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Gut Microbes 2024Comensal () and are often linked to gut inflammation. However, the causes for variability of pro-inflammatory surface antigens that affect gut commensal/opportunistic...
Comensal () and are often linked to gut inflammation. However, the causes for variability of pro-inflammatory surface antigens that affect gut commensal/opportunistic dualism in remain unclear. By using the classical lipopolysaccharide/O-antigen ' operon' in as a surface antigen model (5-gene-cluster ), and a recent typing strategy for strain classification, we characterized the integrity and conservancy of the entire operon in . Through exploratory analysis of complete genomes and metagenomes, we discovered that most have the operon fragmented into nonrandom patterns of gene-singlets and doublets/triplets, termed 'gene-clusters', or rfb-'minioperons' if predicted as transcriptional. To reflect global operon integrity, contiguity, duplication, and fragmentation principles, we propose a six-category (infra/supra-numerary) cataloging system and a Global Operon Profiling System for bacteria. Mechanistically, genomic sequence analyses revealed that operon fragmentation is driven by intra-operon insertions of predominantly -DNA () and likely natural selection in gut-wall specific micro-niches or micropathologies. -insertions, also detected in other antigenic operons (fimbriae), but not in operons deemed essential (ribosomal), could explain why have fewer KEGG-pathways despite large genomes. DNA insertions, overrepresenting DNA-exchange-avid () species, impact our interpretation of functional metagenomics data by inflating by inflating gene-based pathway inference and by overestimating 'extra-species' abundance. Of disease relevance, species isolated from cavitating/cavernous fistulous tract (CavFT) microlesions in Crohn's Disease have supra-numerary fragmented operons, stimulate TNF-alpha from macrophages with low potency, and do not induce hyperacute peritonitis in mice compared to CavFT . The impact of 'foreign-DNA' insertions on pro-inflammatory operons, metagenomics, and commensalism/opportunism requires further studies to elucidate their potential for novel diagnostics and therapeutics, and to elucidate the role of co-existing pathobionts in Crohn's disease microlesions.
Topics: Operon; Mice; Gastrointestinal Microbiome; Animals; Humans; Metagenomics; Crohn Disease; Bacteroidetes; Antigens, Bacterial; Genome, Bacterial; Enterobacteriaceae
PubMed: 38841888
DOI: 10.1080/19490976.2024.2350150 -
Frontiers in Nutrition 2024The intricate interplay between dietary habits and the development of Parkinson's Disease (PD) has long been a subject of scientific inquiry. Mendelian Randomization...
BACKGROUND
The intricate interplay between dietary habits and the development of Parkinson's Disease (PD) has long been a subject of scientific inquiry. Mendelian Randomization (MR) emerges as a potent tool, harnessing genetic variants to infer causality in observational data. While evidence links diet to Parkinson's Disease (PD) etiology, a thorough MR exploration of dietary impacts on PD, particularly involving gut microbiota, is still emerging.
METHODS
This research leverages the IEU Open GWAS project's vast GWAS database to address the knowledge gap in understanding diet's influence on PD, employing a diverse range of dietary variables. Our holistic dataset includes various foods like processed fava beans, bap, red wine, to cheese, reflecting a commitment to untangling dietary complexities in PD etiology. Advancing from initial dietary-PD associations, we innovatively explore the gut microbiota, focusing on in relation to bap intake and PD, employing MR. Utilizing weighted median, MR-Egger, and inverse variance weighting methods, we ensure rigorous causality assessments, meticulously mitigating pleiotropy and heterogeneity biases to uphold finding validity.
RESULTS
Our findings indicate red wine (OR: 1.031; 95% CI 1.001-1.062; = 0.044) and dried fruit consumption (OR: 2.019; 95% CI 1.052-3.875; = 0.035) correlate with increased PD risk, whereas broad beans (OR: 0.967; 95% CI 0.939-0.996; = 0.024) and bap intake (OR: 0.922; 95% CI 0.860-0.989; = 0.023) show protective effects against PD. Employing MR, specifically the IVW method, revealed a significant inverse association between bap intake and gut microbiota, marked by an 8.010-fold decrease in per standard deviation increase in bap intake (95% CI 1.005-63.818, = 0.049). Furthermore, a connection between PD and was observed (OR: 0.810; 95% CI 0.768-0.999; = 0.049), suggesting a potential microbiota-mediated pathway in PD etiology.
CONCLUSION
Our study links dietary habits to PD risk, showing higher PD risk with red wine and dried fruit consumption, and a protective effect from broad beans and bap. Using MR, we found bap intake inversely correlates with in the gut, suggesting bap influences microbiota. Further, higher levels correlate with lower PD risk, highlighting a complex interplay of diet, gut microbiome, and neurological health. These insights shed light on potential dietary interventions for PD.
PubMed: 38840699
DOI: 10.3389/fnut.2024.1273874 -
Frontiers in Nutrition 2024Chondroitin sulfate (CS) is a sulfated linear polysaccharide with different functional activities, including antioxidant, anti-inflammatory, lipid-lowering, and immune...
Intervention effects of low-molecular-weight chondroitin sulfate from the nasal cartilage of yellow cattle on lipopolysaccharide-induced behavioral disorders: regulation of the microbiome-gut-brain axis.
Chondroitin sulfate (CS) is a sulfated linear polysaccharide with different functional activities, including antioxidant, anti-inflammatory, lipid-lowering, and immune regulation. As natural sulfated polysaccharides have high molecular weight, high apparent viscosity, low water solubility, complex structure, and high negative charge, they have difficulty binding to receptors within cells across tissue barriers, resulting in low bioavailability and unclear structure-activity relationships. In this study, an HO-Vc oxidative degradation system was employed to perform environmentally friendly and controllable degradation of CS extracted from the nasal cartilage of Shaanxi Yellow cattle. Two low-molecular-weight chondroitin sulfates (LMWCSs), CS-1 (14.8 kDa) and CS-2 (50.9 kDa), that exhibit strong free radical scavenging ability were obtained, and their structures were characterized. Mice intraperitoneally administered lipopolysaccharide (LPS) were used to explore the cognitive intervention effects of LMWCS. Supplementing CS-1 and CS-2 significantly downregulated the levels of the serum inflammatory factors, TNF-α and IL-1β, promoted the expression of GSH in the brain, and inhibited the production of the lipid peroxidation product, malondialdehyde (MDA), ultimately inhibiting LPS-induced cognitive impairment in mice. Surprisingly, compared to the LPS model group, the abundances of , , , , and were significantly increased in the intestines of mice in the CS-1 and CS-2 group, whereas those of and were significantly decreased. Altogether, this study provides a theoretical basis for the comprehensive utilization of agricultural and animal resources and the application of brain nutrition, anti-inflammatory, and LMWCS health products.
PubMed: 38835960
DOI: 10.3389/fnut.2024.1371691 -
Frontiers in Microbiology 2024To examine the effects of an intervention with fructooligosaccharides (FOS), , and their combination in a mouse model of colitis and to explore the mechanisms underlying...
OBJECTIVE
To examine the effects of an intervention with fructooligosaccharides (FOS), , and their combination in a mouse model of colitis and to explore the mechanisms underlying these effects.
METHODS
The effects of FOS, , and their combination were evaluated in a DSS-induced mouse model of colitis. To this end, parameters such as body weight, the disease activity index (DAI), and colon length were examined in model mice. Subsequently, ELISA was employed to detect the serum levels of proinflammatory cytokines. Histopathological analysis was performed to estimate the progression of inflammation in the colon. Gas chromatography was used to determine the content of short-chain fatty acids (SCFAs) in the feces of model mice. Finally, 16S rRNA sequencing technology was used to analyze the gut microbiota composition.
RESULTS
FOS was slight effective in treating colitis and colitis-induced intestinal dysbiosis in mice. Meanwhile, could significantly reduced the DAI, inhibited the production of IL-1β, and prevented colon shortening. Nevertheless, treatment alone failed to effectively regulate the gut microbiota. In contrast, the combined administration of FOS/ resulted in better anti-inflammatory effects and enabled microbiota regulation. The FOS/ combination (10 CFU/ml and 10 CFU/ml) significantly reduced the DAI, inhibited colitis, lowered IL-1β and TNF-α production, and significantly improved the levels of butyric acid and isobutyric acid. However, FOS/ 10 CFU/ml exerted stronger anti-inflammatory effects, inhibited IL-6 production and attenuated colon shortening. Meanwhile, FOS/ 10 CFU/ml improved microbial regulation and alleviated the colitis-induced decrease in microbial diversity. The combination of FOS and significantly increased the abundance of and decreased the abundance of . Additionally, it promoted the production of acetic acid and propionic acid.
CONCLUSION
Compared with single administration, the combination can significantly increase the abundance of beneficial bacteria such as and and effectively regulate the gut microbiota composition. These results provide a scientific rationale for the prevention and treatment of colitis using a FOS/ combination. They also offer a theoretical basis for the development of nutraceutical preparations containing FOS and .
PubMed: 38835484
DOI: 10.3389/fmicb.2024.1356365 -
Drug Design, Development and Therapy 2024Given the potent immunostimulatory effects of bacterial outer membrane vesicles (OMVs) and the significant anti-colon tumor properties of (), this study aimed to...
PURPOSE
Given the potent immunostimulatory effects of bacterial outer membrane vesicles (OMVs) and the significant anti-colon tumor properties of (), this study aimed to elucidate the role and potential mechanisms of -derived OMVs (-OMVs) against colon cancer.
METHODS
This study isolated and purified -OMVs from cultures and assessed their characteristics. The effects of -OMVs on CT26 cell uptake, proliferation, and invasion were investigated in vitro. In vivo, a CT26 colon tumor model was used to investigate the anti-colon tumor effects and underlying mechanisms of -OMVs. Finally, we evaluated the biosafety of -OMVs.
RESULTS
Purified -OMVs had a uniform cup-shaped structure with an average size of 165.5 nm and a zeta potential of approximately -9.56 mV, and their proteins were associated with pathways related to immunity and apoptosis. In vitro experiments demonstrated that CT26 cells internalized the -OMVs, resulting in a significant decrease in their proliferation and invasion abilities. Further in vivo studies confirmed the accumulation of -OMVs in tumor tissues, which significantly inhibited the growth of colon tumors. Mechanistically, -OMVs increased the expression of CXCL10, promoting infiltration of CD8 T cells into tumor tissues and expression of pro-inflammatory factors TNF-α, IL-1β, and IL-6. Notably, -OMVs demonstrated a high level of biosafety.
CONCLUSION
This paper elucidates that -OMVs can exert significant anti-colon tumor effects by upregulating the expression of the chemokine CXCL10, thereby increasing the infiltration of CD8 T cells into tumors and enhancing antitumor immune responses. This suggests that -OMVs may be developed as a novel nanoscale potent immunostimulant with great potential for application in tumor immunotherapy. As well as developed as a novel nano-delivery carrier for combination with other antitumor drugs.
Topics: Colonic Neoplasms; Animals; CD8-Positive T-Lymphocytes; Mice; Cell Proliferation; Chemokine CXCL10; Mice, Inbred BALB C; Bacterial Outer Membrane; Antineoplastic Agents; Humans; Neoplasms, Experimental; Drug Screening Assays, Antitumor; Tumor Cells, Cultured
PubMed: 38828018
DOI: 10.2147/DDDT.S457338 -
Cell Reports May 2024Interleukin (IL)-22 promotes host-microbiota homeostasis. We sought to identify microbiota metabolite(s) that drive intestinal IL-22 production. We observed that...
Interleukin (IL)-22 promotes host-microbiota homeostasis. We sought to identify microbiota metabolite(s) that drive intestinal IL-22 production. We observed that exposing Peyer's patch cells (PPCs), ex vivo, to fecal supernatants (FSs) recapitulates fermentable fiber- and microbiota-dependent IL-22 production, and cellular sources thereof, thus supporting the use of this model. An interrogation of FSs generated from mice fed the fermentable fiber inulin (FS-Inu) revealed that its IL-22-inducing activity is mediated by heat-labile protein. Fractionation of FS-Inu by ion-exchange chromatography, and subsequent proteomic analysis of IL-22-inducing fractions, indicates that outer membrane protein A (OmpA) might be a microbial driver of IL-22 expression. Concomitantly, recombinant OmpA from Parabacteroides goldsteinii, which is enriched by an inulin diet, induces IL-22 production and expression of the IL-22-dependent genes REG3γ and -β, in PPCs and mice. Thus, OmpA is one bacterial inducer of IL-22 expression, potentially linking diet, mucosal immune homeostasis, and gut health.
PubMed: 38823020
DOI: 10.1016/j.celrep.2024.114292 -
World Journal of Hepatology May 2024Metabolic-dysfunction associated steatotic liver disease (MASLD) is a hepatic manifestation of metabolic syndrome. Studies suggest ornithine aspartate (LOLA) as drug...
BACKGROUND
Metabolic-dysfunction associated steatotic liver disease (MASLD) is a hepatic manifestation of metabolic syndrome. Studies suggest ornithine aspartate (LOLA) as drug therapy.
AIM
To analyze the influence of LOLA intake on gut microbiota using a nutritional model of MASLD.
METHODS
Adult male Sprague Dawley rats were randomized into three groups: Control (10 rats fed with a standard diet), MASLD (10 rats fed with a high-fat and choline-deficient diet), and LOLA (10 rats receiving 200 mg/kg/d LOLA, after the 16 week receiving high-fat and choline-deficient diet). After 28 wk of the experiment, animals were euthanized, and feces present in the intestine were collected. Following fecal DNA extraction, the V4 region of the 16S rRNA gene was amplified followed by sequencing in an Ion S5™ system.
RESULTS
Alpha and beta diversity metrics were comparable between MASLD and LOLA. 3 OTUs were differentially abundant between MASLD and LOLA, which belong to the species , , and . The functional prediction provided two different metabolic profiles between MASLD and LOLA. The 9 pathways differentially abundant in MASLD are related to a change in energy source, adenosine/purine nucleotides degradation as well as guanosine and adenosine deoxyribonucleotides biosynthesis. The 14 pathways differentially abundant in LOLA are associated with four major metabolic functions primarily influenced by L-aspartate, including tricarboxylic acid cycle pathways, purine/guanosine nucleotides biosynthesis, pyrimidine ribonucleotides biosynthesis and salvage as well as lipid IVA biosynthesis.
CONCLUSION
Although LOLA had no influence on alpha and beta diversity in this nutritional model of MASLD, it was associated with changes in specific gut microbes and their related metabolic pathways.
PubMed: 38818297
DOI: 10.4254/wjh.v16.i5.832 -
Frontiers in Cellular and Infection... 2024To investigate the structure, composition, and functions of the gut microbiota in elderly patients with hyperlipidemia.
OBJECTIVE
To investigate the structure, composition, and functions of the gut microbiota in elderly patients with hyperlipidemia.
METHODS
Sixteen older patients diagnosed with hyperlipidemia (M group) and 10 healthy, age-matched normal volunteers (N group) were included. These groups were further subdivided by sex into the male normal (NM, n = 5), female normal (NF, n = 5), male hyperlipidemia (MM, n = 8), and female hyperlipidemia (MF, n = 8) subgroups. Stool samples were collected for high-throughput sequencing of 16S rRNA genes. Blood samples were collected for clinical biochemical index testing.
RESULTS
Alpha- and beta-diversity analyses revealed that the structure and composition of the gut microbiota were significantly different between the M and N groups. The relative abundances of , , , , and were significantly decreased, while those of , , and were significantly higher in the M group. There were also significant sex-related differences in microbial structure between the NM and NF groups, and between the MM and MF groups. Through functional prediction with PICRUSt 2, we observed distinct between-group variations in metabolic pathways associated with the gut microbiota and their impact on the functionality of the nervous system. Pearson's correlation coefficient was used as a distance metric to build co-abundance networks. A hypergeometric test was used to detect taxonomies with significant enrichment in specific clusters. We speculated that modules with and as the core microbes play an important ecological role in the intestinal microbiota of the M group. The relative intestinal abundances of and in the M group were positively correlated with serum triglyceride and low-density lipoprotein levels, while the relative abundance of was negatively correlated with the serum lipoprotein a level.
Topics: Humans; Gastrointestinal Microbiome; Male; Female; Aged; Hyperlipidemias; RNA, Ribosomal, 16S; Feces; Bacteria; High-Throughput Nucleotide Sequencing; Middle Aged; Aged, 80 and over
PubMed: 38812752
DOI: 10.3389/fcimb.2024.1333145 -
New Microbes and New Infections Jun 2024
PubMed: 38799946
DOI: 10.1016/j.nmni.2024.101374 -
New Microbes and New Infections Jun 2024
PubMed: 38799907
DOI: 10.1016/j.nmni.2024.101373