Gut microbiota alterations in colorectal adenoma-carcinoma sequence based on 16S rRNA gene sequencing: A systematic review and meta-analysis.

BACKGROUND: Most sporadic colorectal cancers (CRC) develop through the adenoma-carcinoma sequence. While dysbiosis of the intestinal flora contributes to CRC's pathogenesis, precise microbial taxa closely associated with the colorectal adenoma-carcinoma sequence remain elusive. This meta-analysis aimed to summarize the features of intestinal flora in patients with AD and CRC. METHODS: PubMed, Embase, Cochrane Library, and Web of Science were searched for case-control studies comparing the relative abundance of gut microbiota in the feces of patients with AD, CRC, and healthy controls (HC) from inception to January 2024. The weighted mean difference (WMD) with a 95 % confidence interval (CI) was used to display the results. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the entailed literature. Publication bias was evaluated with the Egger's and Begg's tests. RESULTS: Eleven studies were included, involving 477 CRC patients, 628 AD patients, and 864 healthy controls. Compared with HC, the patients with AD had a significantly lower Chao 1 index (WMD = -30.17, 95 % CI [-41.10, -19.23], P < 0.001) and Shannon index (WMD = -0.11 95 % CI [-0.18, -0.04], P = 0.002). Compared with AD, the CRC patients had a significantly higher Chao1 index (WMD = 22.09, 95 % CI [7.59, 36.00], P = 0.003) and Shannon index (WMD = 0.08, 95 % CI [0.00, 0.15], P = 0.037). Enterobacteriaceae (WMD = 0.03 95 % CI [0.00,0.05], P = 0.047; WMD = 0.02 95 % CI [0.00,0.04], P = 0.027) significantly increased in the order of Control-AD-CRC, while that of Blautia (WMD = -0.00 95 % CI [-0.01, -0.00], P = 0.001; WMD = -0.00 95 % CI [-0.00, -0.00], P = 0.002) was reduced. Compared with HC, the relative abundance of Proteobacteria (WMD = 0.05 95 % CI [0.03,0.07], P < 0.001), Fusobacteria (WMD = 0.02 95 % CI [0.00,0.03], P = 0.042), Streptococcaceae (WMD = 0.03 95 % CI [0.01,0.05], P = 0.017), Prevotellaceae (WMD = 0.02 95 % CI [0.00,0.04], P = 0.040), and Escherichia-Shigella (WMD = 0.06 95 % CI [0.01, 0.11], P = 0.021) was enriched in the CRC group. The relative abundance of Alistipes (WMD = 0.00 95 % CI [0.00,0.01], P = 0.032) and Streptococcus (WMD = 0.00 95 % CI [0.00,0.00], P = 0.001) was increased in the AD vs HC. The relative abundance of Firmicutes (WMD = -0.07 95 % CI [-0.12, -0.03], P = 0.003), Bifidobacteria (WMD = -0.03 95 % CI [-0.05, -0.01], P = 0.016), and Klebsiella (WMD = -0.01 95 % CI [-0.01, -0.00], P = 0.001) was decreased in the CRC vs HC. Compared with AD, the relative abundance of Firmicutes (WMD = -0.04 95 % CI [-0.07, -0.02], P = 0.002), Peptostreptococcaceae (WMD = -0.03 95 % CI [-0.05, -0.00], P = 0.021), Lachnospiraceae (WMD = -0.04 95 % CI [-0.08,-0.00], P = 0.037), Ruminococcaceae (WMD = -0.06 95 % CI [-0.09,-0.03], P < 0.001), Faecalibacterium (WMD = -0.01 95 % CI [-0.02, -0.01], P = 0.001), and Lachnoclostridium (WMD = -0.02 95 % CI [-0.03, -0.00], P = 0.040) was decreased in the CRC group, while Proteobacteria (WMD = 0.04 95 % CI [0.02,0.05], P < 0.001) was increased. CONCLUSIONS: The dysbiosis characterized by reduced levels of short-chain fatty acid (SCFA)-producing bacteria, decreased anti-inflammatory bacteria, increased pro-inflammatory bacteria, and an elevation of bacteria with cytotoxic effects damaging to DNA may represent the specific microbial signature of colorectal adenoma/carcinoma. Further research is required to elucidate the mechanisms by which gut dysbiosis leads to the progression from AD to CRC and to explore the potential of specific microbiota markers in clinical treatment and non-invasive screening.

MAFLD with central obesity is associated with increased risk of colorectal adenoma and high-risk adenoma.

OBJECTIVE: To analyze the risk factors associated with colorectal adenoma and to investigate the associations of metabolism-related fatty liver disease (MAFLD) with obesity, colorectal adenoma and high-risk adenoma. METHODS: A total of 1395 subjects were enrolled and divided into a colorectal adenoma group (593 subjects) and a control group (802 subjects) according to the inclusion and exclusion criteria. The characteristics of patients in the colorectal adenoma group and the control group were compared by the chi-square test. Univariate and multivariate logistic analyses were used to analyze independent risk factors and associations with different MAFLD subtypes. Colorectal adenoma characteristics and the proportion of patients with high-risk colorectal adenoma were also compared. RESULTS: High-density lipoprotein (HDL-C) was significantly lower in patients in the colorectal adenoma group than in those in the control group (P < 0.001). Logistic regression analysis revealed that age, obesity status, central obesity status, hypertension status, diabetes status, fatty liver status, smoking history, BMI, waist circumference, triglyceride level, HDL-C level, fasting blood glucose level and degree of hepatic steatosis were all independent risk factors for colorectal adenoma. Notably, MAFLD was associated with a significantly increased risk of colorectal adenoma in patients with central obesity (P < 0.001). In addition, obesity, central obesity, diabetes, fatty liver and degree of hepatic steatosis were all shown to be independent risk factors for high-risk colorectal adenoma. In addition, a greater proportion of MAFLD patients with central obesity than those without central obesity had high-risk colorectal adenoma. CONCLUSION: MAFLD and central obesity are independently associated with the development of colorectal adenoma. MAFLD with central obesity is associated with an increased risk of colorectal adenoma and high-risk adenoma.

Mosapride Stabilizes Intestinal Microbiota to Reduce Bacterial Translocation and Endotoxemia in CCl4-Induced Cirrhotic Rats.

BACKGROUND: Impaired intestinal motility may lead to the disruption of gut microbiota equilibrium, which in turn facilitates bacterial translocation (BT) and endotoxemia in cirrhosis. We evaluated the influence of mosapride, a prokinetic agent, on BT and DNA fingerprints of gut microbiota in cirrhotic rats. METHODS: A rat model of cirrhosis was set up via subcutaneous injection of carbon tetrachloride (CCl4). The portal pressure, liver and intestinal damage, plasma endotoxin, BT, and intestinal transit rate (ITR) of cirrhotic rats were determined. Fecal DNA fingerprints were obtained by ERIC-PCR. The expressions of tight junction proteins were evaluated by western blotting. RESULTS: Mosapride treatment to cirrhotic rats significantly reduced the plasma endotoxin level and incidence of BT, accompanied by increased ITR. Cirrhotic rats (including those treated with mosapride) suffered from BT exhibited significantly lower ITR than those who are free of BT. Pearson coefficient indicated a significant and negative correlation between the plasma endotoxin level and ITR. The genomic fingerprints of intestinal microbiota from the three groups fell into three distinctive clusters. In the mosapride-treated group, Shannon's index was remarkably increased compared to the model group. Significantly positive correlation was detected between Shannon's index and ITR. Mosapride did not improve hepatic and intestinal damages and ileal expressions of occludin and ZO-1. CONCLUSIONS: Mosapride significantly increases intestinal motility in cirrhotic rats, thus to recover the disordered intestinal microbiota, finally resulting in decreased plasma endotoxin and BT.

[Effect of Busheng Huoxue Capsule on the quality of life of primary osteoporosis senile males].

OBJECTIVE: To investigate the effect of Busheng Huoxue Capsule (BHC) on the quality of life (QOL) in senile male osteoporosis (OP) patients, and to explore its mechanisms. METHODS: Totally 200 senile primary OP patients were randomly assigned to two groups according to random digit table method, 100 in each group. Patients in the treatment group took BHC plus caltrate-D (600 mg CaCO3), while those in the control group took alendronate (70 mg per week) plus caltrate-D. The therapeutic course was 12 months for all. Chinese medical symptom score and quality of life (QUALEFFO-41) score, bone mineral density (BMD) of lumbar vertebra (L2 -L4) and left femoral neck were compared between the two groups before and after treatment. Serum free testosterone (FT) and estradiol (E2) were also measured. RESULTS: Chinese medical symptom scores and QUALEFFO-41 scores, serum FT and E2 levels increased in the two groups after treatment (P < 0.05, P < 0.01). The therapeutic effect was superior in the treatment group (P < 0.05, P < 0.01). After treatment the BMD of lumbar vertebra (L2 -L4) and the left femoral neck were somewhat improved (P < 0.05), but with no statistical difference between the two groups (P > 0.05). CONCLUSION: BHC could effectively improve the QOL of senile male OP patients, which might be correlated with elevating the BMD levels and regulating the levels of sex hormones.

Physicochemical property changes of Dendrobium officinale leaf polysaccharide LDOP-A and it promotes GLP-1 secretion in NCI-H716 cells by simulated saliva-gastrointestinal digestion.

A polysaccharide LDOP-A with a molecular weight of 9.9 kDa was isolated and purified from Dendrobium officinale leaves by membrane separation, cellulose column, and dextran gel column. The Smith degradable products, methylation products, and nuclear magnetic resonance analysis showed that LDOP-A may be composed of →4)-Glc-(1→, →3,6)-Man-(1→, and →6)-Glc-(1→sugar residues. In vitro, simulated digestion assays showed that LDOP-A could be partially digested in the stomach and small intestine, and produced a large amount of acetic acid and butyric acid during colonic fermentation. Further cell experiment results illustrated that LDOP-A-I (LDOP-A digested by gastrointestinal tract) could induce glucagon-like peptide-1 (GLP-1) secretion in NCI-H716 cells without showing any cytotoxicity.

Comparing the Influences of Metformin and Berberine on the Intestinal Microbiota of Rats With Nonalcoholic Steatohepatitis.

BACKGROUND/AIM: High-fat diets induce shifts in the gut microbial community structure in patients or animals with non-alcoholic steatohepatitis (NASH). The objective of this study was to investigate the influence of metformin (MET) and berberine (BER) on the intestinal microbiota of rats with NASH. MATERIALS AND METHODS: Forty specific pathogen-free male Sprague-Dawley rats were randomized into 4 groups. Model rats were fed high-fat diets to create NASH models. MET or BER rats were administrated MET or BER, respectively, at the onset of induction of NASH. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol, and triglycerides were examined. Plasma endotoxin levels were measured using the turbidimetric endotoxin assay. The incidence of bacterial translocation describes the passage of bacteria of the gastrointestinal tract through the intestinal mucosa barrier to mesenteric lymph nodes and other organs. Hematoxylin and eosin and oil red O staining were used for histopathological analysis. High throughput 16S rRNA sequencing was carried out for analyzing the composition of intestinal microbiota. RESULTS: High-fat diets caused NASH after 16-week induction. Administration of MET and BER ameliorated NASH by attenuating hepatic steatosis and inflammation and decreasing the plasma levels of endotoxin. MET and BER restored the composition of the intestinal microbiota disrupted by NASH. Both MET and BER altered the abundance of Atopobiaceae, Brevibacterium, Christensenellaceae, Coriobacteriales, Papillibacter, Pygmaiobacter, and Rikenellaceae RC9 in rats with NASH. The screened intestinal microbiota may be responsible for the improvement in fat accumulation and glucose metabolism. CONCLUSION: MET and BER demonstrated beneficial effects on the intestinal microbiota, which was disturbed in NASH. This finding may explain the functional mechanism of MET and BER in NASH.

The influence of mosapride on gut microbiota of carbon tetrachloride-induced cirrhosis rats based on 16S rRNA gene sequencing.

BACKGROUND: Mosapride significantly improves intestinal motility in liver cirrhosis, ultimately leading to the reduction in plasma endotoxin levels and bacterial translocation. OBJECTIVES: To investigate the effects of mosapride on intestinal microecology in cirrhotic rats and its potential mechanisms. MATERIAL AND METHODS: Forty-five healthy male Sprague-Dawley rats that were pathogen-free (weight 200-220 g) were randomly divided into a control group (n = 15), model group (n = 15) and mosapride group (n = 15). Then, the pathological changes in the liver and intestine were determined through tissue staining and using transmission electron microscope (TEM). Bacterial translocation was examined. High throughput 16S rRNA sequencing was performed to determine the changes of gut microbiota in each group. RESULTS: Compared with the model group, mosapride treatment induced no attenuation in hepatic morphology and pathology changes. The TEM indicated no differences in intestinal structure in both groups. There was a significant decline in the rate of gut microbiota translocation in the mosapride group compared with the model group. There were intestinal microbiota changes in the mosapride group compared with that of the model group, including Bacteroidetes, Prevotellaceae, Alloprevotella, Ruminiclostridium, Negativicutes, Selenomonadales, Veillonellaceae, Anaerovibrio, Campylobacterales, Epsilonbacteraeota, Helicobacter, Oscillibacter, Verrucomicrobiales, Akkermansia, Intestinimonas, Eubacterium, Clostridiaceae, Clostridium, Bacteroides, Tyzzerella, Actinobacteria, and Bifidobacteriales. Among these bacteria, Alloprevotella showed a strong correlation with the other bacteria. CONCLUSIONS: Taken together, we concluded that mosapride may reduce intestinal bacterial translocation through regulating the gut microbiota in rats with hepatic cirrhosis.

A machine learning protocol for revealing ion transport mechanisms from dynamic NMR shifts in paramagnetic battery materials.

Solid-state nuclear magnetic resonance (ssNMR) provides local environments and dynamic fingerprints of alkali ions in paramagnetic battery materials. Linking the local ionic environments and NMR signals requires expensive first-principles computational tools that have been developed for over a decade. Nevertheless, the assignment of the dynamic NMR spectra of high-rate battery materials is still challenging because the local structures and dynamic information of alkali ions are highly correlated and difficult to acquire. Herein, we develop a novel machine learning (ML) protocol that could not only quickly sample atomic configurations but also predict chemical shifts efficiently, which enables us to calculate dynamic NMR shifts with the accuracy of density functional theory (DFT). Using structurally well-defined P2-type Na2/3(Mg1/3Mn2/3)O2 as an example, we validate the ML protocol and show the significance of dynamic effects on chemical shifts. Moreover, with the protocol, it is demonstrated that the two experimental 23Na shifts (1406 and 1493 ppm) of P2-type Na2/3(Ni1/3Mn2/3)O2 originate from two stacking sequences of transition metal (TM) layers for the first time, which correspond to space groups P63/mcm and P6322, respectively. This ML protocol could help to correlate dynamic ssNMR spectra with the local structures and fast transport of alkali ions and is expected to be applicable to a wide range of fast dynamic systems.

Modeling Electrified Pt(111)-Had/Water Interfaces from Ab Initio Molecular Dynamics.

Unraveling the atomistic structures of electric double layers (EDL) at electrified interfaces is of paramount importance for understanding the mechanisms of electrocatalytic reactions and rationally designing electrode materials with better performance. Despite numerous efforts dedicated in the past, a molecular level understanding of the EDL is still lacking. Combining the state-of-the-art ab initio molecular dynamics (AIMD) and recently developed computational standard hydrogen electrode (cSHE) method, it is possible to realistically simulate the EDL under well-defined electrochemical conditions. In this work, we report extensive AIMD calculation of the electrified Pt(111)-Had/water interfaces at the saturation coverage of adsorbed hydrogen (Had) corresponding to the typical hydrogen evolution reaction conditions. We calculate the electrode potentials of a series of EDL models with various surface charge densities using the cSHE method and further obtain the Helmholtz capacitance that agrees with experiment. Furthermore, the AIMD simulations allow for detailed structural analyses of the electrified interfaces, such as the distribution of adsorbate Had and the structures of interface water and counterions, which can in turn explain the computed dielectric property of interface water. Our calculation provides valuable molecular insight into the electrified interfaces and a solid basis for understanding a variety of electrochemical processes occurring inside the EDL.

Enhanced thallium(I) removal from wastewater using hypochlorite oxidation coupled with magnetite-based biochar adsorption.

The development of efficient and regenerable adsorbent coupled with advanced oxidation for enhanced thallium (Tl) removal has been a recent focus on wastewater treatment. In this study, a magnetite-based biochar derived from watermelon rinds was synthesized and used as a sustainable adsorbent and catalyst for hypochlorite oxidation and removal of Tl(I) from wastewater. The addition of hypochlorite substantially enhanced the Tl(I) removal under normal pH range (6-9). Maximum Tl adsorption capacity of 1123 mg/g was achieved, which is 12.3% higher than the highest value previously reported. The magnetic biochar can be regenerated using 0.1 mol/L HNO3 solution for elution in only 5 min, with a Tl desorption efficiency of 78.9%. The Tl removal efficiency was constantly higher than 98.5% during five consecutive recycle tests, indicating the effective reuse performance of the adsorbent. Oxidation, surface precipitation, pore retention and surface complexation were the main mechanisms for Tl(I) removal. The re-dissolution of Tl compounds and ion exchange of Tl cations with proton were the main mechanisms for adsorbent regeneration. Given the fast oxidation rate, high adsorption capacity, steady reusability and facile separability, this magnetic biochar-hypochlorite technique is a promising means for Tl(I) removal from wastewater. The catalytic hypochlorite oxidation induced by the magnetic biochar has also great potential to the effective removal of other pollutants.

Pentafluorosulfanyl-Substituted Benzopyran Analogues As New Cyclooxygenase-2 Inhibitors with Excellent Pharmacokinetics and Efficacy in Blocking Inflammation.

In this report, we disclose the design and synthesis of a series of pentafluorosulfanyl (SF5) benzopyran derivatives as novel COX-2 inhibitors with improved pharmacokinetic and pharmacodynamic properties. The pentafluorosulfanyl compounds showed both potency and selectivity for COX-2 and demonstrated efficacy in several murine models of inflammation and pain. More interestingly, one of the compounds, R,S-3a, revealed exceptional efficacy in the adjuvant induced arthritis (AIA) model, achieving an ED50 as low as 0.094 mg/kg. In addition, the pharmacokinetics of compound R,S-3a in rat revealed a half-life in excess of 12 h and plasma drug concentrations well above its IC90 for up to 40 h. When R,S-3a was dosed just two times a week in the AIA model, efficacy was still maintained. Overall, drug R,S-3a and other analogues are suitable candidates that merit further investigation for the treatment of inflammation and pain as well as other diseases where COX-2 and PGE2 play a role in their etiology.

Relaxation of rat thoracic aorta by fibrate drugs correlates with their potency to disturb intracellular calcium of VSMCs.

Phenotypic modifications of vascular smooth muscle cells (VSMCs) contribute to pathological changes in atherosclerosis where modulation of intracellular calcium plays an important role. In this study, three fibrate drugs, namely gemfibrozil (Gem), fenofibric acid (Fa) and bezafibrate (Beza), were revealed to relax thoracic aorta associated with their potency to reduce intracellular calcium ([Ca²âº]i) in cultured VSMCs. Relaxation effect of Gem, Fa and Beza was assayed on precontracted rat aortic rings. [Ca²âº]i level in VSMCs following addition of these fibrates was measured by laser scanning confocal microscopy or flow cytometry. Resultantly, three fibrates showed activity for vasodilation with potency order of Gem>Fa>Beza. Sustained potent reduction of [Ca²âº]i was observed with Gem 50mg/L and mild reduction with Fa 400-600mg/L, while no effect had been detected for Beza under our current system. Thus, the potency of these fibrates to relax aortic rings correlate well with their effect on [Ca²âº]i reduction, strongly implicating an underlying causal relationship. Considering that Gem potently reduces [Ca²âº]i in its clinical concentration range, this study suggests an insight to in situ pharmacological effects of anti-atherosclerosis and clinical toxicity risk.