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Scientific Reports Nov 2023Gastrointestinal symptoms are more prevalent in children with autism spectrum disorder (ASD) than in typically developing (TD) children. Constipation is a significant... (Clinical Trial)
Clinical Trial
Gastrointestinal symptoms are more prevalent in children with autism spectrum disorder (ASD) than in typically developing (TD) children. Constipation is a significant gastrointestinal comorbidity of ASD, but the associations among constipated autism spectrum disorder (C-ASD), microbiota and short-chain fatty acids (SCFAs) are still debated. We enrolled 80 children, divided into the C-ASD group (n = 40) and the TD group (n = 40). In this study, an integrated 16S rRNA gene sequencing and gas chromatography-mass spectrometry-based metabolomics approach was applied to explore the association of the gut microbiota and SCFAs in C-ASD children in China. The community diversity estimated by the Observe, Chao1, and ACE indices was significantly lower in the C-ASD group than in the TD group. We observed that Ruminococcaceae_UCG_002, Erysipelotrichaceae_UCG_003, Phascolarctobacterium, Megamonas, Ruminiclostridium_5, Parabacteroides, Prevotella_2, Fusobacterium, and Prevotella_9 were enriched in the C-ASD group, and Anaerostipes, Lactobacillus, Ruminococcus_gnavus_group, Lachnospiraceae_NK4A136_group, Ralstonia, Eubacterium_eligens_group, and Ruminococcus_1 were enriched in the TD group. The propionate levels, which were higher in the C-ASD group, were negatively correlated with the abundance of Lactobacillus taxa, but were positively correlated with the severity of ASD symptoms. The random forest model, based on the 16 representative discriminant genera, achieved a high accuracy (AUC = 0.924). In conclusion, we found that C-ASD is related to altered gut microbiota and SCFAs, especially decreased abundance of Lactobacillus and excessive propionate in faeces, which provide new clues to understand C-ASD and biomarkers for the diagnosis and potential strategies for treatment of the disorder. This study was registered in the Chinese Clinical Trial Registry ( www.chictr.org.cn ; trial registration number ChiCTR2100052106; date of registration: October 17, 2021).
Topics: Child; Humans; Autism Spectrum Disorder; Constipation; East Asian People; Fatty Acids, Volatile; Gastrointestinal Microbiome; Lactobacillales; Propionates; RNA, Ribosomal, 16S; Veillonellaceae
PubMed: 37925571
DOI: 10.1038/s41598-023-46566-2 -
Journal of Autoimmunity Dec 2023To investigate the compositional and functional characteristics of the gut microbiota in primary Sjögren's syndrome (pSS) and compare them with those in systemic lupus...
OBJECTIVES
To investigate the compositional and functional characteristics of the gut microbiota in primary Sjögren's syndrome (pSS) and compare them with those in systemic lupus erythematosus (SLE).
METHODS
Stool samples from 78 treatment-naïve pSS patients and 78 matched healthy controls were detected by shotgun metagenomic sequencing and compared with those from 49 treatment-naïve SLE patients. The virulence loads and mimotopes of the gut microbiota were also assessed by sequence alignment.
RESULTS
The gut microbiota of treatment-naïve pSS patients had lower richness and evenness and showed a different community distribution than that of healthy controls. The microbial species enriched in the pSS-associated gut microbiota included Lactobacillus salivarius, Bacteroides fragilis, Ruminococcus gnavus, Clostridium bartlettii, Clostridium bolteae, Veillonella parvula, and Streptococcus parasanguinis. Lactobacillus salivarius was the most discriminating species in the pSS patients, especially in those with interstitial lung disease (ILD). Among the differentiating microbial pathways, the superpathway of l-phenylalanine biosynthesis was also further enriched in pSS complicated with ILD. There were more virulence genes carried by the gut microbiota in pSS patients, most of which encoded peritrichous flagella, fimbriae, or curli fimbriae, three types of bacterial surface organelles involved in bacterial colonization and invasion. Five microbial peptides with the potential to mimic pSS-related autoepitopes were also enriched in the pSS gut. SLE and pSS shared significant gut microbial traits, including community distribution, altered microbial taxonomy and pathways, and enriched virulence genes. However, Ruminococcus torques was depleted in pSS patients but enriched in SLE patients compared to healthy controls.
CONCLUSIONS
The gut microbiota in treatment-naïve pSS patients was disturbed and shared significant similarity with that in SLE patients.
Topics: Humans; Gastrointestinal Microbiome; Sjogren's Syndrome; Lupus Erythematosus, Systemic; Metagenome; Lung Diseases, Interstitial
PubMed: 37120327
DOI: 10.1016/j.jaut.2023.103050 -
Scientific Reports Jul 2023Primary liver cancer (PLC), which includes intrahepatic cholangiocarcinoma (iCCA) and hepatocellular carcinoma (HCC), has the highest incidence of all cancer types in...
Primary liver cancer (PLC), which includes intrahepatic cholangiocarcinoma (iCCA) and hepatocellular carcinoma (HCC), has the highest incidence of all cancer types in Thailand. Known etiological factors, such as viral hepatitis and chronic liver disease do not fully account for the country's unusually high incidence. However, the gut-liver axis, which contributes to carcinogenesis and disease progression, is influenced by the gut microbiome. To investigate this relationship, fecal matter from 44 Thai PLC patients and 76 healthy controls were subjected to whole-genome metagenomic shotgun sequencing and then analyzed by marker gene-based and assembly based methods. Results revealed greater gut microbiome heterogeneity in iCCA compared to HCC and healthy controls. Two Veillonella species were found to be more abundant in iCCA samples and could distinguish iCCA from HCC and healthy controls. Conversely, Ruminococcus gnavus was depleted in iCCA patients and could distinguish HCC from iCCA samples. High Veillonella genus counts in the iCCA group were associated with enriched amino acid biosynthesis and glycolysis pathways, while enriched phospholipid and thiamine metabolism pathways characterized the HCC group with high Blautia genus counts. These findings reveal distinct landscapes of gut dysbiosis among Thai iCCA and HCC patients and warrant further investigation as potential biomarkers.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Dysbiosis; Southeast Asian People; Thailand; Bile Duct Neoplasms; Cholangiocarcinoma; Bile Ducts, Intrahepatic
PubMed: 37452065
DOI: 10.1038/s41598-023-38307-2 -
Gut Microbes Dec 2023Anti-TNF therapy can induce and maintain a remission status during intestinal bowel disease. However, up to 30% of patients do not respond to this therapy by mechanisms...
Anti-TNF therapy can induce and maintain a remission status during intestinal bowel disease. However, up to 30% of patients do not respond to this therapy by mechanisms that are unknown. Here, we show that the absence of MCJ, a natural inhibitor of the respiratory chain Complex I, induces gut microbiota changes that are critical determinants of the lack of response in a murine model of DSS-induced inflammation. First, we found that MCJ expression is restricted to macrophages in human colonic tissue. Therefore, we demonstrate by transcriptomic analysis of colon macrophages from DSS-induced mice that MCJ-deficiency is linked to the expression of genes belonging to the FcγR signaling pathway and contains an anti-TNF refractory gene signature identified in ulcerative colitis patients. The gut microbial composition changes observed upon DSS treatment in the MCJ-deficient mice revealed the increased presence of specific colitogenic members, including and , which could be associated with the non-response to TNF inhibitors. Further, we show that the presence of a microbiota associated resistance to treatment is dominant and transmissible to responsive individuals. Collectively, our findings underscore the critical role played by macrophage mitochondrial function in the gut ecological niche that can substantially affect not only the severity of inflammation but also the ability to successfully respond to current therapies.
Topics: Humans; Animals; Mice; Colitis, Ulcerative; Tumor Necrosis Factor Inhibitors; Colitis; Gastrointestinal Microbiome; Colon; Microbiota; Inflammation; Dextran Sulfate; Disease Models, Animal; Mice, Inbred C57BL
PubMed: 37842919
DOI: 10.1080/19490976.2023.2266626 -
Frontiers in Microbiology 2018Dietary and host glycans shape the composition of the human gut microbiota with keystone carbohydrate-degrading species playing a critical role in maintaining the...
Dietary and host glycans shape the composition of the human gut microbiota with keystone carbohydrate-degrading species playing a critical role in maintaining the structure and function of gut microbial communities. Here, we focused on two major human gut symbionts, the mucin-degrader ATCC 29149, and L2-63, a keystone species for the degradation of resistant starch (RS) in human colon. Using anaerobic individual and co-cultures of and grown on mucin or starch as sole carbon source, we showed that starch degradation by supported the growth of whereas did not benefit from mucin degradation by . Further we analyzed the growth (quantitative PCR), metabolite production (H NMR analysis), and bacterial transcriptional response (RNA-Seq) of cultured with RS or soluble starch (SS) in the presence or absence of . In co-culture fermentations on starch, H NMR analysis showed that benefits from transient glucose and malto-oligosaccharides released by upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products. Differential expression analysis (DESeq 2) on starch (SS and RS) showed that the presence of induced changes in transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase, in line with the ability of to utilize starch degradation products. In the RS co-culture, showed a significant increase in the induction of tryptophan (Trp) biosynthesis genes and a decrease of vitamin B12 (VitB12)-dependent methionine biosynthesis as compared to the mono-culture, suggesting that Trp and VitB12 availability become limited in the presence of . Together this study showed a direct competition between and on RS, suggesting that , the population inhabiting the mucus niche may be modulated by the supply of non-digestible carbohydrates reaching the colon such as RS.
PubMed: 30455672
DOI: 10.3389/fmicb.2018.02558 -
Frontiers in Microbiology 2023Gut microbiota plays an important role in colorectal cancer (CRC) pathogenesis through microbes and their metabolites, while oral pathogens are the major components of...
OBJECTIVE
Gut microbiota plays an important role in colorectal cancer (CRC) pathogenesis through microbes and their metabolites, while oral pathogens are the major components of CRC-associated microbes. Multiple studies have identified gut and fecal microbiome-derived biomarkers for precursors lesions of CRC detection. However, few studies have used salivary samples to predict colorectal polyps. Therefore, in order to find new noninvasive colorectal polyp biomarkers, we searched into the differences in fecal and salivary microbiota between patients with colorectal polyps and healthy controls.
METHODS
In this case-control study, we collected salivary and fecal samples from 33 patients with colorectal polyps (CP) and 22 healthy controls (HC) between May 2021 and November 2022. All samples were sequenced using full-length 16S rRNA sequencing and compared with the Nucleotide Sequence Database. The salivary and fecal microbiota signature of colorectal polyps was established by alpha and beta diversity, Linear discriminant analysis Effect Size (LEfSe) and random forest model analysis. In addition, the possibility of microbiota in identifying colorectal polyps was assessed by Receiver Operating Characteristic Curve (ROC).
RESULTS
In comparison to the HC group, the CP group's microbial diversity increased in saliva and decreased in feces ( < 0.05), but there was no significantly difference in microbiota richness ( > 0.05). The principal coordinate analysis revealed significant differences in β-diversity of salivary and fecal microbiota between the CP and HC groups. Moreover, LEfSe analysis at the species level identified and as the major contributors to the salivary microbiota, and and to the fecal microbiota of patients with polyps. Salivary and fecal bacterial biomarkers showed Area Under ROC Curve of 0.8167 and 0.8051, respectively, which determined the potential of diagnostic markers in distinguishing patients with colorectal polyps from controls, and it increased to 0.8217 when salivary and fecal biomarkers were combined.
CONCLUSION
The composition and diversity of the salivary and fecal microbiota were significantly different in colorectal polyp patients compared to healthy controls, with an increased abundance of harmful bacteria and a decreased abundance of beneficial bacteria. A promising non-invasive tool for the detection of colorectal polyps can be provided by potential biomarkers based on the microbiota of the saliva and feces.
PubMed: 37655344
DOI: 10.3389/fmicb.2023.1182346 -
Anaerobe Aug 2023We present a case of bacteremia caused by Ruminococcus gnavus in an immunocompromised patient. R. gnavus is a Gram-positive strict anaerobe bacterium that forms chains.... (Review)
Review
We present a case of bacteremia caused by Ruminococcus gnavus in an immunocompromised patient. R. gnavus is a Gram-positive strict anaerobe bacterium that forms chains. The bacteremia has been associated with an acute flare of ulcerative colitis. Anaerobic bacteremia is becoming increasingly frequent in patients with compromised gastrointestinal barrier. The role of the human microbiota and its alterations in the pathogenesis of immune-related diseases is an expanding area of interest. R. gnavus has been identified as a microorganism that may be responsible for the development of these diseases. The contribution of anaerobic bacteria to the pathogenesis of inflammatory bowel disease (IBD) is discussed, and cases reported up until 2023 were reviewed.
Topics: Humans; Bacteremia; Colitis, Ulcerative; Immunocompromised Host; Ruminococcus
PubMed: 37481231
DOI: 10.1016/j.anaerobe.2023.102762 -
Access Microbiology 2023, a Gram-positive anaerobic coccus, is a common constituent of the human gut microbiota but rarely causes any disease in humans. Herein, we report a case of...
, a Gram-positive anaerobic coccus, is a common constituent of the human gut microbiota but rarely causes any disease in humans. Herein, we report a case of bacteraemia in an immunocompromised 73-year-old man with sigmoid colon perforation. is usually reported as Gram-positive diplococci or short chains on Gram staining; however, in our patient, a blood isolate showed Gram-positive cocci in long chains, and organisms from an anaerobic subculture showed morphological diversity. This case provides insight into the morphological diversity of , which might help with the recognition of these bacteria in the preliminary identification stage on Gram staining.
PubMed: 37424554
DOI: 10.1099/acmi.0.000442 -
Frontiers in Cellular and Infection... 2023The gut micro-biome plays a pivotal role in the progression of lung cancer. However, the specific mechanisms by which the intestinal microbiota and its metabolites are...
OBJECTIVE
The gut micro-biome plays a pivotal role in the progression of lung cancer. However, the specific mechanisms by which the intestinal microbiota and its metabolites are involved in the lung cancer process remain unclear.
METHOD
Stool samples from 52 patients with lung cancer and 29 healthy control individuals were collected and subjected to 16S rRNA gene amplification sequencing and non-targeted gas/liquid chromatography-mass spectrometry metabolomics analysis. Then microbiota, metabolites and potential signaling pathways that may play an important role in the disease were filtered.
RESULTS
Firmicutes, Clostridia, Bacteroidacea, Bacteroides, and Lachnospira showed a greater abundance in healthy controls. In contrast, the was significantly upregulated in lung cancer patients. In this respect, the micro-biome of the squamous cell carcinoma(SCC)group demonstrated a relatively higher abundance of Proteobacteria, Gammaproteobacteria, Bacteroides,and Enterobacteriaceae, as well as higher abundances of Fusicatenibacter and Roseburia in adenocarcinoma(ADC) group. Metabolomic analysis showed significant alterations in fecal metabolites including including quinic acid, 3-hydroxybenzoic acid,1-methylhydantoin,3,4-dihydroxydrocinnamic acid and 3,4-dihydroxybenzeneacetic acid were significantly altered in lung cancer patients. Additionally, the and Fusicatenibacter of lung cancer were associated with multiple metabolite levels.
CONCLUSION
Our study provides essential guidance for a fundamental systematic and multilevel assessment of the contribution of gut micro-biome and their metabolites in lung cancer,which has great potential for understanding the pathogenesis of lung cancer and for better early prevention and targeted interventions.
Topics: Humans; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Feces; Metabolomics; Firmicutes; Lung Neoplasms
PubMed: 37577375
DOI: 10.3389/fcimb.2023.1170326 -
Cell & Bioscience Jan 2023Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare acquired immune-mediated neuropathy. Although microbial infection is potentially a...
OBJECTIVE
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare acquired immune-mediated neuropathy. Although microbial infection is potentially a contributing factor, a causative link between CIDP and microbial infection remains unclear. There is also no definitive biomarker for CIDP diagnostics and therapies. The present study aimed to characterize the serum metabolic profile and gut microbiome structure in CIDP.
METHODS
Targeted metabolomics profiling of serum, using liquid chromatography-mass spectrometry, and metagenomics sequencing of stool samples from a cohort of CIDP and non-CIDP subjects were performed to evaluate serum metabolic profiles and gut microbiome structure in CIDP subjects relative to healthy controls.
RESULTS
Metabolome data revealed that the bile acids profile was perturbed in CIDP with bile acids and arachidonic acid enriched significantly in CIDP versus non-CIDP controls. Metagenome data revealed that opportunistic pathogens, such as Klebsiella pneumonia and Megamonas funiformis, and genes involved in bacterial infection were notably more abundant in CIDP subjects, while gut microbes related to biotransformation of secondary bile acids were abnormal in CIDP versus non-CIDP subjects. Correlation analysis revealed that changes in secondary bile acids were associated with altered gut microbes, including Bacteroides ovatus, Bacteroides caccae, and Ruminococcus gnavus.
CONCLUSION
Bile acids and arachidonic acid metabolism were disturbed in CIDP subjects and might be affected by the dysbiosis of gut microbial flora. These findings suggest that the combination of bile acids and arachidonic acid could be used as a CIDP biomarker and that modulation of gut microbiota might impact the clinical course of CIDP.
PubMed: 36627678
DOI: 10.1186/s13578-023-00956-1