•Probiotics supplementation slowed weight gain in both the high-fat diet (HFD) and high-sucrose diet (HCD) groups.•An HFD is more likely to reduce gut microbiota diversity, whereas an HCD is more ...likely to alter the bacterial composition related to obesity.•Probiotics treatment can mitigate diet-induced obesity partly through modulating intestinal microbiota, especially in HCD-induced obesity.
Gut microbiota plays a crucial role in host energy homeostasis, which is affected by both high-fat diets (HFDs) and high-sucrose diets (HCDs). Probiotics treatment can effectively modulate intestinal microbiota. However, it remains unclear whether probiotics can effectively improve HFD- and HCD-induced microbiota dysbiosis.
Mice were fed either an HFD, HCD, or normal diet for 13 wk and administered probiotics during the last 4 wk of the diet. Fecal and cecal samples were collected and analyzed by high-throughput 16S ribosomal RNA sequencing.
Body weight increased more in the HFD group compared with the HCD group. Probiotics supplementation slowed weight gain in both the HFD and HCD groups. Both the HFD and HCD reduced microbial diversity, abundance of butyric acid–producing bacteria, and some other beneficial bacteria, including Lactobacillus, Clostridium sensu stricto, Prevotella, and Alloprevotella, but increased conditional pathogenic bacteria, such as Bacteroides, Alistipes, and Anaerotruncus. Probiotics markedly restored the proportions of bacteria affected in the HFD and HCD groups and increased the abundance of microbiota negatively associated with obesity, including Bifidobacterium, Lactococcus, and Akkermansia. In addition, Oscillibacter, Escherichia/Shigella, Acinetobacter, and Blautia significantly increased in the HCD group; Allobaculum, Olsenella, and Ruminococcus were significantly changed in the HFD group. HCD-induced microbiota dysbiosis was more susceptible to probiotics treatment compared with the HFD.
Probiotics treatment can mitigate diet-induced obesity partly through modulating intestinal microbiota, especially in HCD-induced obesity.
The human gastrointestinal tract harbors a complex and abundant microbial community that can reach levels as high as 10
13
–10
14
microorganisms in the colon. These microorganisms are essential to a ...host’s well-being in terms of nutrition and mucosa immunity. However, numerous studies have also implicated members of the colonic microbiota in the development of colorectal cancer (CRC). While CRC involves a genetic component where damaged DNA and genetic instability initiates a malignant transformation, environmental factors can also contribute to the onset of CRC. Furthermore, considering the constant exposure of the colonic mucosa to the microbiome and/or its metabolites, the mucosa has long been proposed to contribute to colon tumorigenesis. However, the mechanistic details of these associations remain unknown. Fortunately, due to technical and conceptual advances, progress in characterizing the taxonomic composition, metabolic capacity, and immunomodulatory activity of human gut microbiota have been made, thereby elucidating its role in human health and disease. Furthermore, the use of experimental animal models and clinical/epidemiological studies of environmental etiological factors has identified a correlation between gut microbiota composition and gastrointestinal cancers. Bacteria continuously stimulate activated immunity in the gut mucosa and also contribute to the metabolism of bile and food components. However, the highest levels of carcinogen production are also associated with gut anaerobic bacteria and can be lowered with live lactobacilli supplements. In this review, evidence regarding the relationship between microbiota and the development of CRC will be discussed, as well as the role for microbial manipulation in affecting disease development.
Accumulating evidence suggests that ketogenic diets (KDs) mediate the rise of circulating ketone bodies and exert a potential anti-inflammatory effect; however, the consequences of this unique diet ...on colitis remain unknown. We performed a series of systematic studies using a dextran sulfate sodium (DSS) animal model of inflammatory colitis. Animals were fed with a KD, low-carbohydrate diet (LCD), or normal diet (ND). Germ-free mice were utilized in validation experiments. Colon tissues were analyzed by transcriptome sequencing, RT2 profiler PCR array, histopathology, and immunofluorescence. Serum samples were analyzed by metabolic assay kit. Fecal samples were analyzed by 16S rRNA gene sequencing, liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. We observed that KD alleviated colitis by altering the gut microbiota and metabolites in a manner distinct from LCD. Quantitative diet experiments confirmed the unique impact of KD relative to LCD with a reproducible increase in Akkermansia, whereas the opposite was observed for Escherichia/Shigella. After colitis induction, the KD protected intestinal barrier function, and reduced the production of RORγt
CD3
group 3 innate lymphoid cells (ILC3s) and related inflammatory cytokines (IL-17α, IL-18, IL-22, Ccl4). Finally, fecal microbiota transplantation into germ-free mice revealed that the KD- mediated colitis inhibition and ILC3 regulation were dependent on the modification of gut microbiota. Taken together, our study presents a global view of microbiome-metabolomics changes that occur during KD colitis treatment, and identifies the regulation of gut microbiome and ILC3s as novel targets involving in IBD dietary therapy.
Gut microbiota dysbiosis has been considered to be an important risk factor that contributes to coronary artery disease (CAD), but limited evidence exists about the involvement of gut microbiota in ...the disease. Our study aimed to characterize the dysbiosis signatures of gut microbiota in coronary artery disease. The gut microbiota represented in stool samples were collected from 70 patients with coronary artery disease and 98 healthy controls. 16S rRNA sequencing was applied, and bioinformatics methods were used to decipher taxon signatures and function alteration, as well as the microbial network and diagnostic model of gut microbiota in coronary artery disease. Gut microbiota showed decreased diversity and richness in patients with coronary artery disease. The composition of the microbial community changed; Escherichia-Shigella false discovery rate (FDR = 7.5*10
and Enterococcus (FDR = 2.08*10
) were significant enriched, while Faecalibacterium (FDR = 6.19*10
), Subdoligranulum (FDR = 1.63*10
), Roseburia (FDR = 1.95*10
), and Eubacterium rectale (FDR = 2.35*10
) were significant depleted in the CAD group. Consistent with the taxon changes, functions such as amino acid metabolism, phosphotransferase system, propanoate metabolism, lipopolysaccharide biosynthesis, and protein and tryptophan metabolism were found to be enhanced in CAD patients. The microbial network revealed that Faecalibacterium and Escherichia-Shigella were the microbiotas that dominated in the healthy control and CAD groups, respectively. The microbial diagnostic model based on random forest also showed probability in identifying those who suffered from CAD. Our study successfully identifies the dysbiosis signature, dysfunctions, and comprehensive networks of gut microbiota in CAD patients. Thus, modulation targeting the gut microbiota may be a novel strategy for CAD treatment.
Emerging research has revealed regulation of colorectal cancer metabolism by bacteria.
(
) plays a crucial role in the development of colorectal cancer, however, whether
infection modifies metabolism ...in patients with colorectal cancer remains unknown. Here, LC-MS/MS-based lipidomics identified the upregulation of cytochrome P450 monooxygenases, primarily CYP2J2, and their mediated product 12,13-EpOME in patients with colorectal cancer tumors and mouse models, which increased the invasive and migratory ability of colorectal cancer cells
and
by regulating the epithelial-mesenchymal transition (EMT). Metagenomic sequencing indicated a positive correlation between increased levels of fecal
and serum 12,13-EpOME in patients with colorectal cancer. High levels of CYP2J2 in tumor tissues also correlated with high
levels and worse overall survival in patients with stage III/IV colorectal cancer. Moreover,
was found to activate TLR4/AKT signaling, downregulating Keap1 and increasing NRF2 to promote transcription of CYP2J2. Collectively, these data identify that
promotes EMT and metastasis in colorectal cancer by activating a TLR4/Keap1/NRF2 axis to increase CYP2J2 and 12,13-EpOME, which could serve as clinical biomarkers and therapeutic targets for
-infected patients with colorectal cancer. SIGNIFICANCE: This study uncovers a mechanism by which
regulates colorectal cancer metabolism to drive metastasis, suggesting the potential biomarker and therapeutic utility of the CYP2J2/12,13-EpOME axis in
-infected patients.
Recent reports have suggested that multiple factors such as host genetics, environment and diet can promote the progression of healthy mucosa towards sporadic colorectal carcinoma. Accumulating ...evidence has additionally associated intestinal bacteria with disease initiation and progression. In order to examine and analyze the composition of gut microbiota in the absence of confounding influences, we have established an animal model of 1, 2-dimethylhydrazine (DMH)-induced colon cancer. Using this model, we have performed pyrosequencing of the V3 region of the 16S rRNA genes in this study to determine the diversity and breadth of the intestinal microbial species. Our findings indicate that the microbial composition of the intestinal lumen differs significantly between control and tumor groups. The abundance of Firmicutes was elevated whereas the abundance of Bacteroidetes and Spirochetes was reduced in the lumen of CRC rats. Fusobacteria was not detected in any of the healthy rats and there was no significant difference in observed Proteobacteria species when comparing the bacterial communities between our two groups. Interestingly, the abundance of Proteobacteria was higher in CRC rats. At the genus level, Bacteroides exhibited a relatively higher abundance in CRC rats compared to controls (14.92% vs. 9.22%, p<0.001). Meanwhile, Prevotella (55.22% vs. 26.19%), Lactobacillus (3.71% vs. 2.32%) and Treponema (3.04% vs. 2.43%), were found to be significantly more abundant in healthy rats than CRC rats (p<0.001, respectively). We also demonstrate a significant reduction of butyrate-producing bacteria such as Roseburia and Eubacterium in the gut microbiota of CRC rats. Furthermore, a significant increase in Desulfovibrio, Erysipelotrichaceae and Fusobacterium was also observed in the tumor group. A decrease in probiotic species such as Ruminococcus and Lactobacillus was likewise observed in the tumor group. Collectively, we can conclude that a significant difference in intestinal bacterial flora exists between healthy rats and CRC rats.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
MicroRNA-21 (miR-21) is overexpressed in most inflammatory diseases, but its physiological role in gut inflammation and tissue injury is poorly understood. The goal of this work is to understand the ...role of miR-21 in colitis and damage progression of intestine in a genetically modified murine model.
Experimental colitis was induced in miR-21 KO and wild-type (WT) mice by 3.5% dextran sulphate sodium (DSS) administration for 7 days. Disease activity index(DAI), blood parameters, intestinal permeability, histopathologic injury, cytokine and chemokine production, and epithelial cells apoptosis were examined in colons of miR-21 KO and WT mice.
miR-21 was overexpressed in intestine of inflammatory bowel diseases (IBD) and acute intestinal obstruction (AIO) patients when compared with normal intestinal tissues. Likewise, miR-21 was up-regulated in colon of IL-10 KO mice when compared with control mice. WT mice rapidly lost weight and were moribund 5 days after treatment with 3.5% DSS, while miR-21 KO mice survived for at least 6 days. Elevated leukocytes and more severe histopathology were observed in WT mice when compared with miR-21 KO mice. Elevated levels of TNF-α and macrophage inflammatory protein-2(MIP-2) in colon culture supernatants from WT mice exhibited significant higher than miR-21 KO mice. Furthermore, CD3 and CD68 positive cells, intestinal permeability and apoptosis of epithelial cells were significantly increased in WT mice when compared with miR-21 KO mice. Finally, we found that miR-21 regulated the intestinal barrier function through modulating the expression of RhoB and CDC42.
Our results suggest that miR-21 is overexpressed in intestinal inflammation and tissue injury, while knockout of miR-21 in mice improve the survival rate in DSS-induced fatal colitis through protecting against inflammation and tissue injury. Therefore, attenuated expression of miR-21 in gut may prevent the onset or progression of inflammatory bowel disease in patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Treatment of rectovaginal fistulas (RVFs) is extremely difficult. No standard surgical procedure is accepted worldwide. The aim of this article was to evaluate a minimally invasive ...procedure for the repair of mid-low rectovaginal fistula.
Methods
This is a retrospective review of 17 patients who underwent minimally invasive surgery for the repair of mid-low rectovaginal fistulas (located in the lower or middle one-third of the vaginal wall) at our center between August 2016 and October 2018. The anal approach was adopted for 12 patients: 6 patients were treated directly by rectal mucosal advancement flap (RMAF) with transanal endoscopic surgery (TES), while the other 6 patients underwent initial TES exploration followed by RMAF procedure under direct vision. The vaginal approach was adopted for 5 patients: 3 patients were treated under TES directly and the other 2 were treated under direct vision after initial TES exploration. A total of 9 (52.94%) patients received diverting ileostomy—5 anal approach patients and 4 vaginal approach patients.
Results
Median age of the patients was 46 years (range 10–76 years), and median BMI was 21.9 (range 17.9–28.1). Median operative time was 75 min (range 60–120 min), and median duration of postoperative hospital stay was 8 days (range 6–15 days). Recurrence was seen in 3/12 anal approach patients vs. 0/5 vaginal approach patients. Both the median preoperative and the median postoperative Wexner score were 0 (range 0–2). The median follow-up time was 8 months (range 2–24). No severe complications occurred in any patient.
Conclusion
The TES procedure for the treatment of mid-low rectovaginal fistulas avoids any incision of the abdomen and perineal area and appears to be a safe and feasible procedure. This minimally invasive technique is still evolving and is likely to gain wide acceptance in the near future.
This study was designed to mainly evaluate the anti-infective effects of perioperative probiotic treatment in patients receiving confined colorectal cancer (CRC) respective surgery. From November ...2011 to September 2012, a total of 60 patients diagnosed with CRC were randomly assigned to receive probiotic (n = 30) or placebo (n = 30) treatment. The operative and post-operative clinical results including intestinal cleanliness, days to first - flatus, defecation, fluid diet, solid diet, duration of pyrexia, average heart rate, length of intraperitoneal drainage, length of antibiotic therapy, blood index changes, rate of infectious and non-infectious complications, postoperative hospital stay, and mortality were investigated. The patient demographics were not significantly different (p > 0.05) between the probiotic treated and the placebo groups. The days to first flatus (3.63 versus 3.27, p = 0.0274) and the days to first defecation (4.53 versus 3.87, p = 0.0268) were significantly improved in the probiotic treated patients. The incidence of diarrhea was significantly lower (p = 0.0352) in probiotics group (26.67%, 8/30) compared to the placebo group (53.33%, 16/30). There were no statistical differences (p > 0.05) in other infectious and non-infectious complication rates including wound infection, pneumonia, urinary tract infection, anastomotic leakage, and abdominal distension. In conclusion, for those patients undergoing confined CRC resection, perioperative probiotic administration significantly influenced the recovery of bowel function, and such improvement may be of important clinical significance in reducing the short-term infectious complications such as bacteremia.
Re-expression of an embryonic morphogen, Nodal, has been seen in several types of malignant tumours. By far, studies about Nodal's role in colorectal cancer (CRC) remain limited. Ferroptosis is ...essential for CRC progression, which is caused by cellular redox imbalance and characterized by lipid peroxidation. Herein, we observed that Nodal enhanced CRC cell's proliferative rate, motility, invasiveness, and epithelial-mesenchymal transition (EMT) in vivo and in vitro. Notably, Nodal overexpression induced monounsaturated fatty acids synthesis and increased the lipid unsaturation level. Nodal knockdown resulted in increased CRC cell lipid peroxidation. Stearoyl-coenzyme A desaturase 1 (SCD1) inhibition at least partially abolished the resistance of Nodal-overexpressing cells to RSL3-induced ferroptosis. Mechanistically, SCD1 was transcriptionally up-regulated by Smad2/3 pathway activation in response to Nodal overexpression. Significant Nodal and SCD1 up-regulation were observed in CRC tissues and were associated with CRC metastasis and poor clinical outcomes. Furthermore, bovine serum albumin nanoparticles/si-Nodal nanocomplexes targeting Nodal had anti-tumour effects on CRC progression and metastasis. This research elucidated the role of Nodal in CRC development and revealed a potential gene-based therapeutic strategy targeting Nodal for improving CRC treatment.
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