Abstract Background Chronic obstructive pulmonary disease (COPD) represents a global health challenge, with acute exacerbations contributing to increased morbidity and mortality. Inflammation is a hallmark of COPD. This study employed machine learning techniques to assess the potential of serum levels of Clara cell secretory protein (CCSP-16), interleukin-8 (IL-8), and interleukin-6 (IL-6) for evaluating disease severity and acute exacerbations in COPD patients. Methods A cross-sectional study included 80 male COPD patients and 60 matched controls. Data collected included demographic, clinical, and spirometry results, along with serum biomarker levels measured via ELISA. Analyses combined conventional statistical methods with machine learning-based feature ranking to identify predictors of severe airway obstruction and exacerbation. Results COPD patients had significantly lower levels of CCSP-16 and IL-8 compared to healthy controls, while IL-6 levels were markedly higher in COPD patients. Using conventional statistical analyses, elevated CCSP-16 levels were significantly associated with severe airway obstruction (OR 1.87, p = 0.04) and exacerbations (OR 1.72, p = 0.01). Combining all three biomarkers improved the discrimination for severe airway obstruction (AUC = 69%, p = 0.03) and exacerbation events (AUC = 73%, p < 0.001). Feature ranking using multiple machine learning models further highlighted the integration of clinical factors with biomarker data. This approach achieved cross-validated ROC-AUC values of 0.94 and 1.0 for association with severe airway obstruction and exacerbations, respectively. Conclusions This study demonstrates the potential of CCSP-16, IL-6, and IL-8 as promising non-invasive biomarkers for COPD, as shown by both conventional statistical analyses and feature ranking using machine learning models. The integration of these biomarkers with clinical factors enhanced the predictive accuracy for severe airway obstruction and exacerbation risks. These findings highlight the critical role of combining clinical and inflammatory markers with advanced analytical techniques in improving the management of COPD.

Inflammatory bowel disease (IBD) has become a global healthcare issue, with its incidence continuing to rise, but currently there is no complete cure. Xylitol is a widely used sweetener in various foods and beverages, but there is limited research on the effects of xylitol on IBD symptoms. Study on the effect of oral xylitol in improving intestinal inflammation and damage in IBD mice, further explore the mechanism of xylitol in alleviating IBD symptoms using intestinal microbiota and non-targeted metabolomics techniques. An IBD mouse model was induced using sodium dextran sulfate (DSS). After 30 days of oral administration of xylitol, we assessed the disease activity index (DAI) scores of mice in each group. The expression levels of inflammatory factors in the colon tissues were measured using qPCR. Additionally, we examined the damage to the intestinal mucosa and tight junction structures through HE staining and immunohistochemical staining. Finally, the alterations in the gut microbiota of the mice were analyzed using 16S rDNA sequencing technology.The production of three main short-chain fatty acids (SCFAs, including acetate, propionic acid and butyric acid) in feces and the changes of serum metabolomics were measured by non-targeted metabolomics techniques. The findings indicated that xylitol effectively mitigated weight loss and improved the DAI score in mice with IBD. Moreover, xylitol reduced the expressions of Caspase-1, IL-1β, and TNF-α in the colon tissue of the mice, and increased the expressions of ZO-1 and occludin in intestinal mucosal. Xylitol could enhance the variety of intestinal bacteria in IBD mice and influenced the abundance of different bacterial species. Additionally, metabolomic analysis revealed that oral xylitol increased the levels of three main SCFAs in the feces of IBD mice, while also impacting serum metabolites. Our findings suggest that xylitol can help improve IBD symptoms. Xylitol can improve the intestinal flora of IBD mice and increase the production of SCFAs to play an anti-inflammatory role and protect the mucosal tight junction barrier. These discoveries present a fresh prophylactic treatment of IBD. Not applicable.

Introduction:Hydroxysafflor yellow A (HSYA), its primary bioactive metabolite of Carthamus tinctorius L. (safflower), has shown therapeutic potential in various inflammatory diseases. However, its role in alleviating inflammation and oxidative stress in non-alcoholic fatty liver disease (NAFLD) remains unclear. This study investigates the therapeutic effects of HSYA in mice with NAFLD, focusing on its impact on gut microbiota and serum non-targeted metabolomics to elucidate the mechanisms underlying its efficacy. Methods:NAFLD was induced in mice using a high-fat diet (HFD), followed by intragastric administration of hydroxysafflor yellow A (HSYA). Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and triglycerides (TG) were quantified to evaluate liver function and lipid metabolism. Oxidative stress markers, including superoxide dismutase (SOD) activity and malondialdehyde (MDA) concentration, were also assessed. The pro-inflammatory cytokines IL-6, TNF-α, and IL-1β in serum were measured using ELISA. The hepatic expression of NLRP3 inflammasome and its downstream effector, Caspase-1, was analyzed by Western blot. Histopathological examination of liver tissues was performed using hematoxylin and eosin (H&E) staining to evaluate structural damage. Furthermore, alterations in the gut microbiota composition were characterized via 16S rDNA sequencing of fecal samples. Untargeted metabolomics was conducted to identify serum metabolic variations and elucidate enriched metabolic pathways associated with HSYA treatment. Results:HSYA significantly inhibited HFD-induced weight gain and alleviated liver inflammation. It reduced serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and triglycerides (TG) (P < 0.05). HSYA administration decreased hepatic mRNA and protein expression of nucleotide binding oligomerization domain like receptor protein 3 (NLRP3), Caspase-1 and interleukin - 1β (IL-1β) while increasing superoxide dismutase (SOD) activity (P < 0.05). Gut microbiota analysis revealed a significant increase in the abundance of Turicibacter, while a reduction of Ruminococcus. Serum metabolomics identified a reduction in inflammation-associated metabolites, such as phenylalanine and tyrosine, alongside enhanced phenylalanine and tyrosine biosynthesis pathways. Discussion:HSYA demonstrates potent anti-inflammatory and antioxidant effects, effectively mitigating liver inflammation and oxidative stress in NAFLD mice. Its therapeutic mechanisms may involve modulating gut microbiota and regulating serum phenylalanine and tyrosine metabolism, offering insights into its potential as a treatment for NAFLD.

D-Psicose (DPS) serves as an optimal sucrose substitute, providing only 0.3% of sucrose’s energy content, while exhibiting anti-inflammatory properties and inhibiting lipid synthesis. However, its efficacy in managing non-alcoholic fatty liver disease (NAFLD) remains unclear. This study employed network pharmacology and molecular docking to identify potential DPS targets for NAFLD treatment. A high-fat diet was used to induce a NAFLD mouse model, with DPS administered in drinking water at 5% (high dose DPS group, DPSH group) and 2.5% (low dose DPS group, DPSL group) concentrations. After 12 weeks, blood lipid levels, liver lipid deposition, and inflammation were evaluated to assess the therapeutic effects of DPS. To explore its underlying mechanisms, colon contents 16S rRNA sequencing and serum untargeted metabolomics were performed. Results indicated that DPS significantly reduced lipid accumulation and inflammatory damage in the livers of NAFLD mice, improving both blood lipid profiles and oxidative stress. Network pharmacology analysis revealed that DPS primarily targets pathways associated with inflammation and oxidative stress, while molecular docking suggested its potential to inhibit the NF-κB pathway activation and the expression of the receptor for advanced glycation end-products (RAGE), findings corroborated by Western blotting. Additionally, gut microbiota and serum metabolomics analyses demonstrated that DPS improved microbiota composition by increasing the abundance of beneficial bacteria, such as Akkermansia, and restored serum metabolomic balance, enhancing anti-inflammatory and antioxidant metabolites like Tretinoin and Pyridoxamine. The non-targeted metabolomics results suggest that DPS is mediated by glutathione metabolism, arginine and proline metabolism, unsaturated fatty acid biosynthesis, and linoleic acid metabolism interferes with NAFLD progression. In conclusion, DPS may alleviate oxidative stress and lipid accumulation in NAFLD mice through the AGEs/RAGE/NF-κB pathway, while also ameliorating gut microbiota dysbiosis and serum metabolomic disturbances, fostering the production of anti-inflammatory and antioxidant metabolites.

Gut microbiota dysbiosis, a common complication in mechanically ventilated (MV) patients requiring intensive care, contributes to systemic inflammation and immune dysfunction. Probiotics have been demonstrated to modulate gut microbiota composition, improve intestinal mucosal integrity, and affect short-chain fatty acid (SCFA) production and metabolic pathways. This research examines the effects of oral probiotics on serum non-targeted metabolomics and SCFA production in these patients, with a specific focus on elucidating the mechanisms by which probiotics enhance mucosal immune function. This prospective pilot study enrolled ten mechanically ventilated patients who received add-on therapy with oral probiotics alongside routine treatment. Serum samples were collected before and after 14 days of treatment to measure procalcitonin (PCT), IL-6, IL-17, and IgA levels, while fecal samples were analyzed for the concentrations of three key SCFAs (acetic acid, propionic acid, and butyric acid). Changes in serum non-targeted metabolomics were assessed using ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). After probiotic therapy, the levels of PCT and IL-17 in the serum of patients were significantly reduced compared to before treatment, while IgA concentration significantly increased (P < 0.05), but the concentrations of the three short-chain fatty acids in the feces did not change significantly (P > 0.05). Probiotic therapy significantly affected the metabolism of arachidonic acid, glycerophospholipids, and tryptophan in patients. Oral probiotics reduce inflammation, increase IgA levels, and influence serum metabolomics. Their effects may be mediated through arachidonic acid, glycerophospholipid, and tryptophan metabolism pathways.

Diabetic liver injury is a leading cause of mortality in diabetes, with no specific treatment available. Sodium propionate (NaP) has anti-inflammatory and antioxidant properties, but its effectiveness in treating diabetic liver injury is still lacking research. The study employed network pharmacology to identify potential targets of NaP for Type 2 diabetes treatment, using oleic acid (OA) and advanced glycation end products (AGEs) to induce diabetic liver injury in HepG2 cells in vitro. Post-NaP intervention, Oil Red O staining assessed cellular lipid deposition, while Western blotting analyzed protein expression associated with oxidative stress, autophagy, and bile acid synthesis. NaP was administered to mice with diabetic liver injury induced by a high-fat and AGEs diet, and qPCR analysis was conducted to assess the expression of genes associated with inflammation, oxidative stress, and bile acid synthesis in the liver. HE staining was used to observe the liver injury, and nontargeted metabolomics analysis was used to analyze the effect of NaP on serum metabolic pathways. Network pharmacology analysis showed that NaP has anti-inflammatory and antioxidant effects, mainly involving multiple targets such as mitochondrial function, insulin resistance, and glucose metabolism. Experimental results in cells and animals demonstrated that NaP reduces lipid accumulation and inflammation in liver cells; decreases inflammatory markers like NLRP3, IL-1β, and TNF-α; enhances antioxidant factors such as serum SOD and liver Nrf2; increases the expression of the bile acid synthesis enzyme CYP7A1; and upregulates autophagy in liver cells. Serum nontargeted metabolomics indicated that NaP enhances anti-inflammatory and antioxidant metabolites, including proline and N-Acetyl-L-leucine, in diabetic liver injury mice. It potentially influences purine metabolism, amino acid synthesis (e.g., arginine, tryptophan, and tyrosine), and steroid hormone biosynthesis. This study indicates that NaP may serve as a preventive and therapeutic agent for diabetic liver injury.

Background: The primary reason for the development of chemotherapeutic intestinal mucositis induced by 5-fluorouracil (5-FU) is the activation of macrophages in the mucosa. This study aimed to explore how berberine can alleviate inflammation in macrophages and the resulting intestinal mucosal inflammation in mice induced by 5-FU.Methods: Tohoku Hospital Pediatrics-1 (THP-1) cell inflammatory response and mouse intestinal mucositis were induced by 5-FU and treated with berberine. The levels of inflammation-related factors and autophagy related proteins in THP-1 cells were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting. The concentrations of double-stranded DNA (dsDNA) and interleukin-1 beta (IL-1 beta) in mice serum and the small intestine hematoxylin-eosin (HE) staining were used to evaluate intestinal mucosal damage. Immunoglobulin A (IgA), an indicator of mucosal immunity, was detected in mice serum by enzyme-linked immunosorbent assay (ELISA). We used quantitative polymerase chain reaction (qPCR) to detect the relative contents of four important strains (Bifidobacterium, Lactobacillus, Escherichia coli, and Enterococcus) in the colon contents of mice. Additionally, we employed liquid chromatograph-mass spectrometer/mass spectrometer (LC-MS/MS) technique to measure the concentrations of three main short-chain fatty acids (acetic acid, propionic acid, and butyric acid) in the mice's plasma. Furthermore, we employed ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometer (UPLC-Q Tof-MS) technique to analyze the non-targeted metabolomics of mouse serum.Results: Berberine has been found to inhibit the expressions of NOD-Like Receptor Thermal Protein Domain Associated Protein 3 (NLRP3), Caspase-1, and IL-1 beta in THP-1 cells (p < 0.05). Additionally, it effectively suppresses the expression of autophagy related proteins LC3 and Beclin-1 in THP-1 cells (p < 0.05). Furthermore, in a mouse model study, berberine significantly enhances the levels of beneficial bacteria Bifidobacterium and Lactobacillus, as well as the concentrations of three main short-chain fatty acids (SCFAs) in the plasma of mice (p < 0.05). Moreover, it reduced the concentration of pro-inflammatory factor dsDNA and increased the mucosal immunity index IgA concentration in blood (p < 0.05). The untargeted metabolomics results demonstrated that berberine could regulate the inflammatory response of mice by impacting the metabolism of taurine, glycerol phospholipid, arachidonic acid, and primary bile acid biosynthesis.Conclusions: Berberine has demonstrated its ability to effectively suppress the inflammatory reaction of THP-1 cells induced by 5-FU. Furthermore, it also influences the "intestinal flora-metabolite-inflammation" pathway by regulating the composition of the intestinal flora, increasing the production of SCFAs, reducing the expression of inflammatory factors, and preserving the structural integrity of the intestinal mucosa.

Background: Senna leaf is a commonly used medication for treating constipation, and long-term use can cause damage to the intestinal mucosa and lead to drug dependence. But the exact mechanism remains unclear. Objective: Using non-targeted metabolomics technology to study the mechanism of senna leaf ethanol extract (EESL) inducing inflammation and oxidative stress in mice and causing side effects. Methods: EESL was administered to mice by gavage to detect inflammation and oxidative stressrelated factors in mice, and the EESL components and differential metabolites in mouse plasma were analyzed using non-targeted metabolome techniques. Results: 23 anthraquinone compounds were identified in the EESL, including sennoside and their derivatives. Administration of EESL to mice resulted in a significant increase in pro-inflammatory factors, IL-1β, and IL-6 in the plasma, while the levels of IgA significantly decreased. The levels of oxidative stress significantly increased, and the intestinal mucosal integrity was impaired. 21 endogenous in plasma metabolites were identified as differential metabolites related with taurine and taurine metabolism, glycerophospholipid metabolism, arachidonic acid metabolism, tryptophan metabolism, and sphingolipid metabolism. These metabolic pathways are related to oxidative stress and inflammation. Conclusion: Senna leaf can inhibit the expression of tight junction proteins in the intestinal mucosa and disrupt intestinal mucosal barrier integrity, exacerbating oxidative stress and inflammation induced by bacterial LPS entering the bloodstream. In addition, the impact of Senna leaf on tryptophan metabolism may be linked to the occurrence of drug dependence.

This study is aimed at assessing the impact of soluble dietary fiber inulin on the treatment of diabetes-related chronic inflammation and kidney injury in mice with type 2 diabetes (T2DM). The T2DM model was created by feeding the Institute of Cancer Research (ICR) mice a high-fat diet and intraperitoneally injecting them with streptozotocin (50 mg/kg for 5 consecutive days). The thirty-six ICR mice were divided into three dietary groups: the normal control (NC) group, the T2DM (DM) group, and the DM + inulin diet (INU) group. The INU group mice were given inulin at the dose of 500 mg/kg gavage daily until the end of the 12th week. After 12 weeks, the administration of inulin resulted in decreased serum levels of fasting blood glucose (FBG), low-density lipoprotein cholesterol (LDL-C), blood urea nitrogen (BUN), and creatinine (CRE). The administration of inulin not only ameliorated renal injury but also resulted in a reduction in the mRNA expressions of inflammatory factors in the spleen and serum oxidative stress levels, when compared to the DM group. Additionally, inulin treatment in mice with a T2DM model led to a significant increase in the concentrations of three primary short-chain fatty acids (SCFAs) (acetic acid, propionic acid, and butyric acid), while the concentration of advanced glycation end products (AGEs), a prominent inflammatory factor in diabetes, exhibited a significant decrease. The results of untargeted metabolomics indicate that inulin has the potential to alleviate inflammatory response and kidney damage in diabetic mice. This beneficial effect is attributed to its impact on various metabolic pathways, including glycerophospholipid metabolism, taurine and hypotaurine metabolism, arginine biosynthesis, and tryptophan metabolism. Consequently, oral inulin emerges as a promising treatment option for diabetes and kidney injury.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic disease in modern society. It is characterized by an accumulation of lipids in the liver and an excessive inflammatory response. Clinical trials have provided evidence that probiotics may prevent the onset and relapse of NAFLD. The aim of this study was to explore the effect of Lactiplantibacillus plantarum NKK20 strain (NKK20) on high-fat-diet-induced NAFLD in an ICR murine model and propose the underlying mechanism whereby NKK20 protects against NAFLD. The results showed that the administration of NKK20 ameliorated hepatocyte fatty degeneration, reduced total cholesterol and triglyceride concentrations, and alleviated inflammatory reactions in NAFLD mice. In addition, the 16S rRNA sequencing results indicated that NKK20 could decrease the abundance of Pseudomonas and Turicibacter and increase the abundance of Akkermansia in NAFLD mice. LC-MS/MS analysis showed that NKK20 could significantly increase the concentration of short-chain fatty acids (SCFAs) in the colon contents of mice. The obtained non-targeted metabolomics results revealed a significant difference between the metabolites in the colon contents of the NKK20 administration group and those in the high-fat diet group, in which a total of 11 different metabolites that were significantly affected by NKK20 were observed, and these metabolites were mainly involved in bile acid anabolism. UPLC-MS technical analysis revealed that NKK20 could change the concentrations of six conjugated and free bile acids in mouse liver. After being treated with NKK20, the concentrations of cholic acid, glycinocholic acid, and glycinodeoxycholic acid in livers of the NAFLD mice were significantly decreased, while the concentration of aminodeoxycholic acid was significantly increased. Thus, our findings indicate that NKK20 can regulate bile acid anabolism and promote the production of SCFA, which can inhibit inflammation and liver damage and thus prevent the development of NAFLD.

This study aims to evaluate the effect of berberine-based carbon quantum dots (Ber-CDs) on improving 5-fluorouracil (5-FU)-induced intestinal mucositis in C57BL/6 mice, and explored the mechanisms behind this effect. Thirty-two C57BL/6 mice were divided into four groups: normal control (NC), 5-FU-induced intestinal mucositis model (5-FU), 5-FU + Ber-CDs intervention (Ber-CDs), and 5-FU + native berberine intervention (Con-CDs). The Ber-CDs improved body weight loss in 5-FU-induced mice with intestinal mucositis compared to the 5-FU group. The expressions of IL-1β and NLRP3 in spleen and serum in Ber-CDs and Con-Ber groups were significantly lower than those in the 5-FU group, and the decrease was more significant in the Ber-CDs group. The expressions of IgA and IL-10 in the Ber-CDs and Con-Ber groups were higher than those in the 5-FU group, but the up-regulation was more significant in the Ber-CDs group. Compared with the 5-FU group, the relative contents of Bifidobacterium, Lactobacillus and the three main SCFAs in the colon contents were significantly increased the Ber-CDs and Con-Ber groups. Compared with the Con-Ber group, the concentrations of the three main short-chain fatty acids in the Ber-CDs group were significantly increased. The expressions of Occludin and ZO-1 in intestinal mucosa in the Ber-CDs and Con-Ber groups were higher than those in the 5-FU group, and the expressions of Occludin and ZO-1 in the Ber-CDs group were more higher than that in the Con-Ber group. In addition, compared with the 5-FU group, the damage of intestinal mucosa tissue in the Ber-CDs and Con-Ber groups were recovered. In conclusion, berberine can attenuate intestinal barrier injury and oxidative stress in mice to mitigate 5-fluorouracil-induced intestinal mucositis, moreover, the above effects of Ber-CDs were more significant than those of native berberine. These results suggest that Ber-CDs may be a highly effective substitute for natural berberine.

The activation of the monocyte-macrophage system and the damage to the renal and pancreatic tissue are common complications in patients with diabetes induced by hyper-glycemia. This study aimed to evaluate the effect and mechanism of butyrate (NaB), a metabolite of intestinal flora, on inhibiting the inflammatory response of human monocyte-macrophages (THP-1 cells) induced by high glucose and the damage of pancreatic and renal tissue in diabetic mice. The results showed that high concentration glucose significantly up-regulated the expressions of IL-1β, TNF-α, and NLRP3 in THP-1 cells and mouse spleen, and that NaB could inhibit the overexpression of those genes. The abundance of Beclin-1, LC3B and reactive oxygen species (ROS) in THP-1 cells is increased due to the high glucose concentration, and NaB can inhibit the genes responsible for upregulating the expression. In diabetic mice, vacuolar degeneration of renal tubules was observed. Then we observed that some of the epithelial cells of the renal tubules were exfoliated and some formed tubules. NaB could alleviate these pathological lesions, but NaB cannot alleviate pancreatic injury. Our results indicated that NaB could be used for the prevention and adjuvant treatment of diabetic kidney injury.

Short-chain fatty acids (SCFAs) are important anti-inflammatory metabolites of intestinal flora. Oxidized low-density lipoprotein (ox-LDL)-induced macrophage activation is critical for the formation of atherosclerosis plaque. However, the association between SCFAs and ox-LDL-induced macrophage activation with respect to the formation of atherosclerosis plaque has not yet been elucidated. The present study investigated whether SCFAs (sodium acetate, sodium propionate, and sodium butyrate) can affect ox-LDL-induced macrophage activation and potential signaling pathways via regulation of the expression of the NLRP3/Caspase-1 pathway. Using human monocyte-macrophage (THP-1) cells as a model system, it was observed that ox-LDL not only induced cell inflammatory injury but also activated the NLRP3/Caspase-1 pathway. The exogenous supplementation of three SCFAs could significantly inhibit cell inflammatory injury induced by ox-LDL. Moreover, three SCFAs decreased the expression of IL-1β and TNF-α via the inactivation of the NLRP3/Caspase-1 pathway induced by ox-LDL. Furthermore, three SCFAs affected cellular metabolism in ox-LDL-induced macrophages, as detected by untargeted metabolomics analysis. The results of the present study indicated that three SCFAs inhibited ox-LDL-induced cell inflammatory injury by blocking the NLRP3/Caspase-1 pathway, thereby improving cellular metabolism. These findings may provide novel insights into the role of SCFA intervention in the progression of atherosclerotic plaque formation.

This study evaluated the anti-inflammation effect of the three main short-chain fatty acids (SCFAs) on Acinetobacter baumannii-induced THP-1 cells. The three main SCFAs could inhibit A. baumannii-stimulated THP-1 cell NF-κB pathway activity and the expressions of NLRP3 inflamma-some and GSDMD, and increase autophagy. The three main SCFAs, especially the sodium butyrate (NaB), had the effect of down-regulation of ROS and TLR-2 expression in THP-1 cells. NaB and sodium propionate (NaPc), but not sodium acetate (NaAc), dramatically suppressed IL-1β and IFN-γ expression. The results indicated that NaB and NaPc could significantly inhibit the inflammation of THP-1 cells induced by A. baumannii, and the inhibitory effect was in the order of NaB > NaPc > NaAC. NaB and NaPc may inhibit inflammation through TLR-2/NF-κB/ROS/NLRP3 signaling pathway.

In recent years, sodium butyrate has gained increased attention for its numerous beneficial properties. However, whether sodium butyrate could alleviate inflammatory damage by macrophage activation and its underlying mechanism remains unclear. The present study used an advanced glycosylation products- (AGEs-) induced inflammatory damage model to study whether sodium butyrate could alleviate oxidative stress, inflammation, and metabolic dysfunction of human monocyte-macrophage originated THP-1 cells in a PI3K-dependent autophagy pathway. The results indicated that sodium butyrate alleviated the AGEs-induced oxidative stress, decreased the level of reactive oxygen species (ROS), increased malondialdehyde (MDA) and mRNA expression of pro-inflammatory cytokines of interleukin (IL)-1β and tumor necrosis factor (TNF)-α, and increased the content of superoxide dismutase (SOD). Sodium butyrate reduced the protein expression of the NLR family, pyrin domain-containing protein 3 (NLRP3) and Caspase-1, and decreased the nucleus expression of nuclear factor-kappaB (NF-κB). Sodium butyrate decreased the expression of light-chain-associated protein B (LC3B) and Beclin-1, and inhibited autophagy. Moreover, sodium butyrate inhibited the activation of the PI3K/Akt pathway in AGEs-induced THP-1 cells. In addition, the metabolomics analysis showed that sodium butyrate could affect the production of phosphatidylcholine, L-glutamic acid, UDP-N-acetylmuraminate, biotinyl-5'-AMP, and other metabolites. In summary, these results revealed that sodium butyrate inhibited autophagy and NLRP3 inflammasome activation by blocking the PI3K/Akt/NF-κB pathway, thereby alleviating oxidative stress, inflammation, and metabolic disorder induced by AGEs.

Dysbiosis is a crucial manifestation of dyslipidemia; however, oral supplementation of probiotic modulates the intestinal commensal composition. The protective mechanism of probiotics against hyperlipidemia is still under investigation. To elucidate the hypolipidemic effect of Lactobacillus rhamnosus TR08 through the analysis of gut microbiota and lipid metabolomics, we investigated changes in gut microbiota and lipid metabolomic phenotypes in mice by real time quantitative PCR and untargeted metabolomics analysis. High fat diet–induced dyslipidemia mice were orally administered with TR08 for 8 weeks. The proinflammatory cytokines (interleukin–2 and interferon–γ) levels in spleen and aortic wall injury in the mice fed with a high-fat diet were inhibited after treatment with TR08 at 1 × 108 CFU per day per mouse. TR08 also reshaped the gut microbiota with increases of the relative abundances of Bifidobacterium and Bacteroides, reduced the abundance of the pro–pathogen bacterial Enterococcus, increased the serum level of short chain fatty acids (SCFAs) contents, and promoted sphingomholipid metabolic pathway. The results indicated that TR08 could improve the intestinal microbiota of mice to increase the production of SCFAs, and then play the anti–inflammation induced by hyperlipidemia and reduce the inflammatory injury of blood vessel wall. Therefore, TR08 can potentially be used as a hypolipidemic effect probiotic in further interventions.

5-Fluorouracil (5-FU) is a used chemotherapy drug for cancer, and its main side effect is intestinal mucositis which causes chemotherapy to fail. It was known that short-chain fatty acids (SCFAs) can inhibit immune cell release of various proinflammatory factors and inhibit excessive intestinal inflammation. However, the inhibitory effect of SCFAs on 5-FU-induced intestinal mucositis is still unclear. To simulate the effects of SCFAs on immune and intestinal epithelial cells, the cells (THP-1 cells and Caco-2 cells) were pretreated with sodium acetate (NaAc), sodium propionate (NaPc) and sodium butyrate (NaB), then inflammation was induced by 5-FU. The expressions of reactive oxygen species (ROS), Beclin-1, LC3-II, NF-κB p65, NLRP3 inflammasome, proinflammatory/anti-inflammatory cytokines and mucosal tight junction proteins were determined. In our results, the three SCFAs could inhibit ROS expressions, NLRP3, Caspase-1, IL-1β, IL-6, IL-18, Beclin-1 and LC3-II, when induced by 5-FU. In a 5-FU-induced chemoentermuctis mouse model, Lactobacillus rhamnoides can increase the concentrations of three SCFAs in faeces and increase the concentrations of IL-1β, IL-6 and IgA in serum, and decrease the expressions of NLRP3 and IL-17 in spleen cells. The expressions of ZO-1 and Occludin in intestinal mucosa were significantly increased. These results indicated that the three SCFAs can effectively suppress the inflammation of THP-1 cells and Caco-2 cells and maintain tight junction integrity in intestinal mucosal epithelial cells.

目的 分析肺炎克雷伯菌肝脓肿(KPLA)患者的临床特征,了解肺炎克雷伯菌毒力基因携带情况,为临床早期诊断和合理治疗提供参考.方法 回顾性分析江苏大学附属医院2017年7月—2019年8月收治的34例脓液培养阳性的细菌性肝脓肿患者的临床资料,分为KPLA组和非肺炎克雷伯菌肝脓肿(NKPLA)组.采用VITEK 2 Compact全自动微生物鉴定及药敏分析仪进行细菌鉴定及药敏试验,采用黏液丝试验确定肺炎克雷伯菌的高黏液表型,采用PCR法进行耐药基因、荚膜血清分型及毒力基因检测,并对结果进行统计学分析.结果 34例细菌性肝脓肿中有22例为KPLA.KPLA组患者多有基础疾病糖尿病,而NKPLA组患者则多有基础疾病胆道疾病或恶性肿瘤.22株肺炎克雷伯菌中仅2株(9.1％)同时对环丙沙星、左旋氧氟沙星和复方磺胺甲口恶唑耐药.22株肺炎克雷伯菌中共检出2种ESBLs耐药基因,分别是blaTEM(36.4％)、blaCTX-M-1(27.3％).本研究中22株肺炎克雷伯菌均为高毒力肺炎克雷伯菌,检出高毒力荚膜血清型5种,以K1型为主,占68.2％.22株肺炎克雷伯菌均携带毒力基因rmpA、iucA、iroB、iutA.结论 KPLA好发于中老年男性,多有糖尿病基础疾病,其菌株均为高毒力肺炎克雷伯菌,以K1血清型为主,并携带了大量的毒力基因,对临床常用的抗菌药物耐药率较低,但可携带耐药基因,需引起临床医生的高度关注.

肠道微生物种群是人体最大的共生生态系统,在维持肠道生态平衡中发挥着重要作用.肠道微生态失衡的本质是共生微生物和致病微生物之间的失衡.大量研究表明,肠道内的各种共生微生物是保障肠黏膜免疫系统成熟所不可或缺的,而致病微生物的存在会引起各种免疫功能紊乱,最终导致疾病发生.另一方面,肠道菌群中细菌的种类和丰度也受到肠黏膜免疫系统的监视和影响,炎症状态下肠道微生态的平衡将被打破,导致多种肠道疾病发生.综述了近年来肠道菌群与肠黏膜免疫系统之间相互作用的研究进展.

The overactivation of macrophages causes chronic inflammatory diseases. Short-chain fatty acids (SCFAs), potential drugs for clinical treatment, are modulators of macrophage inflammatory reaction. Therefore, the modulation of macrophage-mediated cell activity is expected to become a new therapeutic strategy for inflammatory diseases caused by Mycoplasma pneumoniae. In this study, 2 kinds of SCFAs (propionate and butyrate) were found to have anti-inflammatory effects in M. pneumoniae-stimulated THP-1 cells inflammatory. They inhibited the expressions of IL-4, IL-6, ROS, and NLRP3 inflammasome, while enhancing the expressions of IL-10 and IFN-γ. Our study revealed these 2 agents to repress transcriptional activities of NF-κB, which are important modulators of inflammation. Meanwhile, SCFAs can significantly enhance the autophagy induced by M. pneumoniae. Considering that SCFAs have few side effects, they might be the promising adjuvant therapy for the prevention and/or treatment of various inflammatory diseases.