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Scientific Reports Sep 2017The gut microbiota generates a huge pool of unknown metabolites, and their identification and characterization is a key challenge in metabolomics. However, there are...
The gut microbiota generates a huge pool of unknown metabolites, and their identification and characterization is a key challenge in metabolomics. However, there are still gaps on the studies of gut microbiota and their chemical structures. In this investigation, an unusual class of bacterial sulfonolipids (SLs) is detected in mouse cecum, which was originally found in environmental microbes. We have performed a detailed molecular level characterization of this class of lipids by combining high-resolution mass spectrometry and liquid chromatography analysis. Eighteen SLs that differ in their capnoid and fatty acid chain compositions were identified. The SL called "sulfobacin B" was isolated, characterized, and was significantly increased in mice fed with high-fat diets. To reveal bacterial producers of SLs, metagenome analysis was acquired and only two bacterial genera, i.e., Alistipes and Odoribacter, were revealed to be responsible for their production. This knowledge enables explaining a part of the molecular complexity introduced by microbes to the mammalian gastrointestinal tract and can be used as chemotaxonomic evidence in gut microbiota.
Topics: Animals; Bacteroidetes; Cecum; Chromatography, Liquid; Diet, High-Fat; Gastrointestinal Microbiome; Lipids; Mass Spectrometry; Mice
PubMed: 28887494
DOI: 10.1038/s41598-017-10369-z -
Journal of Crohn's & Colitis Jul 2023Crohn's disease [CD] is a major subtype of inflammatory bowel diseases [IBD] with increasing incidence and prevalence. Results of studies using available small and large...
BACKGROUND AND AIMS
Crohn's disease [CD] is a major subtype of inflammatory bowel diseases [IBD] with increasing incidence and prevalence. Results of studies using available small and large animal models are often poorly translatable to patients, and few CD models show small intestinal pathology. Due to its similarities to humans, the pig has emerged as a highly suitable translational disease model, particularly for testing novel nutritional and technological interventions. Our goal was to develop a physiologically relevant porcine CD model to facilitate translation of findings and interventions towards the clinic.
METHODS
We generated pigs bearing a 93-bp deletion of the adenosine-uracil-rich element [ARE] and a constitutive-decay element within the 3' untranslated region of the TNF gene. Comparative analysis of physiological, molecular, histological and microbial characteristics was performed between wild-type, TNFΔARE/+ and TNFΔARE/ΔARE animals. Alterations in the microbiome were compared to the TNFΔARE mouse model and IBD patients.
RESULTS
TNF ΔARE pigs recapitulate major characteristics of human CD, including ulcerative transmural ileocolitis, increased abundance of proinflammatory cytokines, immune cell infiltration and dysbiotic microbial communities. 16S rRNA gene amplicon sequencing revealed enrichment in members belonging to Megasphaera, Campylobacter, Desulfovibrio, Alistipes and Lachnoclostridum in faecal or mucosa-associated bacteria compared to wild-type littermates. Principal components analysis clustering with a subset of TNFΔARE/+ mice and human IBD patients suggests microbial similarity based on disease severity.
CONCLUSIONS
We demonstrate that the TNFΔARE pig resembles a CD-like ileocolitis pathophenotype recapitulating human disease. The ability to conduct long-term studies and test novel surgical procedures and dietary interventions in a physiologically relevant model will benefit future translational IBD research studies.
Topics: Humans; Animals; Mice; Swine; Crohn Disease; RNA, Ribosomal, 16S; Tumor Necrosis Factor-alpha; Ileitis; Inflammatory Bowel Diseases
PubMed: 36821422
DOI: 10.1093/ecco-jcc/jjad034 -
Nutrients May 2023Changes in the composition and ratio of the flora during colitis have been found to potentially affect ovarian function through nutrient absorption. However, the...
Changes in the composition and ratio of the flora during colitis have been found to potentially affect ovarian function through nutrient absorption. However, the mechanisms have not been fully explored. To investigate whether colitis-induced dysbacteriosis of the intestinal flora affects ovarian function, mice were given dextran sodium sulfate (DSS) through drinking water. High-throughput sequencing technology was used to clarify the composition and proportion of bacterial flora as well as gene expression changes in the colon. Changes in follicle type, number, and hormone secretion in the ovary were detected. The results showed that 2.5% DSS could induce severe colitis symptoms, including increased inflammatory cell infiltration, severe damage to the crypt, and high expression of inflammatory factors. Moreover, vitamin A synthesis metabolism-related genes , , , , and were significantly decreased, as well as the levels of the steroid hormone synthase-related proteins STAR and CYP11A1. The levels of estradiol, progesterone, and Anti-Mullerian hormone as well as the quality of oocytes decreased significantly. The significantly changed abundances of , , , and some other flora had potentially important roles. DSS-induced colitis and impaired vitamin A absorption reduced ovarian function.
Topics: Female; Mice; Animals; Vitamin A; Dysbiosis; Gastrointestinal Microbiome; Colitis; Colon; Hormones; Dextran Sulfate; Mice, Inbred C57BL; Disease Models, Animal
PubMed: 37299390
DOI: 10.3390/nu15112425 -
GeroScience Apr 2024Microbiota composition has been linked to physical activity, health measures, and biological age, but a shared profile has yet to be shown. The aim of this study was to...
Microbiota composition has been linked to physical activity, health measures, and biological age, but a shared profile has yet to be shown. The aim of this study was to examine the associations between microbiota composition and measures of function, such as a composite measure of physical capacity, and biological age in midlife, prior to onset of age-related diseases. Seventy healthy midlife individuals (age 44.58 ± 0.18) were examined cross-sectionally, and their gut-microbiota profile was characterized from stool samples using 16SrRNA gene sequencing. Biological age was measured using the Klemera-Doubal method and a composition of blood and physiological biomarkers. Physical capacity was calculated based on sex-standardized functional tests. We demonstrate that the women had significantly richer microbiota, p = 0.025; however, microbiota diversity was not linked with chronological age, biological age, or physical capacity for either women or men. Men had slightly greater β-diversity; however, β-diversity was positively associated with biological age and with physical capacity for women only (p = 0.01 and p = 0.04; respectively). For women, an increase in abundance of Roseburia faecis and Collinsella aerofaciens, as well as genus Ruminococcus and Dorea, was significantly associated with higher biological age and lower physical capacity; an increase in abundance of Akkermansia muciniphila and genera Bacteroides and Alistipes was associated with younger biological age and increased physical capacity. Differentially abundant taxa were also associated with non-communicable diseases. These findings suggest that microbiota composition is a potential mechanism linking physical capacity and health status; personalized probiotics may serve as a new means to support health-promoting interventions in midlife. Investigating additional factors underlying this link may facilitate the development of a more accurate method to estimate the rate of aging.
Topics: Humans; Male; Female; Sex Characteristics; Gastrointestinal Microbiome; Exercise; Aging
PubMed: 37610596
DOI: 10.1007/s11357-023-00905-3 -
PloS One 2016Dysbiosis is a hallmark of inflammatory bowel disease (IBD), but it is unclear which specific intestinal bacteria predispose to and which protect from IBD and how they...
Dysbiosis is a hallmark of inflammatory bowel disease (IBD), but it is unclear which specific intestinal bacteria predispose to and which protect from IBD and how they are regulated. Peptidoglycan recognition proteins (Pglyrps) are antibacterial, participate in maintaining intestinal microflora, and modulate inflammatory responses. Mice deficient in any one of the four Pglyrp genes are more sensitive to dextran sulfate sodium (DSS)-induced colitis, and stools from Pglyrp-deficient mice transferred to wild type (WT) germ-free mice predispose them to much more severe colitis than stools from WT mice. However, the identities of these Pglyrp-regulated bacteria that predispose Pglyrp-deficient mice to colitis or protect WT mice from colitis are not known. Here we identified significant changes in β-diversity of stool bacteria in Pglyrp-deficient mice compared with WT mice. The most consistent changes in microbiome in all Pglyrp-deficient mice were in Bacteroidales, from which we selected four species, two with increased abundance (Prevotella falsenii and Parabacteroides distasonis) and two with decreased abundance (Bacteroides eggerthii and Alistipes finegoldii). We then gavaged WT mice with stock type strains of these species to test the hypothesis that they predispose to or protect from DSS-induced colitis. P. falsenii, P. distasonis, and B. eggerthii all enhanced DSS-induced colitis in both WT mice with otherwise undisturbed intestinal microflora and in WT mice with antibiotic-depleted intestinal microflora. By contrast, A. finegoldii (which is the most abundant species in WT mice) attenuated DSS-induced colitis both in WT mice with otherwise undisturbed intestinal microflora and in WT mice with antibiotic-depleted intestinal microflora, similar to the colitis protective effect of the entire normal microflora. These results identify P. falsenii, P. distasonis, and B. eggerthii as colitis-promoting species and A. finegoldii as colitis-protective species.
Topics: Animals; Bacteroidetes; Carrier Proteins; Colitis; Cytokines; Dextran Sulfate; Disease Susceptibility; Feces; Female; Gastrointestinal Microbiome; Immunity, Innate; Intestines; Mice; Mice, Inbred BALB C; Mice, Knockout; Prevotella; Probiotics; Ribotyping
PubMed: 26727498
DOI: 10.1371/journal.pone.0146162 -
Biochemistry and Biophysics Reports Sep 2023The acyl-acyl carrier protein synthetase enzyme enables some bacteria to scavenge free fatty acids from the environment for direct use in lipids. This fatty acid...
The acyl-acyl carrier protein synthetase enzyme enables some bacteria to scavenge free fatty acids from the environment for direct use in lipids. This fatty acid recycling pathway can help pathogens circumvent fatty acid synthase (FAS) inhibition with established antibiotics and those in clinical development. AasS enzymes are surprisingly hard to identify as they show high sequence similarity to other adenylate forming enzymes, and only a handful have been correctly annotated to date. Four recently discovered AasS enzymes from Gram negative bacteria, and , form distinct clusters in protein sequence similarity networks and have varying substrate preferences. We previously synthesized C10-AMS, an inhibitor of AasS that mimics the acyl-AMP reaction intermediate. Here we tested its ability to be broadly applicable to enzymes in this class, and found it inhibits all four newly annotated AasS enzymes. C10-AMS therefore provides a tool to study the role of AasS in fatty acid recycling in pathogenic bacteria as well as offers a platform for antibiotic development.
PubMed: 37771604
DOI: 10.1016/j.bbrep.2023.101549 -
PeerJ 2022Gut microbiota plays an important role in host health and is influenced by multiple factors. Hypobaric hypoxia usually existing at high altitude conditions can adversely...
BACKGROUND
Gut microbiota plays an important role in host health and is influenced by multiple factors. Hypobaric hypoxia usually existing at high altitude conditions can adversely affect normal physiological functions. However, the dynamic changes of gut microbiota influenced by hypobaric hypoxia have not been elucidated.
METHODS
In this study, we collected fecal samples from seven rats at 14 time points from entering the hypobaric chamber (eight time points) to leaving the chamber (six time points) and five rats served as normoxic controls. Metagenome sequencing was performed on all samples and the dynamics of taxa and functions were analyzed.
RESULTS
We found that the -diversity was changed in the first 5 days after entering or leaving the hypobaric chamber. The -diversity analysis revealed that gut microbiota structure was significantly separated among 14 time points. After entering the chamber, the relative abundance of decreased and the most abundant genus turned into . The abundance of Firmicutes and Bacteroidetes showed an opposite trend and both have a significant change within 5 days after entering or leaving the hypobaric hypoxia chamber. Some obligate anaerobic bacteria belonging to and were significantly enriched after entering the chamber for 5 weeks, whereas Probiotics like and , and short-chain fatty acids producers like and were significantly enriched after leaving the chamber for 3 weeks. Microbial functions like 'Two-component regulatory system', 'beta-carotene biosynthesis' and 'Fatty acid biosynthesis' were significantly enriched after entering the chamber for 5 weeks. Hypobaric hypoxia conditions could deeply affect the diversity and structure of gut microbiota. The alterations of abundance of dominant taxa ( and ), increased anaerobes and decreased probiotics induced by hypobaric hypoxia conditions might affect the host health.
Topics: Rats; Animals; Gastrointestinal Microbiome; Hypoxia; Feces; Bacteria, Anaerobic; Fatty Acids, Volatile
PubMed: 36225905
DOI: 10.7717/peerj.14090 -
Revista Espanola de Enfermedades... Nov 2015The human colonic mucosa is populated by a wide range of microorganisms, usually in a symbiotic relation with the host. Sometimes this balance is lost and a state of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIM
The human colonic mucosa is populated by a wide range of microorganisms, usually in a symbiotic relation with the host. Sometimes this balance is lost and a state of dysbiosis arises, exposing the colon to different metabolic and inflammatory stimuli (according to the microbiota's changing profile). Recent findings lead to hypothesize that this unbalance may create a subclinical pro-inflammatory state that increases DNA mutations and, therefore, colorectal carcinogenesis. In this article we aim to systematically review the scientific evidence regarding colonic microbiota and its role in colorectal carcinogenesis.
METHODS
Systematic review of PubMed searching results for original articles studying microbiota and colorectal cancer until November 2014.
RESULTS
Thirty-one original articles studied the role of colon microbiota in colorectal carcinoma including both human and animal studies. Different and heterogeneous methods were used and different bacteria were considered. Nevertheless, some bacteria are consistently augmented (such as Fusobacteria, Alistipes, Porphyromonadaceae, Coriobacteridae, Staphylococcaceae, Akkermansia spp. and Methanobacteriales), while other are constantly diminished in colorectal cancer (such as Bifidobacterium, Lactobacillus, Ruminococcus, Faecalibacterium spp., Roseburia, and Treponema). Moreover, bacteria metabolites amino acids are increased and butyrate is decreased throughout colonic carcinogenesis.
CONCLUSION
Conclusive evidence shows that colorectal carcinogenesis is associated with microbial dysbiosis. This information may be used to create new prophylactic, diagnostic and therapeutic strategies for colorectal cancer.
Topics: Animals; Carcinogenesis; Colon; Colorectal Neoplasms; Dysbiosis; Humans; Microbiota
PubMed: 26541655
DOI: 10.17235/reed.2015.3830/2015 -
Journal of Animal Science and... Sep 2023The poultry industry needs effective antibiotic alternatives to control outbreaks of necrotic enteritis (NE) caused by Clostridium perfringens.
BACKGROUND
The poultry industry needs effective antibiotic alternatives to control outbreaks of necrotic enteritis (NE) caused by Clostridium perfringens.
METHODS
The aim of this study was to investigate the effects of dietary supplementation with Macleaya cordata extract (MCE) on the immune function and gut microbiota of broilers with NE. A total of 288 1-day-old broiler chicks were randomly assigned to a 2 × 2 factorial arrangement with two concentrations of dietary MCE supplementation (0 or 350 mg/kg of diet) and two disease challenge statuses (control or NE).
RESULTS
The results revealed that NE significantly increased the feed conversion rate (FCR), mortality, intestinal lesion score, the levels of IL-1β, IL-17 and IFN-γ/IL-4 in serum and IL-17/IL-10 in the jejunal mucosa, mRNA levels of TLR2, IFN-γ and pIgR in the jejunum, and Clostridium perfringens concentrations in the cecum. NE significantly decreased the body weight (BW), body weight gain (BWG), jejunal villus height, V/C, mRNA level of AMPK-α1 in jejunum, IL-4 level in the jejunal mucosa and lactic acid bacteria abundance in the cecum. MCE significantly increased BW, BWG, jejunal villus height, V/C, mRNA levels of occludin, ZO-1 and AMPK-α1 in the jejunum, the levels of IgA and IgG in serum and IL-10 in the jejunal mucosa and mRNA levels of NF-κB, IL-10 and MHC-II in the jejunum. Additionally, MCE significantly decreased the FCR, mortality, intestinal lesion score, jejunal crypt depth, the levels of IFN-γ and IL-17 in serum and IL-17/IL-10 in the jejunal mucosa, Clostridium perfringens concentrations in the cecum, and mRNA levels of IL-17/IL-10 in the jejunum. Moreover, NE significantly increased the abundance of bacteria that are associated with inflammation, obesity and depression (Alistipes, Barnesiella, Intestinimonas, RF39 and UCG-005) and significantly decreased the abundance of short-chain fatty acid (SCFA)-producing bacteria (Anaerotruncus, Butyricicoccus and Bacteroides) in the cecum. MCE significantly increased the abundance of SCFA-producing bacteria (Streptococcus, Ruminococcus_torques_group and Lachnospiraceae_NK4A136_group) and significantly reduced the abundance of bacteria that are associated with inflammation and obesity (Alistipes, Barnesiella and UCG-010) in the cecum. In the cecum of broilers with NE, the relative abundance of Barnesiella and Alistipes was higher and that of Lachnoclostridium and Shuttleworthia was lower. Interestingly, these trends were reversed by the addition of MCE to the diet. Spearman correlation analysis showed that Barnesiella and Alistipes were associated with enhanced intestinal inflammation and inhibited growth performance, whereas Lachnoclostridium and Shuttleworthia were associated with anti-inflammatory effects.
CONCLUSIONS
MCE ameliorated the loss of growth performance in broiler chickens with NE, probably by regulating the intestinal barrier, immune function, and gut microbiota.
PubMed: 37674220
DOI: 10.1186/s40104-023-00916-2 -
Frontiers in Aging Neuroscience 2023The correlation between gut microbiota and Alzheimer's disease (AD) is increasingly being recognized by clinicians. However, knowledge about the gut-brain-cognition...
BACKGROUND
The correlation between gut microbiota and Alzheimer's disease (AD) is increasingly being recognized by clinicians. However, knowledge about the gut-brain-cognition interaction remains largely unknown.
METHODS
One hundred and twenty-seven participants, including 35 normal controls (NCs), 62 with subjective cognitive decline (SCD), and 30 with cognitive impairment (CI), were included in this study. The participants underwent neuropsychological assessments and fecal microbiota analysis through 16S ribosomal RNA (rRNA) Illumina Miseq sequencing technique. Structural MRI data were analyzed for cortical anatomical features, including thickness, sulcus depth, fractal dimension, and Toro's gyrification index using the SBM method. The association of altered gut microbiota among the three groups with structural MRI metrics and cognitive function was evaluated. Furthermore, co-expression network analysis was conducted to investigate the gut-brain-cognition interactions.
RESULTS
The abundance of , and decreased with cognitive ability. , and were specifically enriched in the CI group. abundance was correlated with changes in brain gray matter and cerebrospinal fluid volume ( = 0.0214, = 0.0162) and significantly with changes in cortical structures in brain regions, such as the internal olfactory area and the parahippocampal gyrus. The three colonies enriched in the CI group were positively correlated with cognitive function and significantly associated with changes in cortical structure related to cognitive function, such as the precuneus and syrinx gyrus.
CONCLUSION
This study provided evidence that there was an inner relationship among the altered gut microbiota, brain atrophy, and cognitive decline. Targeting the gut microbiota may be a novel therapeutic strategy for early AD.
PubMed: 37520126
DOI: 10.3389/fnagi.2023.1216509