Inflammation and nutrition are interrelated, and both are related to depression. This study explored the association between the C-reactive protein (CRP)-albumin-lymphocyte (CALLY) index, a novel immunonutrition scoring system, and depression in patients with type 2 diabetes mellitus (T2DM).

We included 3517 patients with T2DM from the National Health and Nutrition Examination Survey 2005-2010 and 2015-2018. The Patient Health Questionnaire-9 was used to evaluate depression. The CALLY index was based on a comprehensive assessment of serum CRP, serum albumin, and the lymphocyte counts from whole blood. Weighted multivariate logistic regression models were used to examine the relationship between the CALLY index and depression. The restricted cubic spline was applied to explore the nonlinear relationship.

Compared with the non-depressed group, CALLY index and albumin in the depressed group were significantly reduced, while CRP and lymphocytes were significantly increased (P < 0.05). After adjusting for covariates, only the CALLY index significantly decreased (the highest quartile vs the lowest quartile, odds ratio = 0.58, 95 % confidence interval: 0.38-0.89, P = 0.014). The non-linear association between the CALLY index and depression was not significant (P for nonlinear=0.69). The results of subgroup analysis were basically consistent (P for interaction > 0.05).

The CALLY index was significantly negatively correlated with depression in American patients with diabetes and served as a potential marker for early identification.

The intricate interplay between natural compounds like curcumin and the gut microbiome has gained significant attention in recent years due to their potential therapeutic implications in various health conditions. Curcumin, a polyphenolic compound derived from turmeric, exhibits diverse pharmacological properties, including anti-inflammatory, antioxidant, and anticancer effects. Understanding how curcumin modulates gut microbiota composition and function is crucial for elucidating its therapeutic mechanisms. This review examines the current literature on the interactions between curcumin and the gut microbiome. A systematic search of relevant databases was conducted to identify studies investigating the effects of curcumin on gut microbial diversity and abundance. Key findings from studies exploring curcumin's efficacy in neurological disorders, gastrointestinal diseases, and metabolic dysfunction are synthesized and discussed. Studies have demonstrated that curcumin supplementation can modulate gut microbiota composition and function, leading to beneficial effects on gut health and homeostasis. Mechanisms underlying curcumin's therapeutic effects include immune modulation, neuroprotection, and inflammation regulation. However, challenges such as poor bioavailability and safety concerns remain significant hurdles to overcome. The interactions between curcumin and the gut microbiome hold promise for therapeutic interventions in a diverse range of health conditions. Further research is needed to optimize curcumin formulations, improve bioavailability, and address safety concerns.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by motor symptoms and non-motor symptoms. It has been found that intestinal issues usually precede motor symptoms. Microorganisms in the gastrointestinal tract can affect central nervous system through the microbiota-gut-brain axis. Accumulating evidence has shown that disturbances in the microbiota-gut-brain axis are linked with PD. Thus, this pathway appears to be a promising therapeutic target for treatment of PD.

In this review, we mainly described gut dysbiosis in PD and their underlying mechanisms for mediating neuroinflammation and peripheral immune response in PD pathology and futher discussed the potential small-molecule compounds and genic therapeutic strategies targeting the microbiota-gut-brain axis and their applications in PD.

Studies have found that some small molecule compounds and alterations of inflammation-related genes can improve the motor and non-motor symptoms of PD by improving the microbiota-gut-brain axis, which may provide potentially beneficial drugs and molecular targets for the therapies of PD.

Type 2 diabetes mellitus (T2DM), a serious metabolic disorder, is a worldwide health problem due to the alarming rise in prevalence and elevated morbidity and mortality. Chronic hyperglycemia, insulin resistance, and ineffective insulin effect and secretion are hallmarks of T2DM, leading to many serious secondary complications. These include, in particular, cardiovascular disorders, diabetic neuropathy, nephropathy and retinopathy, diabetic foot, osteoporosis, liver damage, susceptibility to infections and some cancers. Polyphenols such as flavonoids, phenolic acids, stilbenes, tannins, and lignans constitute an extensive and heterogeneous group of phytochemicals in fresh fruits, vegetables and their products. Various in vitro studies, animal model studies and available clinical trials revealed that flavonoids (e.g., quercetin, kaempferol, rutin, epicatechin, genistein, daidzein, anthocyanins), phenolic acids (e.g., chlorogenic, caffeic, ellagic, gallic acids, curcumin), stilbenes (e.g., resveratrol), tannins (e.g., procyanidin B2, seaweed phlorotannins), lignans (e.g., pinoresinol) have the ability to lower hyperglycemia, enhance insulin sensitivity and improve insulin secretion, scavenge reactive oxygen species, reduce chronic inflammation, modulate gut microbiota, and alleviate secondary complications of T2DM. The interaction between polyphenols and conventional antidiabetic drugs offers a promising strategy in the management and treatment of T2DM, especially in advanced disease stages. Synergistic effects of polyphenols with antidiabetic drugs have been documented, but also antagonistic interactions that may impair drug efficacy. Therefore, additional research is required to clarify mutual interactions in order to use the knowledge in clinical applications. Nevertheless, dietary polyphenols can be successfully applied as part of supportive treatment for T2DM, as they reduce both obvious clinical symptoms and secondary complications.

This study aimed to investigate the impact of electroacupuncture (EA) on blood glucose levels, gut microbiota, short-chain fatty acids (SCFAs), and glucagon-like peptide-1 (GLP-1) in a rat model of type 2 diabetes mellitus (T2DM).

Forty Sprague-Dawley (SD) rats were randomly assigned to five groups (n = 8/group) using a random number table: normal control, T2DM model, electroacupuncture (EA), EA + antibiotics (EA + A), and antibiotics (A). The normal rats received a standard diet and saline gavage, while the other groups were fed a high-fat diet and emulsion. The EA + A and A groups received additional antibiotic solution gavage. The normal, model, and A groups were immobilized and restrained for 30 min, six times per week, for 4 weeks. The EA and EA + A groups received EA treatment at specific acupoints for 30 min, six times per week, for 4 weeks. EA parameters were continuous waves at 10 Hz and 1-2 mA. During the intervention, water and food consumption, body weight, fasting blood glucose (FBG), and oral glucose tolerance test (OGTT) were monitored. Pancreatic tissue was examined using hematoxylin and eosin (H&E) staining. Fecal microbial communities were analyzed by 16S rDNA sequencing, and short-chain fatty acids (SCFAs) were measured using gas chromatography-mass spectrometry (GC-MS). Serum levels of fasting insulin (FINS), glycated hemoglobin (HbA1c), and glucagon-like peptide-1 (GLP-1) were determined using enzyme-linked immunosorbent assay (ELISA).

EA significantly improved daily water intake, food consumption, and body weight in T2DM rats (p < 0.01). EA also reduced FBG, the area under the curve of the OGTT, FINS, and homeostasis model assessment of insulin resistance (HOMA-IR) in T2DM rats (p < 0.05). The ELISA results showed a lower concentration of HbA1c in the EA group (p < 0.05). EA improved the overall morphology and area of pancreatic islets, increased the number of β-cell nuclei, and alleviated β-cell hypertrophy. The abundance of operational taxonomic units (OTUs) in the EA group increased than the model group (p < 0.05), and EA upregulated the Shannon, Chao1, and Ace indices (p < 0.05). EA increased the concentrations of acetic acid, butyric acid, and GLP-1 (p < 0.05). Correlation analysis revealed negative associations between Lactobacillaceae (R = -0.81, p = 0.015) and Lactobacillus (R = -0.759, p = 0.029) with FBG. Peptostreptococcaceae and Romboutsia were negatively correlated with HbA1c (R = -0.81, p = 0.015), while Enterobacteriaceae was positively correlated with OGTT (R = 0.762, p = 0.028). GLP-1 was positively correlated with acetic acid (R = 0.487, p = 0.001), butyric acid (R = 0.586, p = 0.000), isovaleric acid (R = 0.374, p = 0.017), valeric acid (R = 0.535, p = 0.000), and caproic acid (R = 0.371, p = 0.018). Antibiotics disrupted the intestinal microbiota structure and weakened the therapeutic effects of EA.

EA effectively improved glucose metabolism in T2DM rats. The hypoglycemic effects of EA were associated with the regulation of gut microbiota, SCFAs, and GLP-1.

This study aims to systematically evaluate the safety and efficacy of curcumin as an adjunctive treatment for patients with ulcerative colitis (UC) and to assess the methodological quality of the published studies.

A comprehensive search was conducted in PubMed, Embase, and CENTRAL databases for randomized controlled trials published up to August 18, 2023. Two independent reviewers screened studies based on predefined criteria. Meta-analysis was performed using a random-effects model with RevMan 5.4. Heterogeneity was assessed using Cochran's Q test and I² statistic.

Eight randomized controlled trials involving 482 patients were included. Seven studies reported clinical remission, and three reported endoscopic remission. Compared to the placebo group, adjunctive curcumin therapy significantly improved clinical remission (RR=2.33, 95 % CI: 1.25 to 4.34; P = 0.008; I²=80 %). Although endoscopic remission showed an increasing trend, it was not statistically significant (RR=4.17, 95 % CI: 0.63 to 27.71; P = 0.14; I²=80 %). Significant improvements were also observed in clinical improvement (RR=1.93, 95 % CI: 1.10 to 3.36; P = 0.02; I²=56 %) and endoscopic improvement (RR=1.76, 95 % CI: 1.12 to 2.77; P = 0.01; I²=62 %) in the curcumin group. No serious adverse events were reported. Subgroup analysis indicated a positive correlation between treatment efficacy and dosage, with no significant impact of administration method or follow-up duration on the pooled results or heterogeneity.

Curcumin as an adjunctive treatment shows promise in improving clinical and endoscopic outcomes in UC patients without significant adverse effects. However, due to the limited number of studies and substantial heterogeneity, further large-scale randomized controlled trials are necessary to confirm these findings.

Diabetes mellitus is a common chronic metabolic disease characterized by a high incidence and disability rate. Intestinal flora refers to the microbial community that lives in the intestines and plays a crucial role in maintaining intestinal health and the human immune system. In recent years, an increasing body of research has revealed a close relationship between intestinal flora and diabetes. The pathophysiological mechanisms between them have also been constantly uncovered, and the regulation of intestinal flora has shown promising efficacy in the adjuvant treatment of diabetes. This study mainly summarized the characteristics and mechanisms of intestinal flora in patients with diabetes in recent years, as well as the methods of regulating intestinal flora to prevent and treat diabetes, and prospected the future research direction. This will offer a theoretical basis for the clinical adjuvant treatment of diabetes with intestinal flora and the development of new drugs.

Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder closely associated with chronic inflammation. Curcumin, a polyphenolic lipophilic compound, has been shown to improve the intestinal mucosal barrier and reduce low-grade systemic inflammation. This study aimed to assess the effects of curcumin on attenuation of PCOS in a mouse model and to explore the underlying mechanisms involved. C57BL/6J mice were divided into 4 groups (n = 15 per group): CON: control group, CON/CUR: CON with curcumin group, MOD: model group, MOD/CUR: MOD with curcumin group. The MOD and MOD/CUR groups were injected with dehydroepiandrosterone (DHEA) (6 mg/100 g BW) dissolved in soybean oil to induce a PCOS-like state. After curcumin intervention (200 mg/kg) for 45 days, the mice were euthanized for analysis of various physiological and biochemical parameters. In MOD/CUR group, significant decreases in body weight (BW) (p = 0.0254), testosterone (T) levels (p = 0.0052), luteinizing hormone (LH) levels (p = 0.0438), and the LH/follicle-stimulating hormone (FSH) (p = 0.0271) levels were observed, while estradiol (E2) (p = 0.0415) level and insulin sensitivity (p = 0.0441) were increased. Histological examination (HE) staining of ovarian and colon tissues showed that curcumin ameliorated both PCOS-associated morphological changes and colon tissue pathology. Western blot and immunohistochemistry analyses of colon tissues revealed increased levels of tight junction proteins, ZO-1 (Western blot, p = 0.0360; immunohistochemistry, p = 0.0273) and occluding (Western blot, p = 0.0189; immunohistochemistry, p = 0.0224) in the MOD/CUR group. Additionally, inflammatory indicators from plasma and ovary, including IL-17 A (plasma, p = 0.0120; ovary, p = 0.0414), IL-6 (plasma, p = 0.0344; ovary, p = 0.0379), TNF-α (plasma, p = 0.0078; ovary, p = 0.0488), and lipopolysaccharides (LPS) (plasma, p = 0.0144), were decreased, while IL-10 (plasma, p = 0.0270; ovary, p = 0.0267) was increased in MOD/CUR group. The levels of NF-κB p65 (p = 0.0229), TLR-4 (p = 0.0462) and MyD88 (p = 0.0152) in ovarian tissues were significantly increased in MOD/CUR group. Our results revealed that curcumin alleviates PCOS by inhibiting TLR4/MyD88/NF-κB signaling pathway activation and reducing intestinal mucosal permeability. These findings suggest that curcumin may provide a potential clinical approach for managing PCOS.

The gut-brain-metabolic axis has emerged as a critical area of research, highlighting the intricate connections between the gut microbiome, metabolic processes, and cognitive function. This review article delves into the complex interplay between these interconnected systems, exploring their role in the development of insulin resistance and cognitive decline. The article emphasizes the pivotal influence of the gut microbiota on central nervous system (CNS) function, demonstrating how microbial colonization can program the hypothalamic-pituitary-adrenal (HPA) axis for stress response in mice. It further elucidates the mechanisms by which gut microbial carbohydrate metabolism contributes to insulin resistance, a key factor in the pathogenesis of metabolic disorders and cognitive impairment. Notably, the review highlights the therapeutic potential of targeting the gut-brain-metabolic axis through various interventions, such as dietary modifications, probiotics, prebiotics, and fecal microbiota transplantation (FMT). These approaches have shown promising results in improving insulin sensitivity and cognitive function in both animal models and human studies. The article also emphasizes the need for further research to elucidate the specific microbial species and metabolites involved in modulating the gut-brain axis, as well as the long-term effects and safety of these therapeutic interventions. Advances in metagenomics, metabolomics, and bioinformatics are expected to provide deeper insights into the complex interactions within the gut microbiota and their impact on host health. Overall, this comprehensive review underscores the significance of the gut-brain-metabolic axis in the pathogenesis and treatment of metabolic and cognitive disorders, offering a promising avenue for the development of novel therapeutic strategies targeting this intricate system.

The gut microbiome plays a critical role in maintaining gut and metabolic health, and its composition is often altered by aging and obesity. This study aimed to investigate the protective effects of curcumin on gut dysbiosis, gut barrier integrity, and bile acid homeostasis in aged mice fed a high-fat, high-sugar diet (HFHSD). Eighteen- to twenty-one-month-old male C57BL/6 mice were divided into groups fed a normal chow diet or HFHSD, with or without curcumin supplementation (0.4% w/w) for 8 and 15 weeks. We assessed body weight, food intake, insulin sensitivity, gut microbiota composition, and gene expression in the gut and liver and performed histological analysis of gut tissues. Curcumin supplementation prevented HFHSD-induced weight gain and metabolic disturbances. In the gut, curcumin-treated mice showed a higher abundance of beneficial bacterial genera, such as Lachnospiraceae, Akkermansia, Mucispirillum, and Verrucomicrobiota, alongside a lower abundance of harmful bacterial genera like Desulfobacteria, Alistipes, and Muribaculaceae compared to control. This shift in gut microbiota was associated with improved gut integrity, as demonstrated by increased expression of the tight junction protein occludin and reduced levels of the pro-inflammatory marker interleukin-1β in the ileum. Additionally, curcumin modulated hepatic gene expression involved in bile acid homeostasis, suggesting a positive effect on liver health. Curcumin supplementation can alleviate the negative effects of aging and an HFHSD on the gut microbiome, improve gut barrier integrity, and maintain bile acid homeostasis. These findings highlight curcumin's potential as a dietary intervention for managing obesity- and age-associated gut health issues.

Intestinal barrier is a first line of defense that prevents entry of various harmful substances from the lumen into the systemic environment. Impaired barrier function with consequent translocation of harmful substances into systemic circulation ("leaky gut") is a central theme in many gastrointestinal, autoimmune, mental, and metabolic diseases. Probiotics have emerged as a promising strategy to maintain intestinal integrity and address "leaky gut". Using in silico, in vitro and avian in vivo analyses, we previously showed that two novel L. reuteri strains, PTA-126787 (L. reuteri 3630) and PTA-126788 (L. reuteri 3632), isolated from broiler chickens possess favorable safety profiles. Consistent with a recent study, here we show that L. reuteri 3630 and 3632 are phylogenetically similar to human L. reuteri strains. Daily administration of high doses of L. reuteri 3630 and 3632 to Sprague Dawley rats for 28 days was found to be safe with no adverse effects. More importantly, administration of L. reuteri 3630 and 3632 significantly reduced markers associated with alcohol-induced leaky gut, by downregulating inflammatory cytokines and upregulating anti-inflammatory cytokines in an alcohol model of leaky gut in mice. While L. reuteri 3630 cells and supernatant showed no activation, L. reuteri 3632 cells but not supernatant showed activation of AhR, a key transcription factor that regulates gut and immune homeostasis. L. reuteri 3630 is creamish white in morphology typical of Lactobacillus species and L. reuteri 3632 displays a unique orange pigmentation, which was stable even after passaging for 480 generations. We identified a rare polyketide biosynthetic gene cluster in L. reuteri 3632 that likely encodes for the orange-pigmented secondary metabolite. Similar to L. reuteri 3632 cells, the purified orange metabolite activated AhR. All together, these data provide evidence on the phylogenetic relatedness, safety, efficacy, and one of the likely mechanisms of action of L. reuteri 3630 and 3632 for potential probiotic applications to address "leaky gut" and associated pathologies in humans.

The human gut microbiota plays a crucial role in maintaining metabolic health, with substantial evidence linking its composition to insulin resistance. This study aims to analyze the global scholarly contributions on the relationship between intestinal microbiota and insulin resistance from 2000 to 2024.

A bibliometric analysis was conducted using data from Scopus and Web of Science Core Collection. The search strategy included terms related to "Gastrointestinal Microbiome" and "Insulin Resistance" in the title or abstract.

The analysis of 1,884 relevant studies from 510 sources was conducted, revealing a mean citation of 51.36 per manuscript and a remarkable annual growth rate of 22.08%. The findings highlight the significant role of gut microbiota in insulin resistance, corroborating prior studies that emphasize its influence on metabolic disorders. The literature review of the current study showed key mechanisms include the regulation of short-chain fatty acids (SCFAs) and gut hormones, which are critical for glucose metabolism and inflammation regulation. The analysis also identifies "Food and Function" as the most productive journal and Nieuwdorp M. as a leading author, underscoring the collaborative nature of this research area.

The consistent increase in publications in the field of gut microbiota and insulin resistance indicates growing recognition of the gut microbiota's therapeutic potential in treating insulin resistance and related metabolic disorders. Future research should focus on standardizing methodologies and conducting large-scale clinical trials to fully realize these therapeutic possibilities.

Gut barrier is not only part of the digestive organ but also an important immunological organ for the hosts. The disruption of gut barrier can lead to various diseases such as obesity and colitis. In recent years, traditional Chinese medicine (TCM) has gained much attention for its rich clinical experiences enriched in thousands of years. After orally taken, TCM can interplay with gut microbiota. On one hand, TCM can modulate the composition and function of gut microbiota. On the other hand, gut microbiota can transform TCM compounds. The gut microbiota metabolites produced during the actions of these interplays exert noticeable pharmacological effects on the host especially gut barrier. Recently, a large number of studies have investigated the repairing and fortifying effects of TCM on gut barriers from the perspective of gut microbiota and its metabolites. However, no review has summarized the mechanism behand this beneficiary effects of TCM. In this review, we first briefly introduce the unique structure and specific function of gut barrier. Then, we summarize the interactions and relationship amidst gut microbiota, gut microbiota metabolites and TCM. Further, we summarize the regulative effects and mechanisms of TCM on gut barrier including physical barrier, chemical barrier, immunological barrier, and microbial barrier. At last, we discuss the effects of TCM on diseases that are associated gut barrier destruction such as ulcerative colitis and type 2 diabetes. Our review can provide insights into TCM, gut barrier and gut microbiota.

Insulin resistance (IR) is considered the pathogenic driver of diabetes, and can lead to obesity, hypertension, coronary artery disease, metabolic syndrome, and other metabolic disorders. Accumulating evidence indicates that the connection between gut microbiota and IR. This bibliometric analysis aimed to summarize the knowledge structure of gut microbiota in IR.

Articles and reviews related to gut microbiota in IR from 2013 to 2022 were retrieved from the Web of Science Core Collection (WoSCC), and the bibliometric analysis and visualization were performed by Microsoft Excel, Origin, R package (bibliometrix), Citespace, and VOSviewer.

A total of 4 749 publications from WoSCC were retrieved, including 3 050 articles and 1 699 reviews. The majority of publications were from China and USA. The University Copenhagen and Shanghai Jiao Tong University were the most active institutions. The journal of Nutrients published the most papers, while Nature was the top 1 co-cited journal, and the major area of these publications was molecular, biology, and immunology. Nieuwdorp M published the highest number of papers, and Cani PD had the highest co-citations. Keyword analysis showed that the most frequently occurring keywords were "gut microbiota", "insulin-resistance", "obesity", and "inflammation". Trend topics and thematic maps showed that serum metabolome and natural products, such as resveratrol, flavonoids were the research hotspots in this field.

This bibliometric analysis summarised the hotspots, frontiers, pathogenesis, and treatment strategies, providing a clear and comprehensive profile of gut microbiota in IR.

The online version contains supplementary material available at 10.1007/s40200-023-01342-x.

Intestinal microbiota have been demonstrated to be involved in the development of NAFLD, while the relationship between the severity of NAFLD and intestinal microbiota is still not fully elucidated. Sheng-Jiang Powder (SJP) showed exact efficacy in treating SFL and great potential in regulating intestinal microbiota, but the effects need to be further addressed in NASH and liver fibrosis.

To investigate the differences in intestinal microbiota of NAFLD with different severity and the effect of SJP on liver damage and intestinal microbiota.

NAFLD mice models with different severity were induced by high-fat diet (HFD) or choline-deficient, L-amino acid-defined high-fat diet (CDAHFD) feeding and then treated with SJP/normal saline.

Biochemical blood tests, H&E/Masson/Oil Red O/IHC staining, Western blot, and 16SrDNA sequencing were performed to explore intestinal microbiota alteration in different NAFLD models and the effect of SJP on liver damage and intestinal microbiota.

Intestinal microbiota alteration was detected in all NAFLD mice. SJP induced increased expression of Pparγ and alleviated liver lipid deposition in all NAFLD mice. Microbiome analysis revealed obvious changes in intestinal microbiota composition, while SJP significantly elevated the relative abundance of Roseburia and Akkermansia, which were demonstrated to be beneficial for improving inflammation and intestinal barrier function.

Our results demonstrated that SJP was effective in improving lipid metabolism in NAFLD mice, especially in mice with SFL. The potential mechanism may be associated with the regulation of intestinal microbiota.

Intestinal dysfunction and microbiome changes are actively discussed in the modern literature as the most important link in the development of neurodegenerative changes in Parkinson's disease. The article discusses the pathogenetic chain «microbiome- intestine-brain», as well as factors that affect the development of intestinal dysbiosis. A promising direction for influencing microflora and inflammatory changes in the intestine is the use of polyphenols, primarily curcumin. The review of experimental, laboratory, clinical research proving the pleiotropic effect of curcumin, including its antioxidant, anti-inflammatory, neuroprotective effects, realized both through peripheral and central mechanisms is presented.

Constipation-predominant irritable bowel syndrome (IBS-C) is a functional bowel disease that affects 10-20% of the population worldwide. Curcumin (CUR) is widely used in traditional Chinese medicine to treat IBS, but its mechanism of action needs further investigation.

In this study, we used mosapride (MOS) as a positive control to evaluate the changes in gut microbiota in IBS-C rat models after treatment with CUR or MOS by analyzing 16S rDNA variation. In addition, we used enzyme immunoassay kits and immunohistochemical analysis to investigate whether CUR or MOS influenced serotonin (5-HT), substance P (SP), and vasoactive intestinal peptide (VIP) levels in the serum and colon of IBS-C rats.

The study showed that rats supplemented with CUR showed significantly increased fecal weight, fecal water content, small intestine transit rate and significantly decreased serum levels of 5-HT, VIP and SP compared to the IBS group (p < 0.05). In addition, treatment with CUR changed the relative abundance of Blautia, Sutterella, Acetanaerobacterium and Ruminococcus2 in the gut microbiota.

This study showed that the efficacy of CUR on IBS-C was possibly by modulating the microbiota and lowering the serum levels of HT, SP, and VIP.

Fructus mori polysaccharide (FMP) has a variety of biological activities. In this study, the results showed that FMP alleviated hyperglycemia, insulin resistance, hyperlipidemia, endotoxemia, and high metabolic inflammation levels in type 2 diabetic (T2DM) mice. Next, it was found that the above beneficial effects of FMP on diabetic mice were significantly attenuated after antibiotics eliminated intestinal microbiota (IM) of mice. In addition, FMP suppressed intestinal inflammation and oxidative stress levels by inhibiting the activation of the TLR4/MyD88/NF-κB pathway, and indirectly upregulated the expression of the tight junction proteins Claudin-1, Occludin, and Zonula occlusionn-1 (ZO-1) to repair the intestinal barrier. Interestingly, the protective effect of FMP on the intestinal barrier was also attributed to its regulation of IM. The 16S rRNA and Spearman correlation analysis showed that FMP could repair the intestinal barrier to improve T2DM by remodeling specific IM, especially by significantly inhibiting 93.66 % of endotoxin-producing Shigella and promoting the proliferation of probiotic Allobaculum and Bifidobacterium by 16.31 % and 19.07 %, respectively. This study provided a theoretical support for the application of FMP as a novel probiotic in functional foods for diabetes.

There are no effective targeted therapies to treat acute respiratory distress syndrome (ARDS). Recently, the commonly used diabetes and obesity medications, glucagon-like peptide-1 (GLP-1) receptor agonists, have been found to have anti-inflammatory properties. We, therefore, hypothesized that liraglutide pretreatment would attenuate murine sepsis-induced acute lung injury (ALI). We used a two-hit model of ALI (sepsis+hyperoxia). Sepsis was induced by intraperitoneal injection of cecal slurry (CS; 2.4 mg/g) or 5% dextrose (control) followed by hyperoxia [HO; fraction of inspired oxygen ([Formula: see text]) = 0.95] or room air (control; [Formula: see text] = 0.21). Mice were pretreated twice daily with subcutaneous injections of liraglutide (0.1 mg/kg) or saline for 3 days before initiation of CS+HO. At 24-h post CS+HO, physiological dysfunction was measured by weight loss, severity of illness score, and survival. Animals were euthanized, and bronchoalveolar lavage (BAL) fluid, lung, and spleen tissues were collected. Bacterial burden was assessed in the lung and spleen. Lung inflammation was assessed by BAL inflammatory cell numbers, cytokine concentrations, lung tissue myeloperoxidase activity, and cytokine expression. Disruption of the alveolar-capillary barrier was measured by lung wet-to-dry weight ratios, BAL protein, and epithelial injury markers (receptor for advanced glycation end products and sulfated glycosaminoglycans). Histological evidence of lung injury was quantified using a five-point score with four parameters: inflammation, edema, septal thickening, and red blood cells (RBCs) in the alveolar space. Compared with saline treatment, liraglutide improved sepsis-induced physiological dysfunction and reduced lung inflammation, alveolar-capillary barrier disruption, and lung injury. GLP-1 receptor activation may hold promise as a novel treatment strategy for sepsis-induced ARDS. Additional studies are needed to better elucidate its mechanism of action.NEW & NOTEWORTHY In this study, pretreatment with liraglutide, a commonly used diabetes medication and glucagon-like peptide-1 (GLP-1) receptor agonist, attenuated sepsis-induced acute lung injury in a two-hit mouse model (sepsis + hyperoxia). Septic mice who received the drug were less sick, lived longer, and displayed reduced lung inflammation, edema, and injury. These therapeutic effects were not dependent on weight loss. GLP-1 receptor activation may hold promise as a new treatment strategy for sepsis-induced acute respiratory distress syndrome.

Diabetes is a significant chronic endocrine/metabolism disorder that can result in a number of life-threatening consequences. According to research, the gut microbiota is strongly linked to the development of diabetes, making it a viable target for diabetes treatment. The intestinal microbiota affects intestinal barrier function, organism immunity, and thus glucose metabolism and lipid metabolism. According to research, a disruption in the intestinal microbiota causes a decrease in short-chain fatty acids (SCFAs), alters the metabolism of bile acids (BAs), branched-chain amino acids (BCAAs), lipopolysaccharide (LPS), and endotoxin secretion, resulting in insulin resistance, chronic inflammation, and the progression to type 2 diabetes mellitus (T2DM). Astragali Radix is a medicinal herb of the same genus as food that has been extensively researched for treating diabetes mellitus with promising results in recent years. Polysaccharides, saponins, flavonoids, and other components are important. Among them, Astragaloside has a role in protecting the cellular integrity of the pancreas and liver, can leading to alleviation of insulin resistance and reducing blood glucose and triglyceride (TC) levels; The primary impact of Astragalus polysaccharides (APS) on diabetes is a decrease in insulin resistance, encouragement of islet cell proliferation, and suppression of islet β cell death; Astragali Radix flavonoids are known to enhance immunity, anti-inflammatory, regulate glucose metabolism and control the progression of diabetes. This study summarizes recent studies on Astragali Radix and its group formulations in the treatment of type 2 diabetes mellitus by modulating the intestinal microbiota.

Singapore grouper iridovirus (SGIV) is a new ranavirus species in the Iridoviridae family, whose high lethality and rapid spread have resulted in enormous economic losses for the aquaculture industry. Curcumin, a polyphenolic compound, has been proven to possess multiple biological activities, including antibacterial, antioxidant, and antiviral properties. This study was conducted to determine whether curcumin protected orange-spotted grouper (Epinephelus coioides) from SGIV-induced intestinal damage by affecting the inflammatory response, cell apoptosis, oxidative stress, and intestinal microbiota. Random distribution of healthy orange-spotted groupers (8.0 ± 1.0 cm and 9.0 ± 1.0 g) into six experimental groups (each group with 90 groupers): Control, DMSO, curcumin, SGIV, DMSO + SGIV, and curcumin + SGIV. The fish administered gavage received DMSO dilution solution or 640 mg/L curcumin every day for 15 days and then were injected intraperitoneally with SGIV 24 h after the last gavage. When more than half of the groupers in the SGIV group perished, samples from each group were collected for intestinal health evaluation. Our results showed that curcumin significantly alleviated intestine damage and repaired intestinal barrier dysfunction, which was identified by decreased intestine permeability and serum diamine oxidase (DAO) activity and increased expressions of tight junction proteins during SGIV infection. Moreover, curcumin treatment suppressed intestinal cells apoptosis and inflammatory response caused by SGIV and protected intestinal cells from oxidative injury by enhancing the activity of antioxidant enzymes, which was related to the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. Moreover, we found that curcumin treatment restored the disruption of the intestinal microbiota caused by SGIV infection. Our study provided a theoretical basis for the functional development of curcumin in aquaculture by highlighting the protective effect of curcumin against SGIV-induced intestinal injury.

Diabetic cognitive dysfunction (DCD) is one of the most insidious complications of type 2 diabetes mellitus, which can seriously affect the ability to self-monitoring of blood glucose and the quality of life in the elderly. Previous pathological studies of cognitive dysfunction have focused on neuronal dysfunction, characterized by extracellular beta-amyloid deposition and intracellular tau hyperphosphorylation. In recent years, astrocytes have been recognized as a potential therapeutic target for cognitive dysfunction and important participants in the central control of metabolism. The disorder of gut microbiota and their metabolites have been linked to a series of metabolic diseases such as diabetes mellitus. The imbalance of intestinal flora has the effect of promoting the occurrence and deterioration of several diabetes-related complications. Gut microbes and their metabolites can drive astrocyte activation.

We reviewed the pathological progress of DCD related to the "gut microbiota-astrocyte" axis in terms of peripheral and central inflammation, intestinal and blood-brain barrier (BBB) dysfunction, systemic and brain energy metabolism disorders to deepen the pathological research progress of DCD and explore the potential therapeutic targets.

"Gut microbiota-astrocyte" axis, unique bidirectional crosstalk in the brain-gut axis, mediates the intermediate pathological process of neurocognitive dysfunction secondary to metabolic disorders in diabetes mellitus.

The past couple of decades in particular have seen a rapid increase in the prevalence of type 2 diabetes mellitus (T2DM), a debilitating metabolic disorder characterised by insulin resistance. The insufficient efficacy of current management strategies for insulin resistance calls for additional therapeutic options. The preponderance of evidence suggests potential beneficial effects of curcumin on insulin resistance, while modern science provides a scientific basis for its potential applications against the disease. Curcumin combats insulin resistance by increasing the levels of circulating irisin and adiponectin, activating PPARγ, suppressing Notch1 signalling, and regulating SREBP target genes, among others. In this review, we bring together the diverse areas pertaining to our current understanding of the potential benefits of curcumin on insulin resistance, associated mechanistic insights, and new therapeutic possibilities. Teaser: Current approaches to manage insulin resistance are not highly efficacious, which necessitates additional therapeutic options; curcumin combats insulin resistance by improving the levels of circulating irisin and adiponectin, upregulating and activating PPARγ, and suppressing Notch‑1 signalling.

Polyphenols, which are naturally occurring bioactive compounds in fruits and vegetables, are emerging as potential therapeutics for neurological disorders such as Parkinson's disease (PD). Polyphenols have diverse biological activities, such as anti-oxidative, anti-inflammatory, anti-apoptotic, and α-synuclein aggregation inhibitory effects, which could ameliorate PD pathogenesis. Studies have shown that polyphenols are capable of regulating the gut microbiota (GM) and its metabolites; in turn, polyphenols are extensively metabolized by the GM, resulting in the generation of bioactive secondary metabolites. These metabolites may regulate various physiological processes, including inflammatory responses, energy metabolism, intercellular communication, and host immunity. With increasing recognition of the importance of the microbiota-gut-brain axis (MGBA) in PD etiology, polyphenols have attracted growing attention as MGBA regulators. In order to address the potential therapeutic role of polyphenolic compounds in PD, we focused on MGBA. DATA AVAILABILITY: Data will be made available on request.

Impaired intestinal barrier and immune dysfunction promote the development of type 2 diabetes (T2D). Group 3 innate lymphoid cells (ILC3s), which are enriched in the intestinal lamina propria, are key for intestinal barrier integrity. However, there is a paucity of data on circulating ILC3s in patients with T2D.

To examine the characteristics of ILC3s in patients with T2D and identify the relationship between ILC3s and clinical indicators of T2D.

Fifty-nine patients with T2D and thirty controls were enrolled in this retrospective study. Peripheral blood mononuclear cells were isolated and analyzed by flow cytometry and plasma cytokine levels were measured by enzyme-linked immunosorbent assays.

The proportion of circulating ILC3s in the T2D group was significantly lower than that in controls and showed a negative correlation with fasting glucose and glycated hemoglobin and a positive correlation with granulocyte-macrophage colony-stimulating factor (GM-CSF). Similarly, the proportion of circulating integrin α4⁺ ILC3s was also significantly lower in the T2D group and showed a negative correlation with fasting glucose and glycated hemoglobin and a positive correlation with GM-CSF. Moreover, the level of circulating integrin α4⁺ ILC3s showed a positive correlation with the proportion of circulating dendritic cells (DCs), which was also decreased in patients with T2D and positively associated with GM-CSF.

ILC3s, especially integrin α4⁺ ILC3s, were decreased in patients with T2D and showed a negative correlation with disease severity. These cell subsets may delay the progression of T2D by promoting DC differentiation via the secretion of GM-CSF.

Impaired gut barrier contributes to the progression of type 2 diabetes mellitus (T2DM), and the gut microbiota and metabolome play an important role in it. Hemicellulose, a potential prebiotics, how its supplementation impacted the glucose level, the impaired gut barrier, and the gut microbiota and metabolome in T2DM remained unclear.

In this study, some mice were arranged randomly into four groups: db/db mice fed by a compositionally defined diet (CDD), db/db mice fed by a CDD with 10% and 20% hemicellulose supplementation, and control mice fed by a CDD. Body weight and fasting blood glucose levels were monitored weekly. The gut barrier was evaluated. Fresh stool samples were analyzed using metagenomic sequencing and liquid chromatography-mass spectrometry to detect gut microbiota and metabolome changes. Systemic and colonic inflammation were evaluated.

Better glycemic control, restoration of the impaired gut barrier, and lowered systemic inflammation levels were observed in db/db mice with the supplementation of 10 or 20% hemicellulose. The gut microbiota showed significant differences in beta diversity among the four groups. Fifteen genera with differential relative abundances and 59 significantly different metabolites were found. In the db/db group, hemicellulose eliminated the redundant Faecalibaculum and Enterorhabdus. The increased succinate and ursodeoxycholic acid (UDCA) after hemicellulose treatment were negatively correlated with Bifidobacterium, Erysipelatoclostridium, and Faecalibaculum. In addition, hemicellulose reduced the colonic expressions of TLR2/4 and TNF-α in db/db mice.

Hemicellulose may serve as a potential therapeutic intervention for T2DM by improving impaired intestinal mucosal barrier integrity, modulating gut microbiota composition, and altering the metabolic profile.

Fabry disease is a lysosomal storage disease caused by mutations in the GLA gene that encodes alpha-galactosidase (AGAL). The disease causes abnormal globotriaosylceramide (Gb3) storage in the lysosomes. Variants responsible for the genotypic spectrum of Fabry disease include mutations that abolish enzymatic activity and those that cause protein instability. The latter can be successfully treated with small molecules that either bind and stabilize AGAL or indirectly improve its cellular activity. This paper describes the first attempt to reposition curcumin, a nutraceutical, to treat Fabry disease. We tested the efficacy of curcumin in a cell model and found an improvement in AGAL activity for 80% of the tested mutant genotypes (four out of five tested). The fold-increase was dependent on the mutant and ranged from 1.4 to 2.2. We produced evidence that supports a co-chaperone role for curcumin when administered with AGAL pharmacological chaperones (1-deoxygalactonojirimycin and galactose). The combined treatment with curcumin and either pharmacological chaperone was beneficial for four out of five tested mutants and showed fold-increases ranging from 1.1 to 2.3 for DGJ and from 1.1 to 2.8 for galactose. Finally, we tested a long-term treatment on one mutant (L300F) and detected an improvement in Gb3 clearance and lysosomal markers (LAMP-1 and GAA). Altogether, our findings confirmed the necessity of personalized therapies for Fabry patients and paved the way to further studies and trials of treatments for Fabry disease.

Intestinal absorption of food is one of the sources of glucose. Insulin resistance and impaired glucose tolerance caused by lifestyle and diet are the precursors of type 2 diabetes. Patients with type 2 diabetes have trouble controlling their blood sugar levels. For long-term health, strict glycemic management is necessary. Although it is thought to be well correlated with metabolic diseases like obesity, insulin resistance, and diabetes, its molecular mechanism is still not completely understood. Disturbed microbiota triggers the gut immune response to reshape the gut homeostasis. This interaction not only maintains the dynamic changes of intestinal flora, but also preserves the integrity of the intestinal barrier. Meanwhile, the microbiota establishes a systemic multiorgan dialog on the gut-brain and gut-liver axes, intestinal absorption of a high-fat diet affects the host's feeding preference and systemic metabolism. Intervention in the gut microbiota can combat the decreased glucose tolerance and insulin sensitivity linked to metabolic diseases both centrally and peripherally. Moreover, the pharmacokinetics of oral hypoglycemic medications are also influenced by gut microbiota. The accumulation of drugs in the gut microbiota not only affects the drug efficacy, but also changes the composition and function of them, thus may help to explain individual therapeutic variances in pharmacological efficacy. Regulating gut microbiota through healthy dietary patterns or supplementing pro/prebiotics can provide guidance for lifestyle interventions in people with poor glycemic control. Traditional Chinese medicine can also be used as complementary medicine to effectively regulate intestinal homeostasis. Intestinal microbiota is becoming a new target against metabolic diseases, so more evidence is needed to elucidate the intricate microbiota-immune-host relationship, and explore the therapeutic potential of targeting intestinal microbiota.

Metabolic syndrome mainly includes obesity, type 2 diabetes (T2DM), alcoholic fatty liver (NAFLD) and cardiovascular diseases. According to the ancient experience philosophy of Yin-Yang, monarch-minister compatibility of traditional Chinese medicine, prescription is given to treat diseases, which has the advantages of small toxic and side effects and quick effect. However, due to the diversity of traditional Chinese medicine ingredients and doubts about the treatment theory of traditional Chinese medicine, the mechanism of traditional Chinese medicine is still in doubt. Gastrointestinal tract is an important part of human environment, and participates in the occurrence and development of diseases. In recent years, more and more TCM researches have made intestinal microbiome a new frontier for understanding and treating diseases. Clinically, nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus (DM) often co-occur. Our aim is to explain the mechanism of interaction between gastrointestinal microbiome and traditional Chinese medicine (TCM) or traditional Chinese medicine formula to treat DM and NAFLD. Traditional Chinese medicine may treat these two diseases by influencing the composition of intestinal microorganisms, regulating the metabolism of intestinal microorganisms and transforming Chinese medicinal compounds.

To explore the effect of curcumin on the proliferation of renal cell carcinoma and analyze its regulation mechanism.

In RCC cell lines of A498 and 786-O, the effects of curcumin (2.5, 5, 10 µ mo/L) on the proliferation were analyzed by Annexin V+PI staining. Besides, A498 was inoculated into nude mice to establish tumorigenic models, and the model mice were treated with different concentrations of curcumin (100, 200, and 400 mg/kg), once daily for 30 days. Then the tumor diameter was measured, the tumor cells were observed by hematoxylin-eosin staining, and the protein expressions of miR-148 and ADAMTS18 were detected by immunohistochemistry. In vitro, after transfection of miR-148 mimics, miR-148 inhibitor or si-ADAMTS18 in cell lines, the expression of ADAMTS18 was examined by Western blotting and the cell survival rate was analyzed using MTT. Subsequently, Western blot analysis was again used to examine the autophagy phenomenon by measuring the relative expression level of LC3-II/LC3-I; autophagy-associated genes, including those of Beclin-1 and ATG5, were also examined when miR-148 was silenced in both cell lines with curcumin treatment.

Curcumin could inhibit the proliferation of RCC in cell lines and nude mice. The expression of miR-148 and ADAMTS18 was upregulated after curcumin treatment both in vitro and in vivo (P<0.05). The cell survival rate was dramatically declined upon miR-148 or ADAMTS18 upregulated. However, si-ADAMTS18 treatment or miR-148 inhibitor reversed these results, that is, both of them promoted the cell survival rate.

Curcumin can inhibit the proliferation of renal cell carcinoma by regulating the miR-148/ ADAMTS18 axis through the suppression of autophagy in vitro and in vivo. There may exist a positive feedback loop between miR-148 and ADAMTS18 gene in RCC.

Xieriga-4 decoction (XRG-4) is a classic prescription Mongolian medicine that has potent diuretic and anti-inflammatory activities. However, its functional components remain unknown.

This study aimed to identify the chemical components in XRG-4 and its metabolome in vivo.

An ultra-performance liquid chromatography coupled with a quadrupole time-of-flight tandem mass spectrometry based approach was proposed to systematically profile the chemicolome and metabolome of XRG-4.

A total of 106 constituents were identified in XRG-4. Eighty-nine components were identified in biological samples, including 78 in urine (24 prototypes and 54 metabolites), 26 in feces (19 prototypes and 7 metabolites), and 9 in plasma (5 prototypes and 4 metabolites). In other tissues, only a few compounds, including alkaloids and iridoids, were detected.

This comprehensive investigation of the chemical and metabolic profiles of XRG-4 provides a scientific foundation for its quality control and administration of clinically-safe medication.

Parkinson's disease (PD) is a common neurodegenerative disorder, accompanied by motor deficits as well as gastrointestinal dysfunctions. Recent studies have proved that the disturbance of gut microbiota and metabolism contributes to the pathogenesis of PD; however, the mechanisms underlying these effects have yet to be elucidated. Curcumin (CUR) has been reported to provide neuroprotective effects on neurological disorders and modulate the gut flora in intestinal-related diseases. Therefore, it is of significant interest to investigate whether CUR could exert a protective effect on PD and whether the effect of CUR is dependent on the intestinal flora and subsequent changes in metabolites.

In this study, we investigated the neuroprotective effects of CUR on a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). 16S rRNA sequencing was performed to explore the profile of the gut microbiota among controls, MPTP-treated mice and CUR-treated mice. Then, antibiotic treatment (ABX) and fecal microbiota transplantation (FMT) experiments were conducted to examine the role of intestinal microbes on the protective effects of CUR in PD mice. Furthermore, ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS)-based metabolomics analysis was used to identify the landscape of the CUR-driven serum metabolome. Finally, Pearson's analysis was conducted to investigate correlations between the gut flora-metabolite axis and CUR-driven neuroprotection in PD.

Our results showed that CUR intervention effectively improved motor deficits, glial cell activation, and the aggregation of α-synuclein (α-syn) in MPTP-treated mice. 16S rRNA sequencing showed elevated abundances of Muribaculaceae, Lactobacillaceae, Lachnospiraceae and Eggerthellaceae but depleted abundances of Aerococcaceae and Staphylococcaceae in CUR-treated mice when compared with MPTP mice. ABX and FMT experiments further confirmed that the gut microbiota was required for CUR-induced protection in PD mice. Serum metabolomics analysis showed that CUR notably upregulated the levels of tyrosine, methionine, sarcosine and creatine. Importantly, strong correlations were identified among crucial taxa (Aerococcaceae, Staphylococcaceae, Muribaculaceae, Lactobacillaceae, Lachnospiraceae and Eggerthellaceae), pivotal metabolites (tyrosine, methionine, sarcosine and creatine) and the motor function and pathological results of mice. CUR treatment led to a rapid increase in the brain levels of tyrosine and levodopa (dopa) these changes were related to the abundances of Lactobacillaceae and Aerococcaceae.

CUR exerts a protective effect on the progression of PD by modulating the gut microbiota-metabolite axis. Lactobacillaceae and Aerococcaceae, along with key metabolites such as tyrosine and dopa play a dominant role in CUR-associated neuroprotection in PD mice. Our findings offer unique insights into the pathogenesis and potential treatment of PD.

Diabetes mellitus comprises a group of heterogeneous disorders, which are usually subdivided into type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Both genetic and environmental factors have been implicated in the onset of diabetes. Type 1 diabetes primarily involves autoimmune insulin deficiency. In comparison, type 2 diabetes is contributed by the pathological state of insulin deficiency and insulin resistance. In recent years, significant differences were found in the abundance of microflora, intestinal barrier, and intestinal metabolites in diabetic subjects when compared to normal subjects. To further understand the relationship between diabetes mellitus and intestinal flora, this paper summarizes the interaction mechanism between diabetes mellitus and intestinal flora. Furthermore, the natural compounds found to treat diabetes through intestinal flora were classified and summarized. This review is expected to provide a valuable resource for the development of new diabetic drugs and the applications of natural compounds.

Traditional Chinese herbal medicine often exerts the therapeutic effect of "treating different diseases with the same method" in clinical practice; in other words, it is a kind of herbal medicine that can often treat two or even multiple diseases; however, the biological mechanism underlying its multi-path and multi-target pharmacological effects remains unclear. Growing evidence has demonstrated that gut microbiota dysbiosis plays a vital role in the occurrence and development of several diseases, and that the root cause of herbal medicine plays a therapeutic role in different diseases, a phenomenon potentially related to the improvement of the gut microbiota. We used local intestinal diseases, such as ulcerative colitis, and systemic diseases, such as type 2 diabetes, as examples; comprehensively searched databases, such as PubMed, Web of Science, and China National Knowledge Infrastructure; and summarized the related studies. The results indicate that multiple individual Chinese herbal medicines, such as Rhizoma coptidis (Huang Lian), Curcuma longa L (Jiang Huang), and Radix Scutellariae (Huang Qin), and Chinese medicinal compounds, such as Gegen Qinlian Decoction, Banxia Xiexin Decoction, and Shenling Baizhu Powder, potentially treat these two diseases by enriching the diversity of the gut microbiota, increasing beneficial bacteria and butyrate-producing bacteria, reducing pathogenic bacteria, improving the intestinal mucosal barrier, and inhibiting intestinal and systemic inflammation. In conclusion, this study found that a variety of traditional Chinese herbal medicines can simultaneously treat ulcerative colitis and type 2 diabetes, and the gut microbiota may be a significant target for herbal medicine as it exerts its therapeutic effect of "treating different diseases with the same method".

Diabetes mellitus is a serious metabolic disorder that can lead to a number of life-threatening complications. Studies have shown that intestinal microbiota is closely related to the development of diabetes, making it a potential target for the treatment of diabetes. In recent years, research on the active ingredients of traditional Chinese medicine (TCM), TCM compounds, and prepared Chinese medicines to regulate intestinal microbiota and improve the symptoms of diabetes mellitus is very extensive. We focus on the research progress of TCM active ingredients, herbal compounds, and prepared Chinese medicines in the treatment of diabetes mellitus in this paper. When diabetes occurs, changes in the abundance and function of the intestinal microbiota disrupt the intestinal environment by disrupting the intestinal barrier and fermentation. TCM and its components can increase the abundance of beneficial bacteria while decreasing the abundance of harmful bacteria, regulate the concentration of microbial metabolites, improve insulin sensitivity, regulate lipid metabolism and blood glucose, and reduce inflammation. TCM can be converted into active substances with pharmacological effects by intestinal microbiota, and these active substances can reverse intestinal microecological disorders and improve diabetes symptoms. This can be used as a reference for diabetes prevention and treatment.

The study objective was to investigate the effects of electroacupuncture performed at the he-sea and front-mu acupoints on the intestinal microflora and intestinal barrier in db/db mice and to explore the related mechanism in type 2 diabetes mellitus.

Db/m mice in the normal control group (NOC), electroacupuncture group (EA), metformin group (MET) and T2DM group (T2DM) were used as model controls, and db/db mice were used in all three groups, with 8 mice in each group. The treatment period was 2 weeks. Fasting blood glucose (FBG) and triglyceride (TG) levels were measured. Lipopolysaccharide (LPS) and tumor necrosis factor-α (TNF-α) levels were detected by enzyme-linked immune sorbent assay (ELISA). The ileal tissue was stained with hematoxylin-eosin staining (H&E), and histopathological changes were observed under a light microscope. Illumina sequencing was used to analyze the V4 region of the 16S rRNA gene to evaluate the effect of EA on the intestinal flora.

Our results suggest that EA treatment can reduce the expression of diabetes-related markers, with an effect similar to that of metformin. After EA intervention, the abundance of Firmicutes and the ratio of Firmicutes to Bacteroidetes increased, while the abundances of Bacteroidetes and Eubacterium decreased. In addition, the serum levels of LPS and TNF-α in the electroacupuncture group were downregulated, and ileal tissue damage was alleviated under an electron microscope.

EA combined with acupoints can restore the intestinal flora structure, decrease the blood LPS level, reduce levels of inflammation, maintain the integrity of the intestinal barrier, and play a therapeutic role in the treatment of T2DM, mainly by increasing the abundance of Firmicutes and the ratio of Firmicutes to Bacteroidetes and decreasing the abundances of Bacteroidetes and Eubacterium.

Type 2 diabetes mellitus (T2DM), one of the fastest growing metabolic diseases, has been characterized by metabolic disorders including hyperglycemia, hyperlipidemia and insulin resistance (IR). In recent years, T2DM has become the fastest growing metabolic disease in the world. Studies have indicated that patients with T2DM are often associated with intestinal flora disorders and dysfunction involving multiple organs. Metabolites of the intestinal flora, such as bile acids (BAs), short-chain fatty acids (SCFAs) and amino acids (AAs)may influence to some extent the decreased insulin sensitivity associated with T2DM dysfunction and regulate metabolic as well as immune homeostasis. In this paper, we review the changes in the gut flora in T2DM and the mechanisms by which the gut microbiota modulates metabolites affecting T2DM, which may provide a basis for the early identification of T2DM-susceptible individuals and guide targeted interventions. Finally, we also highlight gut microecological therapeutic strategies focused on shaping the gut flora to inform the improvement of T2DM progression.