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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 -
International Journal of Food Sciences... Sep 2023Low-no-calorie sweeteners (LNCS) are used as sugar substitutes as part of strategies to reduce the risk of chronic diseases related to high sugar intake (e.g. type 2...
Low-no-calorie sweeteners (LNCS) are used as sugar substitutes as part of strategies to reduce the risk of chronic diseases related to high sugar intake (e.g. type 2 diabetes (T2D)). This study investigated how a range of sweeteners [tagatose (TA)/maltitol (MA)/sorbitol (SO)/stevia (ST)/sucralose (SU)/acesulfame K (ACK)] impact the gut microbiota of T2D subjects and healthy human adults using the SIFR® technology ( = 12). The cohort covered clinically relevant interpersonal and T2D-related differences. ACK/SU remained intact while not impacting microbial composition and metabolite production. In contrast, TA/SO and ST/MA were respectively readily and gradually fermented. ST and particularly TA/SO/MA increased bacterial density and SCFA production product-specifically: SO increased acetate (∼), whilst MA/ST increased propionate (∼). TA exerted low specificity as it increased butyrate for healthy subjects, yet propionate for T2D subjects. Overall, LNCS exerted highly compound-specific effects stressing that results obtained for one LNCS cannot be generalised to other LNCS.
Topics: Adult; Humans; Sweetening Agents; Gastrointestinal Microbiome; Propionates; Diabetes Mellitus, Type 2; Energy Intake; Sorbitol; Stevia
PubMed: 37537786
DOI: 10.1080/09637486.2023.2240037 -
Neurogastroenterology and Motility Sep 2023The etiology of irritable bowel syndrome (IBS) is unknown. Abnormal intestinal bacterial profiles and low bacterial diversity appear to play important roles in the... (Review)
Review
The etiology of irritable bowel syndrome (IBS) is unknown. Abnormal intestinal bacterial profiles and low bacterial diversity appear to play important roles in the pathophysiology of IBS. This narrative review was designed to present recent observations made relating to fecal microbiota transplantation (FMT), which implicate possible roles of 11 intestinal bacteria in the pathophysiology of IBS. The intestinal abundances of nine of these bacteria increased after FMT in patients with IBS, and these increases were inversely correlated with IBS symptoms and fatigue severity. These bacteria were Alistipes spp., Faecalibacterium prausnitzii, Eubacterium biforme, Holdemanella biformis, Prevotella spp., Bacteroides stercoris, Parabacteroides johnsonii, Bacteroides zoogleoformans, and Lactobacillus spp. The intestinal abundances of two bacteria were decreased in patients with IBS after FMT and were correlated with the severity of IBS symptoms and fatigue (Streptococcus thermophilus and Coprobacillus cateniformis). Ten of these bacteria are anaerobic and one (Streptococcus thermophilus) is facultative anaerobic. Several of these bacteria produce short-chain fatty acids, especially butyrate, which is used as an energy source by large intestine epithelial cells. Moreover, it modulates the immune response and hypersensitivity of the large intestine and decreases intestinal cell permeability and intestinal motility. These bacteria could be used as probiotics to improve these conditions. Protein-rich diets could increase the intestinal abundance of Alistipes, and plant-rich diet could increase the intestinal abundance of Prevotella spp., and consequently improve IBS and fatigue.
Topics: Humans; Irritable Bowel Syndrome; Fatigue Syndrome, Chronic; Butyrates; Epithelial Cells
PubMed: 37246923
DOI: 10.1111/nmo.14621 -
Food & Function Oct 2023Ulcerative colitis (UC) is a common inflammatory bowel disease, whose incidence is on the rise worldwide. The drugs commonly used for UC are often associated with a...
Ulcerative colitis (UC) is a common inflammatory bowel disease, whose incidence is on the rise worldwide. The drugs commonly used for UC are often associated with a number of side effects. Therefore, the development of effective, food-borne substances for UC is in line with the current needs. Egg yolk phosphatidylcholine (EYPC) is one of the abundant lipids in egg yolk and possesses various biological activities. However, its protective effect against UC has not been clarified. In this study, the anti-UC activity of EYPC was investigated using a dextran sodium sulfate (DSS)-induced colitis model of BALB/c mice. The results showed that EYPC supplementation inhibited DSS-induced colon shortening, the spleen index and disease activity index increase and intestinal structural damage. EYPC could down-regulate the levels of TNF-α, IL-1β, IL-6 and MPO in the colon and restore the number of goblet cells and the level of tight junction (TJ) proteins. Besides, EYPC modulated the composition of the gut microbiota, lowered the relative abundance of the pathogenic bacterium and upregulated the abundance of the beneficial bacteria and . These results evidenced that EYPC could attenuate DSS-induced colitis in mice and had the potential to prevent and treat UC.
Topics: Animals; Mice; Lecithins; Mice, Inbred BALB C; Egg Yolk; Colitis; Colitis, Ulcerative; Colon; Dextran Sulfate; Mice, Inbred C57BL; Disease Models, Animal
PubMed: 37781872
DOI: 10.1039/d3fo02885b -
EBioMedicine Nov 2023Microplastics (MPs) have garnered widespread attention because of their presence in human placenta, stool, and even blood. Ingestion is considered the major route of...
BACKGROUND
Microplastics (MPs) have garnered widespread attention because of their presence in human placenta, stool, and even blood. Ingestion is considered the major route of human exposure to MPs. It has been found that the consumption of food and water is associated with more MP abundance in human stools. The usage of plastic containers, particularly feeding bottles, may be a major contributor to MP contamination. However, human exposure to MPs and potential factors that influence exposure, especially for preschoolers, remains largely unknown. When exposed to MPs, mice exhibited gut microbiota dysbiosis, including alterations in diversity indices, a decreased relative abundance of probiotics and an increased abundance of pathogenic bacteria. Such results have also been observed in human gut in vitro models, however, the actual association between MP exposure and human intestinal microbiota remains unclear. Therefore, this study aimed to evaluate MP concentrations in preschoolers' stools, explore possible dietary factors that influence preschooler exposure to MPs, and investigate their potential association with the gut microbiota.
METHODS
A cross-sectional study was conducted in Xiamen, China in October 2022. We investigated the feeding behaviours and dietary habits of preschool children. A total of 69 couples of stool samples were collected and analyzed for MPs test and gut microbiota analysis. Pyrolysis-gas chromatography coupled with mass spectrometry (Py-GC/MS) was used for quantifying 11 types of MPs. The gut microbiota composition was analyzed by 16S rRNA gene sequencing.
FINDINGS
The results showed that only polyvinyl chloride (PVC), polyethylene terephthalate (PET), polyethylene (PE), and polyamide 6 (PA6) were detected in 85.5% stool samples, with concentrations of 317.4 (152.0, 491.9) μg/g dw, 299.0 (196.1, 619.9) μg/g dw, 206.2 (154.1, 240.3) μg/g dw, and 17.9 (13.4, 18.6) μg/g dw, respectively. The median estimated daily intake (EDI) for preschoolers was 425.9 (272.5, 762.3) μg/kg-bw/d. Dairy intake may influence MP concentration in preschoolers' stools, and the usage of feeding bottles may be a specific source of MP contamination. Moreover, higher PVC concentrations were observed in the stools when the children took more time to eat a meal. MP exposure was inversely associated with alpha indices and possibly affected certain probiotic taxa, such as Parabacteroides and Alistipes, in preschool children.
INTERPRETATION
Our data provided baseline evidence for MP exposure doses and potential dietary factors that may influence MP exposure in preschoolers. These findings supported the perspective that MP exposure might be associated with the disturbance of gut microbiota. Further studies focusing on sensitive populations with larger sample sizes are needed.
FUNDING
This study was funded by the National Natural Science Foundation of China (grant number: 82003412), the Shanghai Municipal Health Commission (grant number: 20214Y0019), and the Project of Shanghai Municipal Financial Professional foundation (Food Safety Risk Assessment) (grant number: RA-2022-06).
Topics: Humans; Child, Preschool; Animals; Mice; Microplastics; Plastics; Gastrointestinal Microbiome; Pilot Projects; RNA, Ribosomal, 16S; Cross-Sectional Studies; China; Polyethylene; Water Pollutants, Chemical
PubMed: 37837933
DOI: 10.1016/j.ebiom.2023.104828 -
Biology Direct Aug 2023The response rate to obeticholic acid (OCA), a potential therapeutic agent for non-alcoholic fatty liver disease, is limited. This study demonstrated that upregulation...
The response rate to obeticholic acid (OCA), a potential therapeutic agent for non-alcoholic fatty liver disease, is limited. This study demonstrated that upregulation of the alternative bile acid synthesis pathway increases the OCA treatment response rate. The hepatic transcriptome and bile acid metabolite profile analyses revealed that the alternative bile acid synthesis pathway (Cyp7b1 and muricholic acid) in the OCA-responder group were upregulated compared with those in the OCA-non-responder group. Intestinal microbiome analysis also revealed that the abundances of Bacteroidaceae, Parabacteroides, and Bacteroides, which were positively correlated with the alternative bile acid synthesis pathway, were higher in the OCA-responder group than in the non-responder group. Pre-study hepatic mRNA levels of Cyp8b1 (classic pathway) were downregulated in the OCA-responder group. The OCA response rate increased up to 80% in cases with a hepatic Cyp7b1/Cyp8b1 ratio ≥ 5.0. Therefore, the OCA therapeutic response can be evaluated based on the Cyp7b1/Cyp8b1 ratio or the alternative/classic bile acid synthesis pathway activity.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Steroid 12-alpha-Hydroxylase; Bile Acids and Salts; Biomarkers
PubMed: 37626369
DOI: 10.1186/s13062-023-00407-4 -
Nature Communications Feb 2024Fusobacterium nucleatum (F. nucleatum) promotes intestinal tumor growth and its relative abundance varies greatly among patients with CRC, suggesting the presence of...
Fusobacterium nucleatum (F. nucleatum) promotes intestinal tumor growth and its relative abundance varies greatly among patients with CRC, suggesting the presence of unknown, individual-specific effectors in F. nucleatum-dependent carcinogenesis. Here, we identify that F. nucleatum is enriched preferentially in KRAS p.G12D mutant CRC tumor tissues and contributes to colorectal tumorigenesis in Villin-Cre/Kras mice. Additionally, Parabacteroides distasonis (P. distasonis) competes with F. nucleatum in the G12D mouse model and human CRC tissues with the KRAS mutation. Orally gavaged P. distasonis in mice alleviates the F. nucleatum-dependent CRC progression. F. nucleatum invades intestinal epithelial cells and binds to DHX15, a protein of RNA helicase family expressed on CRC tumor cells, mechanistically involving ERK/STAT3 signaling. Knock out of Dhx15 in Villin-Cre/Kras mice attenuates the CRC phenotype. These findings reveal that the oncogenic effect of F. nucleatum depends on somatic genetics and gut microbial ecology and indicate that personalized modulation of the gut microbiota may provide a more targeted strategy for CRC treatment.
Topics: Animals; Humans; Mice; Carcinogenesis; Colorectal Neoplasms; Fusobacterium nucleatum; Proto-Oncogene Proteins p21(ras); RNA Helicases
PubMed: 38402201
DOI: 10.1038/s41467-024-45572-w -
Frontiers in Cellular and Infection... 2023Intermittent energy restriction (IER) is an effective weight loss strategy. However, little is known about the dynamic effects of IER on the brain-gut-microbiome axis.
OBJECTIVE
Intermittent energy restriction (IER) is an effective weight loss strategy. However, little is known about the dynamic effects of IER on the brain-gut-microbiome axis.
METHODS
In this study, a total of 25 obese individuals successfully lost weight after a 2-month IER intervention. FMRI was used to determine the activity of brain regions. Metagenomic sequencing was performed to identify differentially abundant gut microbes and pathways in from fecal samples.
RESULTS
Our results showed that IER longitudinally reduced the activity of obese-related brain regions at different timepoints, including the inferior frontal orbital gyrus in the cognitive control circuit, the putamen in the emotion and learning circuit, and the anterior cingulate cortex in the sensory circuit. IER longitudinally reduced abundance across multiple timepoints while elevating the abundance of obesity-related , and . Correlation analysis revealed longitudinally correlations between gut bacteria abundance alterations and brain activity changes.
CONCLUSIONS
There was dynamical alteration of BGM axis (the communication of with specific brain regions) during the weight loss under the IER.
Topics: Humans; Gastrointestinal Microbiome; Caloric Restriction; Escherichia coli; Obesity; Weight Loss
PubMed: 38173792
DOI: 10.3389/fcimb.2023.1269548 -
Respiratory Research Jan 2024Growing evidence from observational studies and clinical trials suggests that the gut microbiota is associated with tuberculosis (TB). However, it is unclear whether any...
BACKGROUND
Growing evidence from observational studies and clinical trials suggests that the gut microbiota is associated with tuberculosis (TB). However, it is unclear whether any causal relationship exists between them and whether causality is bidirectional.
METHODS
A bidirectional two-sample Mendelian randomization (MR) analysis was performed. The genome-wide association study (GWAS) summary statistics of gut microbiota were obtained from the MiBioGen consortium, while the GWAS summary statistics of TB and its specific phenotypes [respiratory tuberculosis (RTB) and extrapulmonary tuberculosis (EPTB)] were retrieved from the UK Biobank and the FinnGen consortium. And 195 bacterial taxa from phylum to genus were analyzed. Inverse variance weighted (IVW), MR-Egger regression, maximum likelihood (ML), weighted median, and weighted mode methods were applied to the MR analysis. The robustness of causal estimation was tested using the heterogeneity test, horizontal pleiotropy test, and leave-one-out method.
RESULTS
In the UK Biobank database, we found that 11 bacterial taxa had potential causal effects on TB. Three bacterial taxa genus.Akkermansia, family.Verrucomicrobiacea, order.Verrucomicrobiales were validated in the FinnGen database. Based on the results in the FinnGen database, the present study found significant differences in the characteristics of gut microbial distribution between RTB and EPTB. Four bacterial taxa genus.LachnospiraceaeUCG010, genus.Parabacteroides, genus.RuminococcaceaeUCG011, and order.Bacillales were common traits in relation to both RTB and TB, among which order.Bacillales showed a protective effect. Additionally, family.Bacteroidacea and genus.Bacteroides were identified as common traits in relation to both EPTB and TB, positively associating with a higher risk of EPTB. In reverse MR analysis, no causal association was identified. No significant heterogeneity of instrumental variables (IVs) or horizontal pleiotropy was found.
CONCLUSION
Our study supports a one-way causal relationship between gut microbiota and TB, with gut microbiota having a causal effect on TB. The identification of characteristic gut microbiota provides scientific insights for the potential application of the gut microbiota as a preventive, diagnostic, and therapeutic tool for TB.
Topics: Humans; Gastrointestinal Microbiome; Mendelian Randomization Analysis; Genome-Wide Association Study; Tuberculosis; Tuberculosis, Pulmonary
PubMed: 38178098
DOI: 10.1186/s12931-023-02652-7 -
Indian Journal of Gastroenterology :... Feb 2024Inflammatory bowel diseases (IBD) are chronic inflammatory gut disorders, majorly classified as ulcerative colitis and Crohn's disease. The complex, multifactorial... (Review)
Review
Inflammatory bowel diseases (IBD) are chronic inflammatory gut disorders, majorly classified as ulcerative colitis and Crohn's disease. The complex, multifactorial etiopathogenesis of IBD involves genetic predisposition, environmental cues, aberrant mucosal immune response and a disturbed gut microbiota. Epidemiological trends, studies in gnotobiotic mice models and genome-wide association studies, identifying genes involved in microbial handling, together mount evidence in support of the gut microbiota playing a pivotal role in IBD pathogenesis. Both Crohn's disease and ulcerative colitis are characterized by severe dysbiosis of the gut microbiome, marked by an expansion of detrimental taxa and concomitant depletion of beneficial members. IBD is characterized by reduction in abundances of bacterial genera involved in production of short-chain fatty acids, bio-transformations of bile acids and synthesis of indole-based tryptophan compounds such as Faecalibacterium, Ruminococcus, Coprococcus, Dorea, Parabacteroides, Eubacterium, Oscillibacter and Prevotella and elevation in members of phyla Proteobacteria and Actinobacteria. This imbalance not only results in exaggerated immune signaling towards the microbial antigens, but also results in an altered metabolomic milieu that triggers additional inflammatory cascades. The present review provides insights into the bacterial dysbiosis observed across different intestinal sites and their metabolomic imprints participating in IBD.
Topics: Animals; Mice; Colitis, Ulcerative; Crohn Disease; Dysbiosis; Genome-Wide Association Study; Inflammatory Bowel Diseases; Bacteria
PubMed: 38374283
DOI: 10.1007/s12664-024-01541-1