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Scientific Reports Nov 2023The aim of this study was to investigate the influence of Bacteroides vulgatus (BV), Clostridium perfringens (CP), Parabacteroides distasonis (PD) and Ruminococcus albus...
The aim of this study was to investigate the influence of Bacteroides vulgatus (BV), Clostridium perfringens (CP), Parabacteroides distasonis (PD) and Ruminococcus albus (RA) lysates on secretion of selected cytokines by PBMC, MDM and HT-29 cells, as well as to determine the potential mechanisms of their action in the development of asthma. Enzyme-linked immunosorbent assays were used to analyze the effect of BV, CP, PD and RA lysates on the secretion of IL-1β, IL-6, IL-10 and TNF-α by human PBMC, MDM and HT-29 cells. BV and CP lysates significantly lowered IL-1β secretion by MDM vs. control (p < 0.05 and p < 0.001 respectively) but only at a dose of 400 µg lysate. The secretions of IL-6 by PBMC and MDM were elevated significantly above control values (p < 0.05) after administration of CP and PD lysates. BV, CP and PD lysates (100 µg) significantly increased IL-10 secretion by PBMC vs. control (p < 0.05). CP, PD and RA lysates (400 µg) significantly increased IL-10 secretion by MDM vs. control (p < 0.001). BV lysate (400 µg) also significantly increased IL-10 secretion by MDM as compared to control (p < 0.05). In PBMC and MDM, the production levels of the anti-inflammatory cytokine were increased by all the bacterial lysates used in a dose-dependent manner.
Topics: Humans; Interleukin-10; Interleukin-6; Gastrointestinal Microbiome; Leukocytes, Mononuclear; Cytokines; Asthma
PubMed: 37957277
DOI: 10.1038/s41598-023-47003-0 -
Annals of Surgery Oct 2023External exposures, the host, and the microbiome interact in oncology. We aimed to investigate tumoral microbiomes in young-onset rectal cancers (YORCs) for profiles...
OBJECTIVE
External exposures, the host, and the microbiome interact in oncology. We aimed to investigate tumoral microbiomes in young-onset rectal cancers (YORCs) for profiles potentially correlative with disease etiology and biology.
BACKGROUND
YORC is rapidly increasing, with 1 in 4 new rectal cancer cases occurring under the age of 50 years. Its etiology is unknown.
METHODS
YORC (<50 y old) or later-onset rectal cancer (LORC, ≥50 y old) patients underwent pretreatment biopsied of tumor and tumor-adjacent normal (TAN) tissue. After whole genome sequencing, metagenomic analysis quantified microbial communities comparing tumors versus TANs and YORCs versus LORCs, controlling for multiple testing. Response to neoadjuvant therapy (NT) was categorized as major pathological response (MPR, ≤10% residual viable tumor) versus non-MPR.
RESULTS
Our 107 tumors, 75 TANs from 37 (35%) YORCs, and 70 (65%) LORCs recapitulated bacterial species were previously associated with colorectal cancers (all P <0.0001). YORC and LORC tumoral microbiome signatures were distinct. After NT, 13 patients (12.4%) achieved complete pathologic response, whereas MPR occurred in 47 patients (44%). Among YORCs, MPR was associated with Fusobacterium nucleaum , Bacteroides dorei, and Ruminococcus bromii (all P <0.001), but MPR in LORC was associated with R. bromii ( P <0.001). Network analysis of non-MPR tumors demonstrated a preponderance of oral bacteria not observed in MPR tumors.
CONCLUSIONS
Microbial signatures were distinct between YORC and LORC. Failure to achieve an MPR was associated with oral bacteria in tumors. These findings urge further studies to decipher correlative versus mechanistic associations but suggest a potential for microbial modulation to augment current treatments.
Topics: Humans; Middle Aged; Neoadjuvant Therapy; Rectal Neoplasms; Biopsy; Microbiota
PubMed: 37465976
DOI: 10.1097/SLA.0000000000006015 -
Microorganisms Aug 2023Globally, colorectal cancer (CRC) is the second most common cause of mortality worldwide. Considerable evidence indicates that dysbiosis of the gut microbial community... (Review)
Review
Globally, colorectal cancer (CRC) is the second most common cause of mortality worldwide. Considerable evidence indicates that dysbiosis of the gut microbial community and its metabolite secretions play a fundamental role in advanced adenoma (ADA) and CRC development and progression. This study is a systematic review that aims to assess the clinical association between gut microbial markers and/or gut and circulating metabolites with ADA and CRC. Five electronic databases were searched by four independent reviewers. Only controlled trials that compared ADA and/or CRC with healthy control (HC) using either untargeted (16s rRNA gene or whole genome sequencing) or targeted (gene-based real-time PCR) identification methods for gut microbiome profile, or untargeted or targeted metabolite profiling approaches from the gut or serum/plasma, were eligible. Three independent reviewers evaluated the quality of the studies using the . Twenty-four studies were eligible. We identified strong evidence of two microbial markers and for ADA vs. CRC, and nine microbial markers -Lachnoclostridium, -Ruminococcus, spp., , Enterobacteriaceae, spp., Bacteroides, -, spp.-, , and for CRC vs. HC. The remaining metabolite marker evidence between the various groups, including ADA vs. HC, ADA vs. HC, and CRC vs. HC, was not of sufficient quality to support additional findings. The identified gut microbial markers can be used in a panel for diagnosing ADA and/or CRC. Further research in the metabolite markers area is needed to evaluate the possibility to use in diagnostic or prognostic markers for colorectal cancer.
PubMed: 37630597
DOI: 10.3390/microorganisms11082037 -
Cancer Medicine Jul 2023Gut microbiota plays a significant role in the colorectal cancer (CRC) process. Ectopic colonization of multiple oral bacteria is reportedly associated with CRC...
BACKGROUND
Gut microbiota plays a significant role in the colorectal cancer (CRC) process. Ectopic colonization of multiple oral bacteria is reportedly associated with CRC pathogenesis and progression, but the details remain unclear.
METHODS
We enrolled a cohort of 50 CRC patients and 52 healthy controls from an East China population. Taxonomic and functional analysis of the fecal microbiota were performed using 16S rDNA (50 + 52 samples) and shotgun metagenomic sequencing (8 + 6 samples), respectively, with particular attention paid to gut-colonized oral bacteria.
RESULTS AND CONCLUSIONS
The results showed more detected bacterial species but lower species evenness within the samples from CRC patients. To determine the specific bacteria enriched in each group, we analyzed their possible protective, carcinogenic, or opportunistic roles in the CRC process. Among the ectopic oral bacteria, we observed a significant increase in the abundance of Fusobacterium and decreased abundance of Prevotella and Ruminococcus in the CRC group. Main differences in the functional composition of these two groups were related to energy metabolism and biosynthesis, especially the glycolytic pathway. Furthermore, we validated the colonization of Fusobacterium nucleatum subsp. animalis within CRC tissues and studied its impact on the host intestinal epithelium and tumor cells. With high selectivity for cancerous tissues, this subspecies promoted CRC cell proliferation and induced potential DNA damage.
Topics: Humans; Gastrointestinal Microbiome; Colorectal Neoplasms; Bacteria; Microbiota; Carcinogenesis
PubMed: 37260140
DOI: 10.1002/cam4.6194 -
Frontiers in Microbiology 2024This study aimed to clarify the relationship between the gut microbiota and osteoporosis combining Mendelian randomization (MR) analysis with animal experiments.
BACKGROUND
This study aimed to clarify the relationship between the gut microbiota and osteoporosis combining Mendelian randomization (MR) analysis with animal experiments.
METHODS
We conducted an analysis on the relationship between differential bacteria and osteoporosis using open-access genome-wide association study (GWAS) data on gut microbe and osteoporosis obtained from public databases. The analysis was performed using two-sample MR analysis, and the causal relationship was examined through inverse variance weighting (IVW), MR Egger, weighted median, and weighted mode methods. Bilateral oophorectomy was employed to replicate the mouse osteoporosis model, which was assessed by micro computed tomography (CT), pathological tests, and bone transformation indexes. Additionally, 16S rDNA sequencing was conducted on fecal samples, while SIgA and indexes of IL-6, IL-1β, and TNF-α inflammatory factors were examined in colon samples. Through immunofluorescence and histopathology, expression levels of tight junction proteins, such as claudin-1, ZO-1, and occludin, were assessed, and conduct correlation analysis on differential bacteria and related environmental factors were performed.
RESULTS
A positive correlation was observed between and the risk of osteoporosis, while showed a negative correlation with the risk of osteoporosis. Furthermore, there was no evidence of heterogeneity or pleiotropy. The successful replication of the mouse osteoporosis model was assessed, and it was found that the abundance of the was significantly reduced, while the abundance of was significantly increased in the ovariectomized (OVX)-mice. The intestinal SIgA level of OVX mice decreased, the expression level of inflammatory factors increased, barrier damage occurred, and the content of LPS in the colon and serum significantly increased. The abundance level of is strongly positively correlated with bone formation factors, gut barrier indicators, bone density, bone volume fraction, and trabecular bone quantity, whereas it was strongly negatively correlated with bone resorption factors and intestinal inflammatory factors, The abundance level of shows a strong negative correlation with bone formation factors, gut barrier indicators, and bone volume fraction, and a strong positive correlation with bone resorption factors and intestinal inflammatory factors.
CONCLUSION
and may regulate the development of osteoporosis through the microbiota-gut-bone axis.
PubMed: 38835486
DOI: 10.3389/fmicb.2024.1373013 -
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 -
Applied Microbiology and Biotechnology Jul 2023As common mental disorders, depression and anxiety impact people all around the world. Recent studies have found that the gut microbiome plays an important role in...
As common mental disorders, depression and anxiety impact people all around the world. Recent studies have found that the gut microbiome plays an important role in mental health. It is becoming possible to treat mental disorders by regulating the composition of the gut microbiota. Bacillus licheniformis is a probiotic used to treat gut diseases through balancing the gut microbiome during lasting years. Considering the role of gut microbiota in the gut-brain axis, this study used chronic unpredictable mild stress (CUMS) model rats to explore whether Bacillus licheniformis can prevent and treat depression and anxiety. We found that B. licheniformis reduced the depressive-like and anxiety-like behaviours of the rats during the CUMS process. Meanwhile, B. licheniformis changed the gut microbiota composition; increased the short chain fatty acids (SCFAs) in the colon, decreased kynurenine, norepinephrine, and glutamate levels; and increased the tryptophan, dopamine, epinephrine, and γ-aminobutyric acid (GABA) in the brain. After correlation analysis, we found Parabacteroides, Anaerostipes, Ruminococcus-2, and Blautia showed significant correlation with neurotransmitters and SCFAs, indicating the gut microbiome plays an important role in B. licheniformis reducing depressive-like behaviours. Therefore, this study suggested B. licheniformis may prevent depressive-like and anxiety-like behaviours while regulating the gut microbiota composition and increasing the SCFA levels in the colon to alter the levels of the neurotransmitters in the brain. KEY POINTS: • B. licheniformis reduced depressive-like and anxiety-like behaviours induced by the chronic unpredictable mild stress. • GABA levels in the brain are assonated with B. licheniformis regulating depressive-like and anxiety-like behaviours. • Gut microbiota composition alteration followed by metabolic changes may play a role in the GABA levels increase.
Topics: Rats; Animals; Depression; Bacillus licheniformis; Behavior, Animal; Anxiety; Neurotransmitter Agents
PubMed: 37209162
DOI: 10.1007/s00253-023-12580-7 -
Internal and Emergency Medicine Aug 2023This is a literature review describes Crohn's disease (CD) concomitant with breast cancer and summarizes possible common pathogenic mechanisms shared by the two diseases... (Review)
Review
This is a literature review describes Crohn's disease (CD) concomitant with breast cancer and summarizes possible common pathogenic mechanisms shared by the two diseases involving the IL-17 and NF-κB signaling pathways. Inflammatory cytokines including TNF-α and Th17 cells in CD patients can induce activation of the ERK1/2, NF-κB and Bcl-2 pathways. Hub genes are involved in the generation of cancer stem cells (CSCs) and are related to inflammatory mediators, including CXCL8, IL1-β and PTGS2, which promote inflammation and breast cancer growth, metastasis, and development. CD activity is highly associated with altered intestinal microbiota processes, including secretion of complex glucose polysaccharides by Ruminococcus gnavus colonies; furthermore, γ-proteobacteria and Clostridium are associated with CD recurrence and active CD, while Ruminococcaceae, Faecococcus and Vibrio desulfuris are associated with CD remission. Intestinal microbiota disorder promotes breast cancer occurrence and development. Bacteroides fragilis can produce toxins that induce breast epithelial hyperplasia and breast cancer growth and metastasis. Gut microbiota regulation can also improve chemotherapy and immunotherapy efficacy in breast cancer treatment. Intestinal inflammation can affects the brain through the brain-gut axis, which activates the hypothalamic‒pituitary‒adrenal (HPA) axis to induce anxiety and depression in patients; these effects can inhibit the antitumor immune responses of the immune system and promote breast cancer occurrence in patients with CD. There are few studies on the treatment of patients with CD concomitant with breast cancer, but published studies show three main strategies: new biological agents combined with breast cancer treatment methods, intestinal fecal bacteria transplantation, and dietary treatment.
Topics: Humans; Female; Crohn Disease; NF-kappa B; Breast Neoplasms; Intestinal Mucosa; Neoplasm Recurrence, Local; Inflammation
PubMed: 37138170
DOI: 10.1007/s11739-023-03281-0 -
Cancer Medicine Sep 2023Aging is one of the factors leading to cancer. Gut microbiota is related to aging and colorectal cancer (CRC).
BACKGROUND
Aging is one of the factors leading to cancer. Gut microbiota is related to aging and colorectal cancer (CRC).
METHODS
A total of 11 metagenomic data sets related to CRC were collected from the R package curated Metagenomic Data. After batch effect correction, healthy individuals and CRC samples were divided into three age groups. Ggplot2 and Microbiota Process packages were used for visual description of species composition and PCA in healthy individuals and CRC samples. LEfSe analysis was performed for species relative abundance data in healthy/CRC groups according to age. Spearman correlation coefficient of age-differentiated bacteria in healthy individuals and CRC samples was calculated separately. Finally, the age prediction model and CRC risk prediction model were constructed based on the age-differentiated bacteria.
RESULTS
The structure and composition of the gut microbiota were significantly different among the three groups. For example, the abundance of Bacteroides vulgatus in the old group was lower than that in the other two groups, the abundance of Bacteroides fragilis increased with aging. In addition, seven species of bacteria whose abundance increases with aging were screened out. Furthermore, the abundance of pathogenic bacteria (Escherichia_coli, Butyricimonas_virosa, Ruminococcus_bicirculans, Bacteroides_fragilis and Streptococcus_vestibularis) increased with aging in CRCs. The abundance of probiotics (Eubacterium_eligens) decreased with aging in CRCs. The age prediction model for healthy individuals based on the 80 age-related differential bacteria and model of CRC patients based on the 58 age-related differential bacteria performed well, with AUC of 0.79 and 0.71, respectively. The AUC of CRC risk prediction model based on 45 disease differential bacteria was 0.83. After removing the intersection between the disease-differentiated bacteria and the age-differentiated bacteria from the healthy samples, the AUC of CRC risk prediction model based on remaining 31 bacteria was 0.8. CRC risk prediction models for each of the three age groups showed no significant difference in accuracy (young: AUC=0.82, middle: AUC=0.83, old: AUC=0.85).
CONCLUSION
Age as a factor affecting microbial composition should be considered in the application of gut microbiota to predict the risk of CRC.
Topics: Humans; Gastrointestinal Microbiome; Colorectal Neoplasms; Bacteria; Microbiota; Aging
PubMed: 37548332
DOI: 10.1002/cam4.6414 -
Microbial Genomics Jul 2023is prevalent in the intestines of humans and animals, and ambiguities have been reported regarding its relations with the development of diseases and host well-being....
is prevalent in the intestines of humans and animals, and ambiguities have been reported regarding its relations with the development of diseases and host well-being. We postulate the ambiguities of its function in different cases may be attributed to strain-level variability of genomic features of . We performed comparative genomic and pathogenicity prediction analysis on 152 filtered high-quality genomes, including 4 genomes of strains isolated from healthy adults in this study. The mean G+C content of genomes of was 42.73±0.33 mol%, and the mean genome size was 3.46±0.34 Mbp. Genome-wide evolutionary analysis revealed genomes were divided into three major phylogenetic clusters. Pan-core genome analysis revealed that there was a total of 28 072 predicted genes, and the core genes, soft-core genes, shell genes and cloud genes accounted for 3.74 % (1051/28 072), 1.75 % (491/28 072), 9.88 % (2774/28 072) and 84.63 % (23 756/28 072) of the total genes, respectively. The small proportion of core genes reflected the wide divergence among strains. We found certain coding sequences with determined health benefits (such as vitamin production and arsenic detoxification), whilst some had an implication of health adversity (such as sulfide dehydrogenase subunits). The functions of the majority of core genes were unknown. The most widespread genes functioning in antibiotic resistance and virulence are (tetracycline-resistance gene, present in 75 strains) and (capsular polysaccharide biosynthesis protein Cps4J encoding gene, detected in 3 genomes), respectively. Our results revealed genomic divergence and the existence of certain safety-relevant factors of . This study provides new insights for understanding the genomic features and health relevance of , and raises concerns regarding predicted prevalent pathogenicity and antibiotic resistance among most of the strains.
Topics: Adult; Animals; Humans; Ruminococcus; Phylogeny; Clostridiales; Genomics
PubMed: 37486746
DOI: 10.1099/mgen.0.001071