•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.
Colorectal cancer is one of the most common malignancies worldwide. Recently, a novel circular RNA, ciRS-7, was proposed to be a potential miR-7 sponge. As miR-7, a putative tumor-suppressor, ...regulates the expression of several important drivers of colorectal cancer, we analyzed the clinical significance of ciRS-7 in colorectal cancer patients.
Initially, we evaluated the expression levels of ciRS-7 in a training cohort comprising of 153 primary colorectal cancer tissues and 44 matched normal mucosae. We subsequently confirmed its clinical relevance in an independent validation cohort (
= 165), and evaluated the effect of ciRS-7 on miR-7, and its target genes EGFR and RAF1. Functional analyses were performed in cell lines and an animal model to support clinical findings.
Our data revealed that ciRS-7 was significantly upregulated in colorectal cancer tissues compared with matched normal mucosae (
= 0.0018), and its overexpression was associated with poor patient survival (
= 0.0224 and 0.0061 in the training and validation cohorts, respectively). Multivariate survival analysis revealed that ciRS-7 emerged as an independent risk factor for overall survival (
= 0.0656 and 0.0324 in the training and validation cohorts, respectively). Overexpression of ciRS-7 in HCT116 and HT29 cells led to the blocking of miR-7 and resulted in a more aggressive oncogenic phenotype, and ciRS-7 overexpression permitted the inhibition of miR-7 and subsequent activation of EGFR and RAF1 oncogenes.
CiRS-7 is a promising prognostic biomarker in colorectal cancer patients and may serve as a therapeutic target for reducing EGFR-RAF1 activity in colorectal cancer patients.
.
Background
Slow transit constipation (STC) is a type of functional constipation in which colon transit time is extended as a result of a reduction in the high amplitude of colon contraction activity. ...The utility of gut microbiome and metabolite characteristics in patients with STC is rarely studied. Short-chain fatty acids (SCFAs) enhance colonic fluid and sodium absorption and thus may aggravate the symptoms of STC. However, the content and role of SCFAs in constipation patients are not clear. We speculate that gut microbiome and SCFAs in the colon of STC patients may be abnormal and linked to the underlying mechanism of STC.
Methods
This observational study is registered at ClinicalTrials.gov (NCT02984969). The high-throughput sequencing was used to analyze the diversity and composition of fecal microbial communities. Gas chromatography–mass spectrometry (GC–MS) was used to determine the properties and concentrations of the SCFAs in the two groups.
Results
The Shannon diversity and Simpson diversity of the gut microbiome were significantly greater in the STC group than the control group. The two groups also showed significant differences in the species composition of the gut microbiome at different classification levels. The results of GC–MS showed that the acetate concentrations in the STC group were significantly reduced compared with the control group, but the other five types of SCFAs and total SCFAs showed no significant difference between groups. ROC curve analyses revealed that the AUC of Acetate (AUC = 0.758) was higher than Propionate (AUC = 0.660). The largest AUC of gut microbiome for predicting STC was Prevotella (AUC = 0.807). Correlation analysis showed a positive correlation between the concentration of Ruminococcus and Disease history (rs = 0.519). Meanwhile, a positive correlation between the concentration of Roseburia and Acetate (rs = 0.606) or Butyrate (rs = 0.543) was found.
Conclusion
We found significant differences between the STC and control groups in the main components of the gut microbiome, with greater diversity in the STC group and differences between the groups in species composition at different classification levels. These different microbiome and metabolite may be valuable biomarkers for STC.
Mounting evidence indicates that obesity may be associated with the risk of colorectal cancer (CRC). To conduct a systematic review of prospective studies assessing the association of obesity with ...the risk of CRC using meta-analysis.
Relevant studies were identified by a search of MEDLINE and EMBASE databases before January 2012, with no restrictions. We also reviewed reference lists from retrieved articles. We included prospective studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the association between general obesity measured using body mass index (BMI) or central obesity measured using waist circumference (WC) and the risk of colorectal, colon, or rectal cancer. Approximately 9, 000, 000 participants from several countries were included in this analysis. 41 studies on general obesity and 13 studies on central obesity were included in the meta-analysis. The pooled RRs of CRC for the obese vs. normal category of BMI were 1.334 (95% CI, 1.253-1.420), and the highest vs. lowest category of WC were 1.455 (95% CI, 1.327-1.596). There was heterogeneity among studies of BMI (P<0.001) but not among studies of WC (P=0.323).
Both of general and central obesity were positively associated with the risk of CRC in this meta-analysis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The ketogenic diet (KD) is a high-fat, adequate-protein, and very-low-carbohydrate diet regimen that mimics the metabolism of the fasting state to induce the production of ketone bodies. The KD has ...long been established as a remarkably successful dietary approach for the treatment of intractable epilepsy and has increasingly garnered research attention rapidly in the past decade, subject to emerging evidence of the promising therapeutic potential of the KD for various diseases, besides epilepsy, from obesity to malignancies. In this review, we summarize the experimental and/or clinical evidence of the efficacy and safety of the KD in different diseases, and discuss the possible mechanisms of action based on recent advances in understanding the influence of the KD at the cellular and molecular levels. We emphasize that the KD may function through multiple mechanisms, which remain to be further elucidated. The challenges and future directions for the clinical implementation of the KD in the treatment of a spectrum of diseases have been discussed. We suggest that, with encouraging evidence of therapeutic effects and increasing insights into the mechanisms of action, randomized controlled trials should be conducted to elucidate a foundation for the clinical use of the KD.
Intestinal dysmotility is common in many diseases and is correlated with gut microbiota dysbiosis and systemic inflammation. Functional constipation (FC) is the most typical manifestation of ...intestinal hypomotility and reduces patients’ quality of life. Some studies have reported that fecal micriobiota transplantation (FMT) may be an effective and safe therapy for FC as it corrects intestinal dysbiosis. This study was conducted to evaluate how FMT remodels the gut microbiome and to determine a possible correlation between certain microbes and clinical symptoms in constipated individuals. Data were retrospectively collected on 18 patients who underwent FMT between January 1, 2019 and June 30, 2020. The fecal bacterial genome was detected by sequencing the V3–V4 hypervariable regions of the 16S rDNA gene. Fecal short chain fatty acids (SCFAs) were detected by gas chromatography-mass spectrometry, and serum inflammatory factor concentrations were detected via enzyme-linked immunosorbent assay. Comparing the changes in fecal microbiome compositions before and after FMT revealed a significant augmentation in the alpha diversity and increased abundances of some flora such as Clostridiales,
Fusicatenibacter
, and
Paraprevotella
. This was consistent with the patients experiencing relief from their clinical symptoms. Abundances of other flora, including
Lachnoanaerobaculum
, were decreased, which might correlate with the severity of patients’ constipation. Although no differences were found in SCFA production, the butyric acid concentration was correlated with both bacterial alterations and clinical symptoms. Serum IL-8 levels were significantly lower after FMT than at baseline, but IL-4, IL-6, IL-10, and IL-12p70 levels were not noticeably changed. This study showed how FMT regulates the intestinal microenvironment and affects systemic inflammation in constipated patients, providing direction for further research on the mechanisms of FMT. It also revealed potential microbial targets for precise intervention, which may bring new breakthroughs in treating constipation.
To conduct a systematic review of prospective studies assessing the association of vitamin D intake or blood levels of 25-hydroxyvitamin D 25(OH)D with the risk of colorectal cancer using ...meta-analysis.
Relevant studies were identified by a search of MEDLINE and EMBASE databases before October 2010 with no restrictions. We included prospective studies that reported relative risk (RR) estimates with 95% CIs for the association between vitamin D intake or blood 25(OH)D levels and the risk of colorectal, colon, or rectal cancer. Approximately 1,000,000 participants from several countries were included in this analysis.
Nine studies on vitamin D intake and nine studies on blood 25(OH)D levels were included in the meta-analysis. The pooled RRs of colorectal cancer for the highest versus lowest categories of vitamin D intake and blood 25(OH)D levels were 0.88 (95% CI, 0.80 to 0.96) and 0.67 (95% CI, 0.54 to 0.80), respectively. There was no heterogeneity among studies of vitamin D intake (P = .19) or among studies of blood 25(OH)D levels (P = .96). A 10 ng/mL increment in blood 25(OH)D level conferred an RR of 0.74 (95% CI, 0.63 to 0.89).
Vitamin D intake and blood 25(OH)D levels were inversely associated with the risk of colorectal cancer in this meta-analysis.
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.
In the past decades, the Hippo signaling pathway has been delineated and shown to play multiple roles in the control of organ size in both Drosophila and mammals. In mammals, the Hippo pathway is a ...kinase cascade leading from Mst1/2 to YAP and its paralog TAZ. Several studies have demonstrated that YAP/TAZ is a candidate oncogene and that other members of the Hippo pathway are tumor suppressive genes. The dysregulation of the Hippo pathway has been observed in a variety of cancers. This review chronicles the recent progress in elucidating the function of Hippo signaling in tumorigenesis and provide a rich source of potential targets for cancer therapy.
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.
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