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Nutrients Jul 2023The gut microbiota is a dynamic community of bacteria distributed in the gastroenteric tract and changes in response to diseases, diet, use of antibiotics and... (Review)
Review
The gut microbiota is a dynamic community of bacteria distributed in the gastroenteric tract and changes in response to diseases, diet, use of antibiotics and probiotics, hygiene status, and other environmental factors. Dysbiosis, a disruption of the normal crosstalk between the host and the microbes, is associated with obesity, diabetes, cancer, and cardiovascular diseases, is linked to a reduction of anti-inflammatory bacteria like and , and to an increase in the growth of proinflammatory species like and . Some plants possess anticancer properties and various studies have reported that some of these are also able to modulate the gut microbiota. The aim of this work is to evaluate the crucial relationship between medical plants and gut microbiota and the consequences on the onset and progression of cancer. In vivo studies about hematological malignancies showed that beta-glucans tie to endogenous antibeta glucan antibodies and to iC3b, an opsonic fragment of the central complement protein C3, leading to phagocytosis of antibody-targeted neoplastic cells and potentiation of the cytotoxic activity of the innate immune system if administered together with monoclonal antibodies. In conclusion, this review suggests the potential use of medical plants to improve gut dysbiosis and assist in the treatment of cancer.
Topics: Humans; Gastrointestinal Microbiome; Dysbiosis; Obesity; Bacteria; Diet; Neoplasms; Probiotics
PubMed: 37571264
DOI: 10.3390/nu15153327 -
Rheumatology and Immunology Research Dec 2023The gut microbiome represents a potential promising therapeutic target for autoimmune diseases. This review summarizes the current knowledge on the links between the gut...
The gut microbiome represents a potential promising therapeutic target for autoimmune diseases. This review summarizes the current knowledge on the links between the gut microbiome and several autoimmune rheumatic diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) spondyloarthropathies (SpA), Sjogren's syndrome (SS), and systemic sclerosis (SSc). Evidence from studies of RA and SLE patients suggests that alterations in the gut microbiome composition and function contribute to disease development and progression through increased gut permeability, with microbes and microbial metabolites driving an excessive systemic activation of the immune system. Also, there is growing evidence that gut dysbiosis and subsequent immune cell activation may contribute to disease pathogenesis in SpA and SS. For SSc, there are fewer, but these are still informative, reports on alterations in the gut microbiome. In general, the complex interplay between the microbiome and the immune system is still not fully understood. Here we discuss the current knowledge of the link between the gut microbiome and autoimmune rheumatic diseases, highlighting potentially fertile areas for future research and make considerations on the potential benefits of strategies that restore gut microbiome homeostasis.
PubMed: 38125641
DOI: 10.2478/rir-2023-0027 -
Scientific Reports Nov 2022Moyamoya disease (MMD) is a rare cerebrovascular disease endemic in East Asia. The p.R4810K mutation in RNF213 gene confers a risk of MMD, but other factors remain...
Moyamoya disease (MMD) is a rare cerebrovascular disease endemic in East Asia. The p.R4810K mutation in RNF213 gene confers a risk of MMD, but other factors remain largely unknown. We tested the association of gut microbiota with MMD. Fecal samples were collected from 27 patients with MMD, 7 patients with non-moyamoya intracranial large artery disease (ICAD) and 15 control individuals with other disorders, and 16S rRNA were sequenced. Although there was no difference in alpha diversity or beta diversity between patients with MMD and controls, the cladogram showed Streptococcaceae was enriched in patient samples. The relative abundance analysis demonstrated that 23 species were differentially abundant between patients with MMD and controls. Among them, increased abundance of Ruminococcus gnavus > 0.003 and decreased abundance of Roseburia inulinivorans < 0.002 were associated with higher risks of MMD (odds ratio 9.6, P = 0.0024; odds ratio 11.1, P = 0.0051). Also, Ruminococcus gnavus was more abundant and Roseburia inulinivorans was less abundant in patients with ICAD than controls (P = 0.046, P = 0.012). The relative abundance of Ruminococcus gnavus or Roseburia inulinivorans was not different between the p.R4810K mutant and wildtype. Our data demonstrated that gut microbiota was associated with both MMD and ICAD.
Topics: Humans; Moyamoya Disease; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Ruminococcus; Intracranial Arterial Diseases; Rare Diseases; Arteries; Adenosine Triphosphatases; Ubiquitin-Protein Ligases
PubMed: 36424438
DOI: 10.1038/s41598-022-24496-9 -
Microbiome May 2023The gut microbiota is implicated in the pathogenesis of colorectal cancer (CRC). We aimed to map the CRC mucosal microbiota and metabolome and define the influence of... (Observational Study)
Observational Study
BACKGROUND AND AIMS
The gut microbiota is implicated in the pathogenesis of colorectal cancer (CRC). We aimed to map the CRC mucosal microbiota and metabolome and define the influence of the tumoral microbiota on oncological outcomes.
METHODS
A multicentre, prospective observational study was conducted of CRC patients undergoing primary surgical resection in the UK (n = 74) and Czech Republic (n = 61). Analysis was performed using metataxonomics, ultra-performance liquid chromatography-mass spectrometry (UPLC-MS), targeted bacterial qPCR and tumour exome sequencing. Hierarchical clustering accounting for clinical and oncological covariates was performed to identify clusters of bacteria and metabolites linked to CRC. Cox proportional hazards regression was used to ascertain clusters associated with disease-free survival over median follow-up of 50 months.
RESULTS
Thirteen mucosal microbiota clusters were identified, of which five were significantly different between tumour and paired normal mucosa. Cluster 7, containing the pathobionts Fusobacterium nucleatum and Granulicatella adiacens, was strongly associated with CRC (P = 0.0002). Additionally, tumoral dominance of cluster 7 independently predicted favourable disease-free survival (adjusted p = 0.031). Cluster 1, containing Faecalibacterium prausnitzii and Ruminococcus gnavus, was negatively associated with cancer (P = 0.0009), and abundance was independently predictive of worse disease-free survival (adjusted p = 0.0009). UPLC-MS analysis revealed two major metabolic (Met) clusters. Met 1, composed of medium chain (MCFA), long-chain (LCFA) and very long-chain (VLCFA) fatty acid species, ceramides and lysophospholipids, was negatively associated with CRC (P = 2.61 × 10); Met 2, composed of phosphatidylcholine species, nucleosides and amino acids, was strongly associated with CRC (P = 1.30 × 10), but metabolite clusters were not associated with disease-free survival (p = 0.358). An association was identified between Met 1 and DNA mismatch-repair deficiency (p = 0.005). FBXW7 mutations were only found in cancers predominant in microbiota cluster 7.
CONCLUSIONS
Networks of pathobionts in the tumour mucosal niche are associated with tumour mutation and metabolic subtypes and predict favourable outcome following CRC resection. Video Abstract.
Topics: Humans; Chromatography, Liquid; Tandem Mass Spectrometry; Microbiota; Gastrointestinal Microbiome; Colorectal Neoplasms
PubMed: 37158960
DOI: 10.1186/s40168-023-01518-w -
The Lancet. Diabetes & Endocrinology Jul 2022
Topics: Clostridiales; Cross-Sectional Studies; Gastrointestinal Microbiome; Humans; Metabolic Syndrome; Ruminococcus
PubMed: 35662399
DOI: 10.1016/S2213-8587(22)00113-9 -
Journal of Microbiology and... Mar 2024In this study, we aim to investigate the precise alterations in the gut microbiota during the onset and advancement of diabetic nephropathy (DN) and examine the impact...
In this study, we aim to investigate the precise alterations in the gut microbiota during the onset and advancement of diabetic nephropathy (DN) and examine the impact of () on DN. Eight-week-old male KK-Ay mice were administered antibiotic cocktails for a duration of two weeks, followed by oral administration of for an additional eight weeks. Our study revealed significant changes in the gut microbiota during both the initiation and progression of DN. Specifically, we observed a notable increase in the abundance of Clostridia at the class level, higher levels of Lachnospirales and Oscillospirales at the order level, and a marked decrease in Clostridia_UCG-014 in DN group. Additionally, there was a significant increase in the abundance of Lachnospiraceae, Oscillospiraceae, and Ruminococcaceae at the family level. Moreover, oral administration of effectively aggravated kidney pathology in DN mice, accompanied by elevated levels of urea nitrogen (UN), creatinine (Cr), and urine protein. Furthermore, administration resulted in down-regulation of tight junction proteins such as Claudin-1, Occludin, and ZO-1, as well as increased levels of uremic toxins in urine and serum samples. Additionally, our study demonstrated that orally administered up-regulated the expression of inflammatory factors, including nucleotide-binding oligomerization domain-like receptor pyrin domain-containing protein 3 (NLRP3) and Interleukin (IL)-6. These changes indicated the involvement of the gut-kidney axis in DN, and may worsen diabetic nephropathy by affecting uremic toxin levels and promoting inflammation in DN.
Topics: Mice; Male; Animals; Diabetic Nephropathies; Ruminococcus; Gastrointestinal Microbiome; Clostridiales; Diabetes Mellitus
PubMed: 38346799
DOI: 10.4014/jmb.2310.10028 -
Cellular and Molecular Life Sciences :... Jan 2021The availability and repartition of fucosylated glycans within the gastrointestinal tract contributes to the adaptation of gut bacteria species to ecological niches. To...
The availability and repartition of fucosylated glycans within the gastrointestinal tract contributes to the adaptation of gut bacteria species to ecological niches. To access this source of nutrients, gut bacteria encode α-L-fucosidases (fucosidases) which catalyze the hydrolysis of terminal α-L-fucosidic linkages. We determined the substrate and linkage specificities of fucosidases from the human gut symbiont Ruminococcus gnavus. Sequence similarity network identified strain-specific fucosidases in R. gnavus ATCC 29149 and E1 strains that were further validated enzymatically against a range of defined oligosaccharides and glycoconjugates. Using a combination of glycan microarrays, mass spectrometry, isothermal titration calorimetry, crystallographic and saturation transfer difference NMR approaches, we identified a fucosidase with the capacity to recognize sialic acid-terminated fucosylated glycans (sialyl Lewis X/A epitopes) and hydrolyze α1-3/4 fucosyl linkages in these substrates without the need to remove sialic acid. Molecular dynamics simulation and docking showed that 3'-Sialyl Lewis X (sLeX) could be accommodated within the binding site of the enzyme. This specificity may contribute to the adaptation of R. gnavus strains to the infant and adult gut and has potential applications in diagnostic glycomic assays for diabetes and certain cancers.
Topics: Bacterial Proteins; Clostridiales; Gastrointestinal Microbiome; Gastrointestinal Tract; Glycoconjugates; Humans; Oligosaccharides; Polysaccharides; Substrate Specificity; alpha-L-Fucosidase
PubMed: 32333083
DOI: 10.1007/s00018-020-03514-x -
Frontiers in Immunology 2022Imbalances in the gut microbiome are suspected contributors to the pathogenesis of Systemic Lupus Erythematosus, and our studies and others have documented that patients...
Imbalances in the gut microbiome are suspected contributors to the pathogenesis of Systemic Lupus Erythematosus, and our studies and others have documented that patients with active Lupus nephritis have expansions of the obligate anaerobe, (RG). To investigate whether the RG strains in Lupus patients have pathogenic properties in a gnotobiotic system, we colonized C57BL/6 mice with individual RG strains from healthy adults or those from Lupus patients. These strains were similar in their capacity for murine intestinal colonization of antibiotic-preconditioned specific-pathogen-free, as well as of germ-free adults and of their neonatally colonized litters. Lupus-derived RG strains induced high levels of intestinal permeability that was significantly greater in female than male mice, whereas the RG species-type strain (ATCC29149/VPI C7-1) from a healthy donor had little or no effects. These Lupus RG strain-induced functional alterations were associated with RG translocation to mesenteric lymph nodes, and raised serum levels of zonulin, a regulator of tight junction formation between cells that form the gut barrier. Notably, the level of Lupus RG-induced intestinal permeability was significantly correlated with serum IgG anti RG cell-wall lipoglycan antibodies, and with anti-native DNA autoantibodies that are a biomarker for SLE. Strikingly, gut permeability was completely reversed by oral treatment with larazotide acetate, an octapeptide that is a specific molecular antagonist of zonulin. Taken together, these studies document a pathway by which RG strains from Lupus patients contribute to a leaky gut and features of autoimmunity implicated in the pathogenesis of flares of clinical Lupus disease.
Topics: Animals; Antibodies, Antinuclear; Autoimmunity; Clostridiales; Female; Gastrointestinal Microbiome; Haptoglobins; Humans; Lupus Erythematosus, Systemic; Male; Mice; Mice, Inbred C57BL; Permeability; Protein Precursors; Ruminococcus; Sex Factors
PubMed: 36032126
DOI: 10.3389/fimmu.2022.897971 -
Frontiers in Immunology 2023Tuft cells are a type of rare epithelial cells that have been recently found to utilize taste signal transduction pathways to detect and respond to various noxious...
Tuft cells are a type of rare epithelial cells that have been recently found to utilize taste signal transduction pathways to detect and respond to various noxious stimuli and pathogens, including allergens, bacteria, protists and parasitic helminths. It is, however, not fully understood how many different types of pathogens they can sense or what exact molecular mechanisms they employ to initiate targeted responses. In this study, we found that an anaerobic pathobiont microbe, (), can induce tuft cell proliferation in the proximal colon whereas the microbe's lysate can stimulate these proximal colonic tuft cells to release interleukin-25 (IL-25). Nullification of the and genes that encode the G protein subunit Gγ13 and transient receptor potential ion channel Trpm5, respectively, or application of the Tas2r inhibitor allyl isothiocyanate (AITC), G protein Gβγ subunit inhibitor Gallein or the phospholipase Cβ2 (PLCβ2) inhibitor U73122 reduces -elicited tuft cell proliferation or IL-25 release or both. Furthermore, conditional knockout or knockout diminishes the expression of gasdermins C2, C3 and C4, and concomitantly increases the activated forms of caspases 3, 8 and 9 as well as the number of TUNEL-positive apoptotic cells in the proximal colon. Together, our data suggest that taste signal transduction pathways are not only involved in the detection of infection, but also contribute to helping maintain gasdermin expression and prevent apoptotic cell death in the proximal colon, and these findings provide another strategy to combat infection and sheds light on new roles of taste signaling proteins along with gasdermins in protecting the integrity of the proximal colonic epithelium.
Topics: Taste; Ruminococcus; Signal Transduction; Transient Receptor Potential Channels; Colon
PubMed: 37954611
DOI: 10.3389/fimmu.2023.1259521 -
Renal Failure Dec 2023Vascular calcification (VC) is an independent risk factor for cardiovascular mortality in end-stage renal disease (ESRD) patients. The pathogenesis of VC is complicated...
INTRODUCTION
Vascular calcification (VC) is an independent risk factor for cardiovascular mortality in end-stage renal disease (ESRD) patients. The pathogenesis of VC is complicated and unclear. Uremic toxins produced by gut microbiota can promote VC. This study aims to identify the differences in gut microbiota between the different VC groups and the main bacteria associated with VC in hemodialysis (HD) patients in an attempt to open up new preventive and therapeutic approaches and define the probable mechanism for VC in HD patients in the future.
METHODS
A total of 73 maintenance HD patients were enrolled in this cross-sectional study. According to the abdominal aortic calcification (AAC) scores, the participants were divided into the high AAC score group and the low AAC score group. High-throughput sequencing of the gut microbiota was performed and the results were evaluated by alpha diversity, beta diversity, species correlation, and model predictive analyses.
RESULTS
The prevalence of VC was 54.79% (40/73) in the study. The majority of phyla in the two groups were the same, including , , , and . The microbial diversity in the high AAC score group had a decreasing trend ( = 0.050), and the species abundance was significantly lower ( = 0.044) than that in the low AAC score group. The HD patients with high AAC scores showed an increased abundance of and decreased abundances of and at the phylum level; increased abundances of and and decreased abundances of and at the genus level (0.05). and were positively correlated with VC, and , and were negatively correlated with VC. had the greatest influence on VC in HD patients, followed by and
CONCLUSIONS
Our results provide clinical evidence that there was a difference in gut microbiota between the different VC groups in HD patients. a lipopolysaccharide (LPS)-producing bacterium, was positively correlated with VC and had the greatest influence on VC. a short-chain fatty acid (SCFA)-producing bacterium, was negatively correlated with VC and had the second strongest influence on VC in HD patients. The underlying mechanism is worth studying. These findings hint at a new therapeutic target.
Topics: Humans; Gastrointestinal Microbiome; Cross-Sectional Studies; Renal Dialysis; Kidney Failure, Chronic; Vascular Calcification; Bacteria
PubMed: 36632746
DOI: 10.1080/0886022X.2022.2148538