two substances with the deprotonated molecule [M-H] ion at 299 and 459, respectively. Meanwhile, it was fully confirmed that participated in the catabolism of isorhamnetin glycoside and procyanidin B2. In the culture, kaempferol was synthesized through dehydroxylation of quercetin which could be catabolized into alphitonin by . Furthermore, LPP metabolites exerted higher antioxidant activity than their precursors and gave clues to understand the interindividual differences for phenolic metabolism by gut microbiota.
PubMed: 35369057
DOI: 10.3389/fnut.2022.849439 -
Journal of Clinical Medicine Apr 2021Fecal microbiota transplantation following triple-antibiotic therapy (amoxicillin/fosfomycin/metronidazole) improves dysbiosis caused by reduced Bacteroidetes diversity...
Fecal microbiota transplantation following triple-antibiotic therapy (amoxicillin/fosfomycin/metronidazole) improves dysbiosis caused by reduced Bacteroidetes diversity in patients with ulcerative colitis (UC). We investigated the correlation between Bacteroidetes species abundance and UC activity. Fecal samples from 34 healthy controls and 52 patients with active UC (Lichtiger's clinical activity index ≥5 or Mayo endoscopic subscore ≥1) were subjected to next-generation sequencing with as a target in bacterial metagenome analysis. A multiplex gene expression assay using colonoscopy-harvested mucosal tissues determined the involvement of Bacteroidetes species in the mucosal immune response. In patients with UC, six Bacteroides species exhibited significantly lower relative abundance, and twelve Bacteroidetes species were found significantly correlated with at least one metric of disease activity. The abundance of five Bacteroidetes species (, , , , and ) was correlated with three metrics, and their cumulative relative abundance was strongly correlated with the sum of Mayo endoscopic subscore (R = -0.71, = 2 × 10). Five genes (, , , , and ) associated with UC pathogenesis were expressed by the 12 key species. The loss of key species may exacerbate UC activity, serving as potential biomarkers.
PubMed: 33920646
DOI: 10.3390/jcm10081749 -
PloS One 2016Bacteroides uniformis CECT 7771 is a potential probiotic strain, originally isolated from the stools of healthy breast-feed infants. The strain showed pre-clinical...
BACKGROUND
Bacteroides uniformis CECT 7771 is a potential probiotic strain, originally isolated from the stools of healthy breast-feed infants. The strain showed pre-clinical efficacy in a mouse obesity model. The objective of this study was to evaluate its potential toxicity and translocation ability after acute oral administration to mice.
METHODS AND FINDINGS
A safety study was conducted in immunocompetent and immunosuppressed C57BL-6 mice. Both mouse groups (n = 10 per group) were fed orally 2 x 10(9) colony forming units (cfu)/day of B. uniformis CECT 7771 or placebo by gavage for 6 days. Throughout this time, feed and water intake and body weight were monitored. Afterwards, mice were sacrificed and biological samples were collected to analyze blood and urine biochemistry, inflammatory and immune markers; gut mucosal histology and bacterial translocation to peripheral tissues. The results demonstrated that acute ingestion of this Bacteroides strain had no adverse effects on the animals' general health status or food intake, nor did it affect biochemical indicators of liver, kidney and pancreatic function or gut mucosal histology. Findings also demonstrated that administration did not lead to bacterial translocation to blood, liver or mesenteric lymph nodes. B. uniformis CECT 7771 also downregulated gene and protein expression (iNOS and PPAR-γ) and inflammatory cytokines induced by immunosuppression.
CONCLUSIONS
The findings indicate that the acute oral consumption of B. uniformis CECT 7771 does not raise safety concerns in mice. Further studies in humans should be conducted.
Topics: Animals; Bacteroides; Breast Feeding; Cytokines; Feces; Humans; Infant; Kidney; Liver; Mice; Mice, Inbred C57BL; Nitric Oxide Synthase Type II; PPAR gamma; Pancreas; Probiotics
PubMed: 26784747
DOI: 10.1371/journal.pone.0145503 -
PloS One 2021Obesity is the cause of cardiovascular diseases and other diseases, leading to increased medical costs, and causing a great burden to individuals, families and society....
BACKGROUND
Obesity is the cause of cardiovascular diseases and other diseases, leading to increased medical costs, and causing a great burden to individuals, families and society. The prevalence of obesity is increasing and has become a global health problem. There is growing evidence that gut microbiota plays an important role in obesity. In this article, we revealed the differences in the gut microbiota between 21 people with obesity and 21 control subjects, and predicted the functional potential changes by 16S rRNA sequencing of the fecal bacteria of the subjects.
METHODS
The raw sequencing data of 21 healthy Beijing volunteers was downloaded from Microbial Genome Database System. Microbial 16S rRNA genes of 21 adults with obesity were sequenced on an Illumina MiSeq instrument and analyzed by using bioinformatics and statistical methods.
RESULTS
The diversity of gut microbiota in people with obesity decreased significantly. There were significant differences in gut microbiota between the Obesity and Control group at different levels. At the phylum level, Firmicutes, Bacteroidetes, Actinobacteria and Fusobacteria are significantly different between the Obesity and Control group. In people with obesity, the ratio of Firmicutes/Bacteroidetes decreased significantly. At the genus level, there were significant differences among the 16 major genera, of which four genera Prevotella, Megamonas, Fusobacterium and Blautia increased significantly in people with obesity, while the remaining 12 genera, Faecalibacterium, Lachnospiracea_incertae_sedis, Gemmiger and Clostridium XlVa, etc. decreased significantly. At the species level, nine species including Bacteroides uniformis and Prevotella copri had significant differences. Compared with the control group, subjects with obesity were abnormalities in 57 pathways, mainly in Carbohydrate metabolism and Lipid metabolism.
CONCLUSIONS
Overall, our study revealed differences in the gut microbiota between people with obesity and control subjects, providing novel target for the treatment of individuals with obesity.
Topics: Adult; Bacteroides; Dysbiosis; Gastrointestinal Microbiome; Humans; Male; Prevotella; RNA, Ribosomal, 16S
PubMed: 34375351
DOI: 10.1371/journal.pone.0255446 -
Microbiome Apr 2023Psychological health risk is one of the most severe and complex risks in manned deep-space exploration and long-term closed environments. Recently, with the in-depth...
BACKGROUND
Psychological health risk is one of the most severe and complex risks in manned deep-space exploration and long-term closed environments. Recently, with the in-depth research of the microbiota-gut-brain axis, gut microbiota has been considered a new approach to maintain and improve psychological health. However, the correlation between gut microbiota and psychological changes inside long-term closed environments is still poorly understood. Herein, we used the "Lunar Palace 365" mission, a 1-year-long isolation study in the Lunar Palace 1 (a closed manned Bioregenerative Life Support System facility with excellent performance), to investigate the correlation between gut microbiota and psychological changes, in order to find some new potential psychobiotics to maintain and improve the psychological health of crew members.
RESULTS
We report some altered gut microbiota that were associated with psychological changes in the long-term closed environment. Four potential psychobiotics (Bacteroides uniformis, Roseburia inulinivorans, Eubacterium rectale, and Faecalibacterium prausnitzii) were identified. On the basis of metagenomic, metaproteomic, and metabolomic analyses, the four potential psychobiotics improved mood mainly through three pathways related to nervous system functions: first, by fermenting dietary fibers, they may produce short-chain fatty acids, such as butyric and propionic acids; second, they may regulate amino acid metabolism pathways of aspartic acid, glutamic acid, tryptophan, etc. (e.g., converting glutamic acid to gamma-aminobutyric acid; converting tryptophan to serotonin, kynurenic acid, or tryptamine); and third, they may regulate other pathways, such as taurine and cortisol metabolism. Furthermore, the results of animal experiments confirmed the positive regulatory effect and mechanism of these potential psychobiotics on mood.
CONCLUSIONS
These observations reveal that gut microbiota contributed to a robust effect on the maintenance and improvement of mental health in a long-term closed environment. Our findings represent a key step towards a better understanding the role of the gut microbiome in mammalian mental health during space flight and provide a basis for future efforts to develop microbiota-based countermeasures that mitigate risks to crew mental health during future long-term human space expeditions on the moon or Mars. This study also provides an essential reference for future applications of psychobiotics to neuropsychiatric treatments. Video Abstract.
Topics: Animals; Humans; Gastrointestinal Microbiome; Moon; Multiomics; Tryptophan; Glutamates; Mammals
PubMed: 37095530
DOI: 10.1186/s40168-023-01506-0 -
Frontiers in Cell and Developmental... 2021Osteoporosis (OP) is a chronic disease in the elderly, and China is entering an aging demographic trend. In recent years, increasing evidence has demonstrated that...
Osteoporosis (OP) is a chronic disease in the elderly, and China is entering an aging demographic trend. In recent years, increasing evidence has demonstrated that probiotics can treat osteoporosis. This study aimed to explore the relevant mechanisms and to validate the beneficial effect on osteoporosis by high-throughput metagenome-wide gene sequencing in humans. In this study, compared with controls, several species had altered abundances, and specific functional pathways were found in the OP group. At the species level, the species that had increased in OP individuals were positively correlated to bone resorption markers and negatively correlated to 25-OH-D3 and bone formation markers, with showing the strongest relevance, followed by , , and Additionally, , enriched in the OP group, was positively correlated to inflammation indicators that included white blood cell (WBC), neutrophil count (NEC), and the neutrophil-to-lymphocyte ratio (NLR) ( < 0.05). Conversely, the levels of , , , , and were increased in the control group, which had a negative correlation with bone resorption markers and positive correlation with bone formation markers and 25-OH-D3. Additionally, had a negative correlation with inflammation indicators (WBC, NEC, and NLR) and the above pathways ( < 0.05). Functional prediction revealed that 106 metabolic pathways, enriched in the OP group, were significantly higher than in the control group ( < 0.05). In particular, pathways related to LPS biosynthesis, phytate degradation, lactate acid, and ethanol fermentation were more abundant in the OP group than in the control and were positively related to WBC and NEC. Taken together, several species with altered abundances and specific functional pathways were found in OP individuals. The role of phytases in OP provides novel epidemiological evidence to elucidate the underlying microbiota-relevant mechanisms in bone mineralization and should be explored further.
PubMed: 34869341
DOI: 10.3389/fcell.2021.752990