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Renal Failure 2023Emerging evidence suggests that gut microbiota dysbiosis may play a critical role in the development of lupus nephritis (LN). However, the specific characteristics of... (Review)
Review
BACKGROUND
Emerging evidence suggests that gut microbiota dysbiosis may play a critical role in the development of lupus nephritis (LN). However, the specific characteristics of the gut microbiota in individuals with LN have not been fully clarified.
METHODS
The PubMed, Web of Science, and Embase databases were systematically searched for clinical and animal studies related to the relationship between LN and gut microbiota from inception until October 1, 2023. A semiquantitative analysis was used to assess the changes in gut microbial profiles.
RESULTS
A total of 15 clinical studies were selected for analysis, which included 138 LN patients, 441 systemic lupus erythematosus patients, and 1526 healthy controls (HCs). Five different types of LN mouse models were included in 5 animal studies. The alpha diversity was decreased in LN patients compared to HCs. A significant decrease in the (F/B) ratio is considered a hallmark of pathological conditions. Specifically, alterations in the abundance of the phylum , genera and and species and may play a critical role in the pathogenesis of LN. Remarkably, the gut taxonomic chain -- was enriched in LN patients, which could be a crucial characteristic of LN patients. The increased level of interleukin-6, imbalance of regulatory T cells and T helper 17 cells, and decreased level of the intestinal tight junction proteins zonula occludens-1 and claudin-1 also might be related to the pathogenesis of LN.
CONCLUSIONS
Specific changes in the abundance of gut microbiota such as decreased F/B ratio, and the level of inflammatory indicators, and markers of intestinal barrier dysfunction may play a crucial role in the pathogenesis of LN. These factors could be effective diagnostic and potential therapeutic targets for LN.
Topics: Animals; Mice; Humans; Lupus Nephritis; Gastrointestinal Microbiome; Lupus Erythematosus, Systemic; Intestinal Diseases; Interleukin-6
PubMed: 37994423
DOI: 10.1080/0886022X.2023.2285877 -
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 -
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 -
Frontiers in Immunology 2023Gut microbial imbalance (dysbiosis) has been reported in patients with acute Kawasaki disease (KD). However, no studies have analyzed the gut microbiota while focusing...
INTRODUCTION
Gut microbial imbalance (dysbiosis) has been reported in patients with acute Kawasaki disease (KD). However, no studies have analyzed the gut microbiota while focusing on susceptibility to KD. This study aimed to evaluate whether dysbiosis elevates susceptibility to KD by assessing children with a history of KD.
METHODS
Fecal DNA was extracted from 26 children with a history of KD approximately 1 year prior (KD group, 12 boys; median age, 32.5 months; median time from onset, 11.5 months) and 57 age-matched healthy controls (HC group, 35 boys; median age, 36.0 months). 16S rRNA gene analysis was conducted with the Illumina Miseq instrument. Sequence reads were analyzed using QIIME2.
RESULTS
For alpha diversity, Faith's phylogenetic diversity was significantly higher in the KD group. Regarding beta diversity, the two groups formed significantly different clusters based on Bray-Curtis dissimilarity. Comparing microbial composition at the genus level, the KD and HC groups were significantly different in the abundance of two genera with abundance over 1% after Benjamini-Hochberg false discovery rate correction for multiple comparisons. Compared with the HC group, the KD group had higher relative abundance of group and lower relative abundance of .
DISCUSSION AND CONCLUSION
group reportedly includes pro-inflammatory bacteria. In contrast, suppresses inflammation via butyrate production. In the predictive functional analysis, the proportion of gut microbiota involved in several pathways was lower in the KD group. Therefore, dysbiosis characterized by distinct microbial diversity and decreased abundance of in parallel with increased abundance of group might be a susceptibility factor for KD.
Topics: Male; Child; Humans; Child, Preschool; Gastrointestinal Microbiome; Dysbiosis; RNA, Ribosomal, 16S; Mucocutaneous Lymph Node Syndrome; Phylogeny; Acute Disease; Ruminococcus
PubMed: 38022552
DOI: 10.3389/fimmu.2023.1268453 -
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 -
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 -
Genes Oct 2020Relatively little is known about the ecological forces shaping the gut microbiota composition during infancy. Therefore, the objective of the present study was to...
Relatively little is known about the ecological forces shaping the gut microbiota composition during infancy. Therefore, the objective of the present study was to identify the nutrient utilization- and short-chain fatty acid (SCFA) production potential of gut microbes in infants during the first year of life. Stool samples were obtained from mothers at 18 weeks of pregnancy and from infants at birth (first stool) at 3, 6, and 12-months of age from the general population-based PreventADALL cohort. We identified the taxonomic and SCFA composition in 100 mother-child pairs. The SCFA production and substrate utilization potential of gut microbes were observed by multiomics (shotgun sequencing and proteomics) on six infants. We found a four-fold increase in relative butyrate levels from 6 to 12 months of infant age. The increase was correlated to and its bacterial network, and relative abundance, while low butyrate at 12 months was correlated to and its associated network of bacteria. Both and expressed enzymes needed for butyrate production and enzymes related to dietary fiber degradation, while expressed mucus-, fucose, and human milk oligosaccharides (HMO)-related degradation enzymes. Therefore, we believe that the presence of its network, and are key bacteria in the transition from an infant- to an adult-like gut microbiota with respect to butyrate production. Our results indicate that the transition from an infant- to an adult-like gut microbiota with respect to butyrate producing bacteria, occurs between 6 and 12 months of infant age. The bacteria associated with the increased butyrate ratio/levels were and , which potentially utilize a variety of dietary fibers based on the glycoside hydrolases (GHs) expressed. with a negative association to butyrate potentially utilizes mucin, fucose, and HMO components. This knowledge could have future importance in understanding how microbial metabolites can impact infant health and development.
Topics: Butyrates; Clostridiales; Coenzyme A-Transferases; Eubacterium; Fatty Acids, Volatile; Gastrointestinal Microbiome; Humans; Infant
PubMed: 33105702
DOI: 10.3390/genes11111245 -
Synthesis of the pentasaccharide repeating unit from and measurement of its inflammatory properties.RSC Advances Apr 2021The roles played by the gut microbiome in human health are increasingly recognized, and the prevalence of specific microorganisms has been correlated with different...
The roles played by the gut microbiome in human health are increasingly recognized, and the prevalence of specific microorganisms has been correlated with different diseases. For example, blooms of the Gram-positive bacterium have been correlated with inflammatory bowel disease, and recently a polysaccharide produced by this organism was shown to stimulate release of inflammatory cytokines. This stimulation was proposed to signal through toll-like receptor 4 (TLR4). We have synthesized the pentasaccharide repeating unit of this polysaccharide and showed that it stimulates TNF-α and IL-6 release from bone marrow-derived dendritic cells (BMDCs) in a TLR4-dependent manner. A related glycan does not stimulate significant cytokine release, demonstrating TLR4 selectivity in glycan recognition.
PubMed: 35424013
DOI: 10.1039/d1ra01918j -
Heliyon Sep 2023This study aims to investigate the changes in gut microbiota and metabolism of patients with chronic kidney disease (CKD) stage 1-2, as well as the potential impact of...
OBJECT
This study aims to investigate the changes in gut microbiota and metabolism of patients with chronic kidney disease (CKD) stage 1-2, as well as the potential impact of hyperuricemia (HUA) on these factors in CKD stage 1-2 patients.
METHODS
In this study, fecal samples were collected from CKD stage 1-2 without HUA patients (CKD-N group), CKD stage 1-2 with HUA patients (CKD-H group), and healthy people controls (HCs group). The samples were then subjected to the microbiome (16S rRNA gene sequencing) and metabolome (liquid chromatography-tandem mass spectrometry) analyses. The multi-omics datasets were analyzed individually and integrated for combined analysis using various bioinformatics approaches.
RESULTS
Gut microbial dysbiosis was found in CKD-N and CKD-H patients. At the phylum level, compared to HCs group, decreased but increased in CKD-H group significantly. in CKD-N group was significantly lower than HCs group. At genus level, , , and significantly changed in CKD groups. was significantly lower in CKD-H group than CKD-N group. Moreover, the fecal metabolome of CKD-N and CKD-H altered significantly. d-glutamine and d-glutamate metabolism, arginine and proline metabolism, histidine metabolism, and lysine biosynthesis were down-regulated in the CKD-N group. Phenylalanine metabolism, arginine and proline metabolism, purine metabolism, and beta-alanine metabolism were up-regulated in the CKD-H group. There was a significant difference between the two CKD groups in phenylalanine metabolism. The abundance change of , , , , and had a close correlation with differential metabolites.
CONCLUSION
The gut microbiota and metabolic status undergo significant changes in CKD patients compared to healthy people. Additionally, HUA has been found to impact the gut microbiota of CKD patients, as well as their metabolism. The close association between gut microbiota and metabolites suggests that the former plays a crucial role in metabolism.
PubMed: 37809388
DOI: 10.1016/j.heliyon.2023.e20328 -
Biomolecules Oct 2021Adhesion to the digestive mucosa is considered a key factor for bacterial persistence within the gut. In this study, we show that E1 can express the gene, which...
Adhesion to the digestive mucosa is considered a key factor for bacterial persistence within the gut. In this study, we show that E1 can express the gene, which encodes an adhesin of the MSCRAMMs family, only when it colonizes the gut. The RadA N-terminal region contains an all-β bacterial Ig-like domain known to interact with collagens. We observed that it preferentially binds human immunoglobulins (IgA and IgG) and intestinal mucins. Using deglycosylated substrates, we also showed that the RadA N-terminal region recognizes two different types of motifs, the protein backbone of human IgG and the glycan structure of mucins. Finally, competition assays with lectins and free monosaccharides identified Galactose and N-Acetyl-Galactosamine motifs as specific targets for the binding of RadA to mucins and the surface of human epithelial cells.
Topics: Clostridiales; Mucins; Polysaccharides; Symbiosis
PubMed: 34827611
DOI: 10.3390/biom11111613