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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 -
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 -
PloS One 2023Attention deficit hyperactivity disorder (ADHD) is a common mental behavioral disorder in children. Alterations in gut microbiota composition are associated with...
Attention deficit hyperactivity disorder (ADHD) is a common mental behavioral disorder in children. Alterations in gut microbiota composition are associated with neurological disorders. We aimed to investigate whether a ketogenic diet (KD) can be an alternative therapy for ADHD by altering the gut microbiota. Male spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats were randomly allocated to the normal diet (ND), methylphenidate (MPH), and KD groups. SHR in groups KD and MPH exhibited a significant increase in behavioral characteristics of ADHD, such as distance moved and immobility time. KD and MPH treatment led to a significant elevation in concentrations of 5-HT, AC, cAMP, and NE of brain tissue and the expression of DRD1, DAT, PKA, DARPP32, and cAMP at the protein level in WKY rats and SHR. KD and MPH significantly increased the richness and diversity of gut microbiota in SHR. The abundance of Ruminococcus_gauvreauii_group, Bacteroides, Bifidobacterium, and Blautia significantly increased, whereas that of Lactobacillus, Romboutsia, Facklamia, and Turicibacter significantly declined in the KD group compared with the ND group. The gut microbiota in the KD group of SHR mainly participated in amino acid metabolism- and sugar metabolism-related pathways. KD might alleviate behavioral disorders in ADHD by regulating gut microbiota. This study provides novel insights for the use of KD in treating ADHD.
Topics: Rats; Male; Animals; Attention Deficit Disorder with Hyperactivity; Rats, Inbred WKY; Central Nervous System Stimulants; Gastrointestinal Microbiome; Diet, Ketogenic; Methylphenidate; Rats, Inbred SHR; Disease Models, Animal
PubMed: 37585373
DOI: 10.1371/journal.pone.0289133 -
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 -
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 -
Skin Research and Technology : Official... Sep 2023Prior observational studies have identified a relationship between the composition of gut microbiota and the onset of acne. To ascertain the causal relationship...
BACKGROUND
Prior observational studies have identified a relationship between the composition of gut microbiota and the onset of acne. To ascertain the causal relationship underlying this association, we adopted the Mendelian randomization (MR) method, which offers a powerful approach to causal inference.
METHODS
Summary statistics on gut microbiota and acne were obtained from the MiBioGen and FinnGen consortium, respectively. The causal relationship was assessed using multiple methods in a two-sample framework, including MR Egger, weighted median, inverse variance weighted (IVW), and weighted mode. Furthermore, the heterogeneity and horizontal pleiotropy analyses were conducted, along with the leave-one-out method.
RESULTS
The IVW estimation indicated that Allisonella (odds ratio [OR] = 1.42, 95% confidence interval [CI] = 1.18-1.70, p = 0.0002) and Bacteroides (OR = 2.25, 95% CI = 1.48-3.42, p = 0.0001) have adverse effects on acne. By contrast, Ruminococcus torques group (OR = 0.41, 95% CI = 0.25-0.65, p = 0.0002) showed a beneficial effect on acne. In addition, Candidatus soleaferrea (OR = 0.75, 95% CI = 0.60-0.95, p = 0.0149), Eubacterium coprostanoligenes group (OR = 0.67, 95% CI = 0.47-0.95, p = 0.0230), Fusicatenibacter (OR = 0.71, 95% CI = 0.52-0.97, p = 0.02897), and Lactobacillus (OR = 0.72, 95% CI = 0.58-0.90, p = 0.0046) showed suggestive associations with acne.
CONCLUSION
The present investigation suggests a causal effect of gut microbiota on acne.
Topics: Humans; Gastrointestinal Microbiome; Mendelian Randomization Analysis; Acne Vulgaris
PubMed: 37753688
DOI: 10.1111/srt.13473 -
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 -
Clocks & Sleep Sep 2023Increasing evidence suggests a correlation between changes in the composition of gut microbiota and sleep-related phenotypes. However, it remains uncertain whether these...
Increasing evidence suggests a correlation between changes in the composition of gut microbiota and sleep-related phenotypes. However, it remains uncertain whether these associations indicate a causal relationship. The genome-wide association study summary statistics data of gut microbiota ( = 18,340) was downloaded from the MiBioGen consortium and the data of sleep-related phenotypes were derived from the UK Biobank, the Medical Research Council-Integrative Epidemiology Unit, Jones SE, the FinnGen consortium. To test and estimate the causal effect of gut microbiota on sleep traits, a two-sample Mendelian randomization (MR) approach using multiple methods was conducted. A series of sensitive analyses, such as horizontal pleiotropy analysis, heterogeneity test, MR Steiger directionality test and "leave-one-out" analysis as well as reverse MR analysis, were conducted to assess the robustness of MR results. The genus has a negative causal effect on getting up in the morning (odd ratio = 0.977, 95% confidence interval: 0.965-0.988, = 7.28 × 10). A higher abundance of order Enterobacteriales and family Enterobacteriaceae contributed to becoming an "evening person". Six and two taxa were causally associated with longer and shorter sleep duration, respectively. Specifically, two SCFA-produced genera including (odd ratio = 1.029, 95% confidence interval = 1.012-1.046, = 6.11 × 10) and contribute to extending sleep duration. Two obesity-related genera such as (odd ratio = 1.024, 95% confidence interval: 1.011-1.036, = 1.74 × 10) and were found to be increased and decreased risk of snoring, respectively. In addition, we found two risk taxa of insomnia such as the order Selenomonadales and one of its classes called Negativicutes. All of the sensitive analysis and reverse MR analysis results indicated that our MR results were robust. Our study revealed the causal effect of gut microbiota on sleep and identified causal risk and protective taxa for chronotype, sleep duration, snoring and insomnia, which has the potential to provide new perspectives for future mechanistic and clinical investigations of microbiota-mediated sleep abnormal patterns and provide clues for developing potential microbiota-based intervention strategies for sleep-related conditions.
PubMed: 37754355
DOI: 10.3390/clockssleep5030037 -
Metabolites Dec 2023Advances in high-throughput DNA sequencing have propelled research into the human microbiome and its link to metabolic health. We explore microbiome analysis methods,... (Review)
Review
Advances in high-throughput DNA sequencing have propelled research into the human microbiome and its link to metabolic health. We explore microbiome analysis methods, specifically emphasizing metabolomics, how dietary choices impact the production of microbial metabolites, providing an overview of studies examining the connection between enterotypes and diet, and thus, improvement of personalized dietary recommendations. Acetate, propionate, and butyrate constitute more than 95% of the collective pool of short-chain fatty acids. Conflicting data on acetate's effects may result from its dynamic signaling, which can vary depending on physiological conditions and metabolic phenotypes. Human studies suggest that propionate has overall anti-obesity effects due to its well-documented chemistry, cellular signaling mechanisms, and various clinical benefits. Butyrate, similar to propionate, has the ability to reduce obesity by stimulating the release of appetite-suppressing hormones and promoting the synthesis of leptin. Tryptophan affects systemic hormone secretion, with indole stimulating the release of GLP-1, which impacts insulin secretion, appetite suppression, and gastric emptying. Bile acids, synthesized from cholesterol in the liver and subsequently modified by gut bacteria, play an essential role in the digestion and absorption of dietary fats and fat-soluble vitamins, but they also interact directly with intestinal microbiota and their metabolites. One study using statistical methods identified primarily two groupings of enterotypes and . The -dominated enterotype, P-type, in humans correlates with vegetarians, high-fiber and carbohydrate-rich diets, and traditional diets. Conversely, individuals who consume diets rich in animal fats and proteins, typical in Western-style diets, often exhibit the Bacteroides-dominated, B-type, enterotype. The P-type showcases efficient hydrolytic enzymes for plant fiber degradation but has limited lipid and protein fermentation capacity. Conversely, the B-type features specialized enzymes tailored for the degradation of animal-derived carbohydrates and proteins, showcasing an enhanced saccharolytic and proteolytic potential. Generally, models excel at predictions but often struggle to fully elucidate why certain substances yield varied responses. These studies provide valuable insights into the potential for personalized dietary recommendations based on enterotypes.
PubMed: 38132864
DOI: 10.3390/metabo13121182 -
Journal of Gastrointestinal and Liver... Sep 2023Traditional cardiovascular risk factors are established predictors of heart failure (HF). However, the human gut microbiota is suggested to potentially interact with the...
BACKGROUND AND AIMS
Traditional cardiovascular risk factors are established predictors of heart failure (HF). However, the human gut microbiota is suggested to potentially interact with the cardiovascular system through the "gut-heart axis", which induces inflammation and contributes to HF pathogenesis. This systematic review aims to confirm the interconnection between the gut microbiome in HF patients.
METHODS
Peer-reviewed human studies comparing the gut microbiota profile in adult patients with HF and healthy controls (HCs) up to April 18, 2022, were searched in Ovid MEDLINE, Ovid EMBASE, SCOPUS, and the Cochrane Library. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS).
RESULTS
A total of nine studies, including 317 HF patients and 510 HCs, were included in the review. Decreased gut microbiota richness and similar microbial diversity (alpha diversity), and significantly different gut microbiota composition (beta diversity) were observed between HF patients and HCs. In comparison to HCs, HF patients had a greater abundance of Actinobacteria, Proteobacteria, and Synergistetes phyla; Enterococcus, Escherichia, Klebsiella, Lactobacillus, Streptococcus, and Veilonella genera and Ruminococcus gnavus, Streptococcus sp., and Veilonella sp. species. In contrast, there was decreased abundance of Firmicutes phylum; Blautia, Eubacterium, Faecalibacterium, and Lachnospiraceae FCS020 genera; and Dorea longicatena, Eubacterium rectale, Faecalibacterium prausnitzii, Oscillibacter sp., and Sutterella wadsworthensis species in HF patients.
CONCLUSIONS
Gut microbiota diversity, richness, and composition in HF patients differ significantly from the healthy population. Overall, short-chain fatty acid (SCFA)-producing gut microbiota was depleted in HF patients. However, different underlying comorbidities, environments, lifestyles, and dietary choices could affect gut microbiota heterogeneity.
Topics: Adult; Humans; Gastrointestinal Microbiome; Diet; Bacteria; Heart Failure; Inflammation
PubMed: 37774217
DOI: 10.15403/jgld-4779