As one of the three major malignant tumors in women, the morbidity of endometrial cancer is second only to that of cervical cancer and is increasing yearly. Its etiological mechanism is not clear, and the risk factors are numerous and common and are closely related to obesity, hypertension, diabetes, etc. The gut microbiota has many strains, which play a considerable part in normal digestion and absorption in the human body and the regulation of the immune response. In the last few years, research on the gut microbiota has been unprecedentedly popular, and it has been confirmed that the gut microbiota closely correlates with the occurrence and development of all kinds of benign and malignant diseases. In this article, the effects of the gut microbiota and its metabolites on the occurrence and development of endometrial cancer is reviewed, and its application in the prevention, diagnosis and treatment of endometrial cancer is explored.

This study aimed to investigate causal relationships between gut microbiota, blood metabolites, immune cell traits, circulating inflammatory proteins, and myopia through Mendelian randomization (MR) analysis.

Mendelian randomization study.

Genome-wide association study (GWAS) data of 412 gut microbiota, 1400 blood metabolites/metabolite ratios, 731 immune cell traits, and 91 circulating inflammatory proteins from the public GWAS database. Genome-wide association study data of myopia from the public GWAS database and FinnGen consortium.

Two-sample MR analysis and meta-analysis were employed using 4 methods, with inverse-variance weighted as the primary approach, to investigate potential causal links. Metabolic pathway analysis was conducted to explore metabolic pathways. The Cochran Q-test, MR-Egger intercept test, and MR-PRESSO were used for sensitivity analyses. Mediation and reverse MR analyses were also carried out to identify potential mediation relationships and modification effects of myopia.

Causal relationships between gut microbiota, blood metabolites, immune cell traits, circulating inflammatory proteins, and myopia.

We identified causal effects of 34 and 22 gut microbiota/bacterial pathways, 131 and 98 blood metabolites/metabolite ratios, 60 and 37 immune cell traits, and 5 and 2 circulating inflammatory proteins on myopia (ukb-b-6353 and R10_H7_MYOPIA, respectively). Overlapping causal relationships were found for 1 gut bacterial pathway, 10 blood metabolites/metabolite ratios, and 2 immune cell traits across both outcomes; however, none of these overlaps reached significance after meta-analysis. The Small Molecule Pathway Database and Kyoto Encyclopedia of Genes and Genomes database enriched 14 significant pathways. Flavin adenine dinucleotide was involved in 8 pathways in both databases. Furthermore, the causal effect of glycochenodeoxycholate glucuronide on myopia was mediated by acetyl-CoA fermentation to butanoate lI, with mediation proportion of 19.03% (ukb-b-6353) and 19.48% (R10_H7_MYOPIA). Reverse MR analysis identified modification effects of myopia (ukb-b-6353) on gut microbiota, blood metabolites, and circulating inflammatory proteins.

These findings demonstrated significant causal relationships between gut microbiota, blood metabolites, immune cell traits, circulating inflammatory proteins, and myopia. Gut microbiota pathway may mediate the causal effects of blood metabolite on myopia. This may provide researchers with a new perspective in exploring the biological mechanisms of myopia and may lead to the exploration of earlier treatment strategies.

The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Type 2 diabetes mellitus (T2DM) is a global health challenge with limited efficacy of current treatments, necessitating alternative therapies. Plant-derived pectin, composed of galacturonic acid and structural domains such as homogalacturonan, has shown promise as an anti-diabetic agent. Pectin exerts its therapeutic effects through multiple mechanisms, including enhancing β-cell function, regulating glucose metabolism, improving insulin sensitivity, inhibiting digestive enzymes, and restoring gut microbiota balance. Its bioactivity is influenced by physicochemical properties like molecular weight, degree of methylation, and structural complexity. This review explores the anti-diabetic potential of pectin, its structure-activity relationships, and mechanisms of action, providing insights for its development as a novel therapeutic agent in T2DM management.

Helicobacter pylori (H. pylori) infection has the capacity to alter the gut microbiota composition. There is a significant correlation between H. pylori infection and type 2 diabetes mellitus (T2DM). Further research is necessary to explore whether gut microbiota plays a role in the relationship between H. pylori and T2DM.

Fecal samples were obtained from 44 patients with T2DM, including 20 who tested positive for H. pylori and 24 who tested negative. Intestinal microbiota composition was analyzed via 16S rRNA V3-V4 amplicon sequencing. Differences in microbial distribution and significant microbial biomarkers were identified between H. pylori positive and negative groups. A Spearman correlation analysis assessed the relationship between intestinal microbiota and glycemic parameters. Additionally, PICRUSt2 was used to predict intestinal bacterial functions.

Results indicate that in H. pylori (+) T2DM patients, HbA1c levels were significantly higher (8.9% vs. 8.1%, p = 0.021), while both the C-peptide peak (3.70 vs. 5.98 ng/mL, p = 0.040) and fasting C-peptide levels (1.42 vs. 2.31 ng/mL, p = 0.008) were significantly lower compared to H. pylori (-) T2DM groups. A total of 11 colonic phyla and 100 genera were identified in all fecal samples. In groups positive for H. pylori, there was a significant enrichment of the phylum Proteobacteria, while the genera Lactobacillus, Butyricimonas, and Akkermansia were significantly reduced (all p < 0.05). Correlation analysis showed that the abundance of the genera Butyricimonas (p = 0.01) and Akkermansia (p = 0.048) were negatively correlated with fasting plasma glucose. KEGG pathway analysis indicated a significant enrichment of methylmalonyl-CoA mutase and succinyl-CoA in H. pylori-infected T2DM patients.

This study suggests that T2DM patients with H. pylori infection exhibit more impaired pancreatic islet function potentially due to H. pylori-induced alterations in the gut microbiota.

Research has established links between the gut microbiome (GM) and both obesity and type 2 diabetes (T2D), which is much discussed, but underexplored. This study employed body mass index (BMI) as the measurement of obesity to delve deeper into the correlations from a genetic perspective.

We performed the Mendelian randomization (MR) analysis to examine the causal effects of GM on T2D and BMI, and vice versa. Genome-wide association study (GWAS) summary datasets were utilized for the analysis, including T2D (N = 933,970), BMI (N = 806,834), and two GM datasets from the international consortium MiBioGen (211 taxa, N = 18,340) and the Dutch Microbiome Project (DMP) (207 taxa, N = 7,738). These datasets mainly cover European populations, with additional cohorts from Asia and other regions. To further explore the potential mediating role of GM in the connections between BMI and T2D, their interaction patterns were summarized into a network.

MR analysis identified 9 taxa that showed protective properties against T2D. Seven species were within the Firmicutes and Bacteroidales phyla in the DMP, and two were from the MiBioGen (Odds Ratio (OR): 0.94-0.95). Conversely, genetic components contributing to the abundance of 12 taxa were associated with increased risks of T2D (OR: 1.04-1.12). Furthermore, T2D may elevate the abundance of seven taxa (OR: 1.03-1.08) and reduce the abundance of six taxa (OR: 0.93-0.97). In the analysis of the influence of the genetic component of BMI on GM composition, BMI affected 52 bacterial taxa, with 28 decreasing (OR: 0.75-0.92) and 24 increasing (OR: 1.08-1.27). Besides, abundances of 25 taxa were negatively correlated with BMI (OR: 0.95-0.99), while positive correlations were detected for 14 taxa (OR: 1.01-1.05). Notably, we uncovered 11 taxa genetically associated with both BMI and T2D, which formed an interactive network.

Our findings provide evidence for the GM-mediated links between obesity and T2D. The identification of relevant GM taxa offers valuable insights into the potential role of the microbiome in these diseases.

Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, has emerged as a potential contributor to diabetic retinopathy (DR) progression. However, its molecular mechanisms in DR remain unclear. This study integrates network toxicology and multi-omics analyses to elucidate TMAO's role in DR pathogenesis. We identified TMAO-related targets through integration of CTD, SuperPred, and GeneCards databases. Differential expression analysis of DR-related genes was performed using GSE60436 and GSE102485 datasets. We intersected these with TMAO targets to identify key genes. Functional enrichment and pathway analyses were conducted, followed by immune cell infiltration assessment using ssGSEA. Machine learning algorithms (LASSO and RF) identified key marker genes, validated through GSE94019 dataset and in vitro experiments. Molecular docking explored interactions between TMAO and key proteins. We identified 45 TMAO-related targets implicated in DR. Functional analysis revealed enrichment in stress response and inflammatory pathways. Differential pathway analysis indicated significant upregulation of immune and apoptotic pathways in DR. Immune cell infiltration analysis showed increased levels of cytotoxic and inflammatory cells in DR. CASP3, CXCR4, and MAPK1 emerged as key marker genes, their expression significantly upregulated in PDR patients. Molecular docking highlighted stable interactions between TMAO and these proteins, suggesting potential modulation of their activity. TMAO-associated targets are enriched in inflammatory, oxidative, and apoptotic pathways in PDR tissues, suggesting a potential (but not causal) link to DR pathology. Our findings highlight the gut-retina axis in DR and provide a framework for targeting TMAO-mediated mechanisms in diabetic complications.

Background/Objectives: Timbe (Acaciella angustissima) is a legume recognized for its environmental benefits, such as soil restoration, wildlife nutrition, and the presence of biologically active compounds. This study investigates the antioxidant, pharmacological, and antimicrobial properties of Timbe. Methods: The total phenolic content, flavonoids, and condensed tannins from Timbe flowers, seeds, and pods were quantified, and their antioxidant activity was evaluated using the DPPH and ABTS assays. Enzymatic activities were assessed through α-amylase, α-glucosidase, and ACE-I inhibition, and antimicrobial properties were tested against various bacterial strains. Results: The pods and flowers exhibited higher antioxidant capacities compared to seeds, effectively neutralizing free radicals. Flavonoids and condensed tannins showed positive correlations with antioxidant activity and the inhibition of α-amylase and α-glucosidase, suggesting the potential benefits of these metabolites in blood glucose control. Timbe also demonstrated ACE-I inhibition, particularly the flowers. Regarding antimicrobial activity, the pods displayed moderate inhibition against E. coli, K. pneumoniae, and S. aureus. Conclusions: The results indicate that different parts of Timbe (flowers, seeds, and pods) possess significant therapeutic potential for preventing and treating metabolic disorders and bacterial infections.

We aimed to determine if oral faecal microbiota transplantation improves indices of glycaemic control, changes the faecal dysbiosis indices, alters faecal short-chain fatty acid and bile acid profiles and increases serum glucagon-like-peptide 1 concentrations in diabetic dogs.

In this prospective randomised, placebo-controlled, double-blinded pilot study, we recruited nine diabetic dogs (five faecal microbiota transplantation and four placebo) and nine healthy controls.

Compared to healthy dogs, diabetic dogs had altered faecal short-chain fatty acid and bile acid profiles. In the first 30 days, the faecal microbiota transplantation group had a more rapid decline in interstitial glucose; however, the mean interstitial glucose of the faecal microbiota transplantation recipients did not differ from the placebo recipients at the end of the study. Compared with placebo, faecal microbiota transplantation recipients had a decreased 24-hour water intake at day 60 and increased faecal abundance of Faecalibacterium.

This study provides a proof of concept for faecal microbiota transplantation in canine diabetes, and its data could inform the design of future large-scale studies. Further investigation is required to determine whether faecal microbiota transplantation would have any role as an adjunctive therapy in canine diabetes and to elucidate the mechanisms by which faecal microbiota transplantation may provide a beneficial clinical effect in canine diabetes.

This study explores the anti-atherosclerosis (AS) effects of Buyang Huanwu Decoction (BYHWD), focusing on its regulatory effects on the TLR4/NF-κB/NLRP3 inflammatory pathway, gut microbiota metabolites, and mitochondrial autophagy. Through the triple regulatory mechanisms of gut microbiota, the TLR4/NF-κB/NLRP3 inflammatory pathway, and mitochondrial autophagy, this study explores a novel strategy for stabilizing vulnerable AS plaques.

The active components of Buyang Huanwu Decoction (BYHWD) were detected using LC-MS/MS. By feeding a high-fat diet (HFD) and adding 1.3 % choline chloride to the drinking water to induce ApoE-/- mice gut microbiota dysbiosis, an AS mouse model with vulnerable plaques was established. The treatment groups were administered low, medium, and high doses of BYHWD, as well as broad-spectrum antibiotics. The effects of BYHWD on the vulnerable plaque area in the aorta, collagen content, macrophage and α-SMA protein expression, levels of inflammatory cytokines, reactive oxygen species (ROS), LC3 and NLRP3 expression, gut microbiota composition and abundance, serum trimethylamine-N-oxide (TMAO) levels, and the total bile acid content in the liver, serum, and gallbladder, as well as mitochondrial autophagy, were evaluated applying hematoxylin-eosin (HE) staining, Oil Red O staining, Sirius Red staining, immunohistochemistry, ELISA, immunofluorescence, 16S rRNA sequencing, biochemical analysis, and LC-MS detection. Western blot for TLR4, MyD88, ASC, pro-caspase-1, caspase-1, NLRP3, p-NF-κB/NF-κB, GPR41, GPR43, CYP7A1, CYP27A1, FMO3, FXR, TGR5, NIX, BNIP3, FUNDC1, PINK1, and Parkin proteins expression level.

A total of 31 major active components were identified in Buyang Huanwu Decoction (BYHWD). BYHWD significantly reduced the vulnerable plaque area in the ApoE-/- mouse model of AS, decreased the expression of inflammatory cytokines, inhibited the protein expression of TLR4, MyD88, p-NF-κB/NF-κB, ASC, pro-caspase-1, NLRP3, FMO3, NIX, BNIP3, FUNDC1, and PINK1/Parkin in aortic tissues, downregulated ROS levels and mitochondrial autophagy activity, regulated gut microbiota abundance, reduced serum TMAO levels, and up-regulated the expression of gut microbiota-related proteins, including GPR41, GPR43, CYP7A1, CYP27A1, FXR, and TGR5.

BYHWD exerts anti-AS effects through the inhibition of the TLR4/NF-κB/NLRP3 inflammatory pathway, modulating the gut microbiota, and stabilizing mitochondrial autophagy. The in-depth investigation of this mechanism effectively expands the therapeutic potential of BYHWD in the prevention and treatment of cardiovascular diseases and provides new theoretical insights and therapeutic targets for AS-related research.

The gut microbiota plays an essential role in regulating overall physiology, including metabolism and neurological and immune functions. Therefore, their dysregulation is closely associated with metabolic disorders, such as obesity and diabetes, as well as other pathological conditions, including inflammatory bowel diseases, cancer, and neurological disorders. Probiotics are commonly used to maintain a healthy gut microbiome, but their oral delivery is inefficient mainly due to their poor stability in the harsh gastrointestinal (GI) environment. This work presents an innovative encapsulation strategy, inspired by the natural structure of an egg, for the effective oral delivery of probiotics, termed PIE (Probiotics-In-Egg). The PIE technology is based upon encapsulating probiotics with phosvitin and ovalbumin derived from egg yolk and egg white, respectively. PIE exhibits significantly enhanced survival and proliferation in a simulated GI tract, as well as the ability to neutralize harmful reactive oxygen species (ROS) and sustain in nutrient-depleted conditions. Moreover, when administered orally in mouse models, PIE demonstrates excellent bioavailability and enhanced colonization in the GI tract. This egg-inspired encapsulation technology has great potential as a practical and effective platform for oral delivery of probiotics, which can significantly help maintain a healthy gut microbiome.

Diabetic nephropathy (DN) is one of the most serious and prevalent complications associated with diabetes. Consequently, antidiabetic drugs or foods potentially protecting the kidneys are of significant therapeutic value. Sulforaphene (SFE) is a natural isothiocyanate derived from radish seeds, known for its anti-inflammatory and antioxidant properties. However, no studies have investigated on the ability of SFE to prevent or treat DN. This study established a high-fat diet combined with a streptozotocin-induced type II diabetes mellitus mouse model. We administered SFE treatment to examine its protective effects on renal and intestinal homeostasis in DN mice. After 4 weeks of treatment, SFE (50 mg/kg b.w.) not only reduced blood glucose concentration (20.3 %, P < 0.001), kidney to body weight ratio (26.2 %, P < 0.01), and levels of serum total cholesterol (40.6 %, P < 0.001), triglycerides (38.2 %, P < 0.01), creatinine (36.7 %, P < 0.01), and urea nitrogen (45.0 %, P < 0.001) in DN mice compared to control mice but also increased the kidney superoxide dismutase (72.7 %, P < 0.001), catalase (51.1 %, P < 0.001), and glutathione peroxidase activities (31.6 %, P < 0.01), as well as glutathione levels (39.2 %, P < 0.01) in comparison to DN mice. Furthermore, SFE decreased levels of reactive oxygen species (55.4 %, P < 0.01), 4-hydroxyalkenals (36.9 %, P < 0.001), malondialdehyde (42.6 %, P < 0.001), and 8-hydroxy-deoxyguanosine (26.3 %, P < 0.001), accompanied by a meliorating kidney morphological abnormalities. Notably, a reduction in renal inflammatory factors was also observed in SFE-treated DN mice compared to untreated DN mice, particularly in the C-X-C motif chemokine ligand 8 factors (54.8 %, P < 0.001). Western blotting results indicated that SFE significantly down-regulated the protein expression of TLR4 and MyD88 (1.9, 1.7-fold, P < 0.001). Additionally, SFE improved gut microbiota (GM) dysbiosis and intestinal homeostasis, as evidenced by increased expression of antimicrobial peptides and tight junction proteins in colon tissue. SFE appeared to enhance the proliferation of probiotics, such as Bacteroidota, Lachnospiraceae_NK4A136_group and norank_f__Muribaculaceae, while also decreasing harmful bacteria to a greater extent compared to STZ treatment. These findings suggest that SFE modulates GM and improves intestinal homeostasis, providing a theoretical basis for its use in the treatment of DN.

Atherosclerosis is a closely related complication of diabetes mellitus (DM), driven by endothelial dysfunction, inflammation, and oxidative stress. The progression of atherosclerosis is accelerated by hyperglycemia, insulin resistance, and hyperlipidemia. Novel antidiabetic agents, SGLT2 inhibitors, and GLP-1 agonists improve glycemic control and offer cardiovascular protection, reducing the risk of major adverse cardiovascular events (MACEs) and heart failure hospitalization. These agents, along with nonsteroidal mineralocorticoid receptor antagonists (nsMRAs), promise to mitigate metabolic disorders and their impact on endothelial function, oxidative stress, and inflammation. This review explores the potential molecular mechanisms through which these drugs may prevent the development of atherosclerosis and cardiovascular disease (CVD), supported by a summary of preclinical and clinical evidence.

The Mediterranean diet (MD) is widely recognized for its health benefits, particularly in modulating gut microbiota composition and reducing the risk of metabolic, cardiovascular, and neurodegenerative diseases. Characterized by a high intake of plant-based foods, monounsaturated fats, and polyphenols, primarily from extra virgin olive oil, the MD fosters the growth of beneficial gut bacteria such as Bifidobacterium, Faecalibacterium prausnitzii, and Roseburia, which produce short-chain fatty acids that enhance gut barrier integrity, reduce inflammation, and improve metabolic homeostasis. Clinical and preclinical studies have proved that the MD is associated with increased microbial diversity, reduced pro-inflammatory bacteria, and improved markers of insulin sensitivity, lipid metabolism, and cognitive function. Additionally, the MD positively influences the gut microbiota in various conditions, including obesity, cardiovascular disease, and neurodegeneration, potentially mitigating systemic inflammation and enhancing neuroprotective mechanisms. Emerging evidence suggests that MD variants, such as the Green-MD, and their integration with probiotics can further optimize gut microbiota composition and metabolic parameters. While the beneficial impact of the MD on the gut microbiota and overall health is well supported, further long-term clinical trials are needed to better understand individual variability and improve dietary interventions tailored to different populations.

Diabetes mellitus (DM) is a significant global health issue, associated with various microvascular and macrovascular complications that significantly impair patients' quality of life as well as healthspan and lifespan. Despite the availability of several anti-diabetic medications with different mechanisms of action, there remains no definite curative treatment. Hence, discovering new efficient complementary therapies is essential. Natural products have received significant attention due to their advantages in various pathological conditions. Resveratrol is a natural polyphenol that possesses antioxidant and anti-inflammatory properties, and its efficacy has been previously investigated in several diseases, including DM. Herein, we aimed to provide a holistic view of the signaling pathways and mechanisms of action through which resveratrol exerts its effects against DM and its complications.

Humans consume large amounts of non-starch polysaccharides(NPs) daily. Some NPs, not absorbed by the body, proceed to the intestines. An increasing number of studies reveal a close relationship between NPs and gut microbiota(GM) that impact the human body. This review not only describes in detail the structures of several common NPs and their effects on GM, but also elucidates the degradation mechanisms of NPs in the intestine. The purpose of this review is to elucidate how NPs interact with GM in the intestine, which can provide valuable information for further studies of NPs.

Polycystic ovary syndrome (PCOS) is a complex disorder that significantly impacts female reproductive health and increases the risk of metabolic and reproductive diseases. Emerging evidence suggests that alterations in gut microbiota and their metabolic activities contribute to PCOS pathogenesis, although the underlying mechanisms remain elusive. In the current study, we found that patients with PCOS had altered metabolic profiles, particularly characterized by reduced levels of indole-3-propionic acid (IPA). Administration of IPA alleviated dehydroepiandrosterone (DHEA)-induced PCOS in mice, as demonstrated by improved estrus cycle, insulin sensitivity, ovarian morphology and hormone levels. Additionally, IPA treatment alleviated DHEA-induced oxidative stress in the ovaries and enhanced thermogenesis in brown adipose tissue. Furthermore, IPA attenuated DHEA-induced inflammation both in vivo and in vitro. Mechanistically, IPA treatment suppressed DHEA-induced inflammatory responses and inhibited NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation by activating the aryl hydrocarbon receptor (AhR). Collectively, our findings indicate that IPA ameliorates DHEA-induced PCOS through modulation of the AhR-NLRP3 pathway in mice, suggesting that regulating gut microbial tryptophan metabolism and AhR activation may represent a promising therapeutic strategy for PCOS prevention.

Peripheral neuropathy (PN), a complication of diabetes and obesity, progresses through a complex pathophysiology. Lifestyle interventions to manage systemic metabolism are recommended to prevent or slow PN, given the multifactorial risks of diabetes and obesity. A high-fat diet rich in saturated fatty acids (SFAs) induces PN, which a diet rich in monounsaturated fatty acids (MUFAs) rescues, independent of weight loss, suggesting factors beyond systemic metabolism impact nerve health. Interest has grown in gut microbiome mechanisms in PN, which is characterized by a distinct microbiota signature that correlates with sciatic nerve lipidome.

Herein, we postulated that SFA- versus MUFA-rich diet would impact gut microbiome composition and correlate with PN development. To assess causality, we performed fecal microbiota transplantation (FMT) from donor mice fed SFA- versus MUFA-rich diet to lean recipient mice and assessed metabolic and PN phenotypes.

We found that the SFA-rich diet altered the microbiome community structure, which the MUFA-rich diet partially reversed. PN metrics correlated with several microbial families, some containing genera with feasible mechanisms of action for microbiome-mediated effects on PN. SFA and MUFA FMT did not impact metabolic phenotypes in recipient mice although SFA FMT marginally induced motor PN.

The involvement of diet-mediated changes in the microbiome on PN and gut-nerve axis may warrant further study.

This study aims to investigate the characteristics of gut microbiota in patients with microvascular complications of Type 2 Diabetes Mellitus (T2DM) using 16S rRNA high-throughput sequencing technology.

Patients diagnosed with T2DM were enrolled as study subjects. Based on the presence of microvascular complications, subjects were divided into a study group, a control group. Clinical fecal samples from the two groups were subjected to diversity analysis using the Illumina MiSeq high-throughput sequencing technology, comparing the richness and diversity of the gut microbiota between the two groups. The Tax4Fun software was utilized for the functional prediction of differential microbiota.

A total of 3727 operational taxonomic units (OTUs) were identified, with 1311 OTUs common to both groups, and 1363 and 1053 OTUs unique to the study group and the control group, respectively. The study group exhibited a significant increase in the relative abundance of Clostridia and Negativicutes, and a marked decrease in Gammaproteobacteria, Bacilli, and Verrucomicrobia compared to the control group. LefSe analysis revealed significant differences in the relative abundance at two phyla, two classes, two orders, three families, and two genera levels between the groups. KEGG pathway analysis of differential microbiota identified 10 pathways with statistically significant differences (P<0.05).

This study reveals significant disparities in gut microbiota abundance between T2DM patients and those with microvascular complications of T2DM, suggesting potential microbial markers for diagnosing and treating microvascular complications of T2DM.

The human gut microbiota, a complex and diverse community of microorganisms, plays a crucial role in maintaining overall health by influencing various physiological processes, including digestion, immune function, and disease susceptibility. The balance between beneficial and harmful bacteria is essential for health, with dysbiosis - disruption of this balance - linked to numerous conditions such as metabolic disorders, autoimmune diseases, and cancers. This review highlights key genera such as Enterococcus, Ruminococcus, Bacteroides, Bifidobacterium, Escherichia coli, Akkermansia muciniphila, Firmicutes (including Clostridium and Lactobacillus), and Roseburia due to their well-established roles in immune regulation and metabolic processes, but other bacteria, including Clostridioides difficile, Salmonella, Helicobacter pylori, and Fusobacterium nucleatum, are also implicated in dysbiosis and various diseases. Pathogenic bacteria, including Escherichia coli and Bacteroides fragilis, contribute to inflammation and cancer progression by disrupting immune responses and damaging tissues. The potential for microbiota-based therapies, such as probiotics, prebiotics, fecal microbiota transplantation, and dietary interventions, to improve health outcomes is examined. Future research directions in the integration of multi-omics, the impact of diet and lifestyle on microbiota composition, and advancing microbiota engineering techniques are also discussed. Understanding the gut microbiota's role in health and disease is essential for formulating personalized, efficacious treatments and preventive strategies, thereby enhancing health outcomes and progressing microbiome research.

Painful diabetic neuropathy (PDN) is one of the most common complications of diabetes. Recent studies suggested that gut microbiota dysbiosis contributes to the development of PDN, but underlying mechanisms remain elusive. In this study, we found decreased probiotics generating bacteria such as Lactobacillus and Bifidobacterium strains in the PDN rats. Supplementation with multiple probiotics for 12 weeks alleviated pain, reversed nerve fiber lesions, and restored neuronal hyperexcitability. Probiotics administration effectively attenuated intestinal barrier impairment, reduced serum lipopolysaccharide and proinflammatory cytokines, and mitigated disruptions in the blood-nerve barrier. Furthermore, probiotics treatment inhibited the activation of the TLR4/MyD88/NF-κB signaling pathway and reduced proinflammatory cytokines in the sciatic nerve of the PDN rats. Together, our findings suggest that gut microbiota dysbiosis participates in PDN pathogenesis, and probiotics offer therapeutic potential via modulating the microbiota-gut-nerve axis.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterised by lipid accumulation in the liver and is often associated with obesity and type 2 diabetes. The gut microbiome recently emerged as a significant player in liver metabolism and health. Hippurate, a host-microbial co-metabolite has been associated with human gut microbial gene richness and with metabolic health. However, its role on liver metabolism and homeostasis is poorly understood.

We characterised liver biospies from 318 patients with obesity using RNAseq and metabolomics in liver and plasma to derive associations among hepatic hippurate, hepatic gene expression and MASLD and phenotypes. To test a potential beneficial role for hippurate in hepatic insulin resistance, we profile the metabolome of (IHH) using ultra-high-performance liquid chromatography coupled to high-resolution tandem mass spectrometry (UHPLC-MS/MS), and characterised intracellular triglyceride accumulation and glucose internalisation after a 24 h insulin exposure.

We first report significant associations among MASLD traits, plasma and hepatic hippurate. Further analysis of the hepatic transcriptome shows that liver and plasma hippurate are inversely associated with MASLD, implicating lipid metabolism and regulation of inflammatory responses pathways. Hippurate treatment inhibits lipid accumulation and rescues insulin resistance induced by 24-hour chronic insulin in IHH. Hippurate also improves hepatocyte metabolic profiles by increasing the abundance of metabolites involved in energy homeostasis that are depleted by chronic insulin treatment while decreasing those involved in inflammation.

Altogether, our results further highlight hippurate as a mechanistic marker of metabolic health, by its ability to improve metabolic homeostasis as a postbiotic candidate.

 The parasite Toxoplasma gondii is the source of toxoplasmosis. This infection can spread from mother to fetus during pregnancy, through contaminated food or water, or contact with infected cat feces. This study aims to investigate whether chronic toxoplasmosis is associated with an increased risk of type 2 diabetes mellitus (T2DM) in women.

A total of 274 samples were collected from women of reproductive age (18-55 years) as they were relevant for both chronic toxoplasmosis and T2DM. Serological testing was performed to detect the presence of T. gondii antibodies (IgM and IgG) to assess chronic infection, and fasting plasma glucose and HbA1c levels were measured for T2DM diagnosis.

Among the participants, 46 (16.8%) were seropositive for chronic toxoplasmosis, and 68 (24.8%) were diagnosed with T2DM. Statistical analysis revealed that women with chronic toxoplasmosis were 2.3 times more likely to have T2DM compared to women without toxoplasmosis (OR = 2.289, CI: 1.171-4.473, p-value < 0.05). The study also found a significant association between education level and T2DM, with educated women being at lower risk of having T2DM (p-value < 0.05).

This study highlights a statistically significant association between chronic toxoplasmosis and T2DM. Women who were seropositive for chronic toxoplasmosis were more likely to have T2DM compared to seronegative individuals. These findings contribute to the growing body of evidence suggesting a potential link between chronic infections and metabolic disorders. Further research is needed to establish causation, elucidate underlying mechanisms, and explore potential interventions to mitigate the risk of T2DM in individuals with chronic toxoplasmosis.

This case report presents a 46-year-old woman with type 2 diabetes mellitus (T2DM) who sought to discontinue glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) therapy while maintaining her weight and metabolic health. Her desire to reduce medication dependency, combined with her apprehension about potential metabolic regression following discontinuation of the drug, highlights a challenge often faced by patients managing chronic conditions, and the value of naturopathic adjunctive therapies to support these individuals in their wellness goals. This report details a comprehensive intervention strategy combining probiotics, nutrient supplementation, and lifestyle modifications to address her concerns. Over an 8-week period post-GLP-1 RAs therapy discontinuation, she maintained weight loss, improved glycemic control and lipid profile, demonstrated improvements in micronutrient levels, and experienced improvements in her quality of life. This case contributes to the growing body of evidence suggesting that targeted naturopathic interventions can play a supportive role in managing T2DM and mitigating the reliance on pharmacotherapy without compromising health outcomes.

Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated diarrhea. The infection is associated with a high mortality rate and risk of recurrence. We assessed risk factors for death or recurrent CDI (CDI) in patients with diabetes mellitus (DM).

This retrospective cohort study was conducted at a single institution from 2019 to 2020. CDI was defined as a positive toxin assay for C. difficile. CDI was defined as a repeat positive toxin assay within ≤ 60 days of stopping CDI treatment. Logistic regression models were used to identify risk factors for CDI-related mortality, recurrence, and the combined outcome of mortality and recurrence.

Of the 252 enrolled patients with CDI, 19% had DM. Only 49% of patients with DM fully recovered after the first CDI occurrence, whereas 69% of patients without diabetes fully recovered (p = 0.021); 23% of patients with DM vs. 17% of patients without DM had recurrences (p = 0.200); and 23% of patients with DM vs. 15% of patients without DM died (p = 0.169). DM was associated with mortality (OR 2.75, 95% CI 0.94-8.06) and the combined outcome (OR 2.10, 95% CI 1.05-4.18). Nosocomial transmission, immunosuppression, CKD, and age were associated with mortality.

Diabetes is associated with a worse prognosis in patients with CDI. Prevention efforts should be optimized in patients with diabetes by reducing CDI transmission and avoiding nonessential medications, such as PPIs or antibiotics when they are not necessary. [Figure: see text].

A close relationship between the pathogenesis of chronic kidney disease (CKD) and abnormalities in the gut-kidney axis. Paotianxiong polysaccharides (PTXP) that have demonstrated therapeutic effects on CKD. However, the specific mechanism by which PTXP ameliorates CKD through the gut-kidney axis remains to be explored. In this study, the microbiomes and metabolomics were combined to investigate the impact of PTXP on intestinal flora structure and metabolism, further unveiling the relationship through correlation analysis. The results showed that PTXP intervention significantly modulated renal function abnormalities in CKD rats and significantly modulates gut microbial disorders, evidenced by an increased abundance of Lactobacillus murinus, Bacteroides fragilis, and a decreased abundance of Bifidobacterium pseudolongum. Furthermore, PTXP reversed the changes in intestinal metabolites, such as linoleic acid and docosahexaenoic acid, induced by CKD and identified unsaturated fatty acid metabolism as a key metabolic pathway. Correlation analyses also revealed associations among gut microorganisms, metabolites, and renal function indexes, confirming that PTXP alleviated CKD through the gut-kidney axis. Moreover, the above conclusions were verified by fecal bacteria transplantation experiments. These findings provide insights into the mechanism of PTXP for the treatment of CKD and provide new targets for the treatment of CKD.

Diabetes, a chronic condition affecting millions of individuals, is divided into type 1 diabetes (T1D) and type 2 diabetes (T2D), each with unique pathophysiological characteristics. While the impact of diabetes on vision is established, its relationship with other special senses, balance, hearing, and olfaction, remains uncertain. This study utilized a 2-sample Mendelian randomization (MR) approach to investigate the associations between diabetes subtypes and specific sensory disorders. We performed MR analysis using various methods (inverse variance weighting [IVW], MR-Egger, simple mode, weighted mode, weighted median, MR-PRESSO) to assess the causal relationships between diabetes subtypes and sensory disorders (vestibular dysfunction, sensorineural hearing loss, conductive hearing loss, and olfactory dysfunction). Different diabetes genome-wide association studies datasets were utilized for validation. MR analysis revealed no significant correlations between T1D or T2D and the sensory disorders studied. Interestingly, an initial signal suggested that T1D might increase the risk of conductive hearing loss (IVW: odds ratio = 1.120, 95% CI: 1.035-1.211, P = .005), but this finding was not supported by validation studies. No evidence of horizontal pleiotropy or heterogeneity was found (P > .05). Our MR analysis and subsequent validation revealed no significant associations between diabetes subtypes and special senses. The initial suggestion of an increased risk of conductive hearing loss in T1D patients was not confirmed. Future research should further explore the intricate relationships among diabetes, sensory functions, and other factors, as well as the potential effects of diabetes management on sensory health.

It is well known that gut microbial imbalance is a potential factor for the occurrence and development of diabetes mellitus (DM) and its complications. Moreover, the heart and gut microbiota can regulate each other through the gut-metabolite-heart axis. In this study, metagenomics, metabolomics, and transcriptomics were chosen to sequence the changes in gut microbiota, serum metabolite levels, and differentially expressed genes (DEGs) in leptin receptor-deficient db/db mice and analyze the correlation between serum metabolites and gut microbiota or DEGs. According to the results, there were significant differences in the 1,029 cardiac genes and 353 serum metabolites in diabetic mice of the db/db group, including DEGs enriched in the PPAR signaling pathway and increased short-chain carboxylic acids (CAs), when compared with the normal db/m group. According to metagenomics, the gut microbiota of mice in the db/db group were disrupted, and particularly Lachnospiraceae bacteria and Oscillospiraceae bacteria significantly decreased. Also, according to the Pearson correlation analysis, a significant positive correlation was found between CAs and PPAR signaling pathway-related DEGs, and a negative correlation was found between CAs and the abundance of the above-mentioned species. To sum up, type 2 diabetes mellitus (T2DM) can upregulate the expression of partial cardiac genes through the levels of serum short-chain CAs affected by gut microbiota, thus playing a role in the occurrence and development of diabetic cardiomyopathy (DCM).

Our research results clearly link the changes in heart genes of T2DM and normal mice with changes in serum metabolites and gut microbiota, indicating that some genes in biological processes are closely related to the reduction of protective microbiota in the gut microbiota. This study provides a theoretical basis for investigating the mechanism of DCM and may provide preliminary evidence for the future use of gut microbiota therapy for DCM.

The absence of suitable intervention significantly increases the likelihood of type 2 diabetes mellitus (T2DM) development in people with prediabetes. Recent statistical findings indicate that the gut microbiome might influences the development of insulin resistance. The objective of our study was to assess the efficacy and safety of probiotic supplementation in individuals diagnosed with prediabetes. A thorough search was carried out on the Cochrane Library, Medline, Scopus, and ClinicalTrials.gov databases until September 12th, 2024, using a mix of pertinent keywords. This review incorporates randomized clinical trials (RCTs) concerning the effect of probiotics for prediabetes. We used random-effect models to examine the mean difference (MD). A total of eight RCTs were incorporated. The results of our meta-analysis indicated that probiotics supplementation was associated with higher reduction in hemoglobin A1c (HbA1c) (MD -0.07% (95% CI -0.11, -0.03), p = 0.0005, I2 = 0%) among individuals with prediabetes when compared to placebo. Other indicators such as total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and body mass index (BMI) did not differ significantly between probiotics and placebo. No significant difference was observed in the occurrence of adverse events (AEs) between the two groups. This study indicates the efficacy and safety of probiotics supplementation to improve the glycemic parameters in patients with prediabetes.

Polysaccharide extracted from Grifola frondosa (GFP) was selected in this study. After preliminary separation, four factions were collected, named GFP-F1, GFP-F2, GFP-F3 and GFP-F4. GPF-F2 was further separated into two fractions, namely GFP-N1 and GFP-N2. The molecular weight of GFP-N1 and GFP-N2 was 3.323×103 kDa and 10.8 kDa, respectively. GFP-N1 was composed of glucose and galactose and 1 → 3, 1 → 4, and 1 → 6 glycosidic bonds. GFP-N2 was composed of glucose, galactose and mannose and 1 → 2, 1 → 3, 1 → 4, and 1 → 6 glycosidic bonds. GFP could significantly relieve the insulin resistance induced by HFD. GFP significantly alleviated gut microbiota disturbance caused by HFD and increased the production of short-chain fatty acids, and further reduced the expression of LPS/TLR4 inflammatory pathway. GFP significantly reduced the oxidative stress induced by HFD, increased the expression of the Nrf2/ARE signaling pathway. These results indicated that GFP could be developed as a potential ingredient for the management of insulin resistance.

The human oral and nasal microbiota contains approximately 770 cultivable bacterial species. More than 2,000 genome sequences of these bacteria can be found in the expanded Human Oral Microbiome Database (eHOMD). We developed HOMDscrape, a freely available Python software tool to programmatically retrieve and process amino acid sequences and sequence identifiers from BLAST results acquired from the eHOMD website. Using the data obtained through HOMDscrape, the phylogeny of proteins involved in bacterial type 9 secretion system (T9SS)-driven gliding motility, flagellar motility, and type IV pilus-driven twitching motility was constructed. A comprehensive phylogenetic analysis was conducted for all components of the rotary T9SS, a machinery responsible for secreting various enzymes, virulence factors, and enabling bacterial gliding motility. Results revealed that the T9SS outer membrane β-barrel protein SprA of human oral bacteria underwent horizontal evolution. Overall, we catalog motile bacteria that inhabit the human oral microbiota and document their evolutionary connections. These results will serve as a guide for further studies exploring the impact of motility on the shaping of the human oral microbiota.IMPORTANCEThe human oral microbiota has been extensively studied, and many of the isolated bacteria have genome sequences stored on the human oral microbiome database (eHOMD). Spatial distribution and polymicrobial biofilms are observed in the oral microbiota, but little is understood on how they are influenced by motility. To bridge this gap, we developed a software tool to identify motile bacteria from eHOMD. The results enabled the cataloging of motile bacteria present in the oral microbiota but also provided insight into their evolutionary relationships. This information can guide future research to better understand how bacterial motility shapes the human oral microbiota.

Recent research has suggested imbalances in gut microbiota composition as contributors to cardiac aging. An individual's physical condition, along with lifestyle-associated factors, including diet and medication, are significant determinants of gut microbiota composition. This review discusses evidence of bidirectional associations between aging and gut microbiota, identifying gut microbiota-derived metabolites as potential regulators of cardiac aging. It summarizes the effects of gut microbiota on cardiac aging diseases, including cardiac hypertrophy and fibrosis, heart failure, and atrial fibrillation. Furthermore, this review discusses the potential anti-aging effects of modifying gut microbiota composition through dietary and pharmacological interventions. Lastly, it underscores critical knowledge gaps and outlines future research directions. Given the current limited understanding of the direct relationship between gut microbiota and cardiac aging, there is an urgent need for preclinical and clinical investigations into the mechanistic interactions between gut microbiota and cardiac aging. Such endeavors hold promise for shedding light on the pathophysiology of cardiac aging and uncovering new therapeutic targets for cardiac aging diseases.

There is a significant global demand for precise diagnosis and effective treatment of IgA nephropathy (IgAN), with innate immunity, particularly the complement system, exerting a profound influence on its pathogenesis. Additionally, the gut-kidney axis pathway is vital in the emergence and development of IgAN.

We conducted a comprehensive search in the Web of Science database, spanning from January 1, 2000 to December 18, 2023. The gathered literature underwent a visual examination through CiteSpace, VOSviewer, and Scimago Graphica to delve into authors, nations, organizations, key terms, and other pertinent elements.

Between 2000 and 2023, a total of 720 publications were identified, out of which 436 publications underwent screening for highly relevant literature analysis. The average annual number of articles focusing on IgAN, innate immunity, and the gut-kidney axis is approximately 31, with an upward trend observed. In terms of research impact encompassing publication count and authorship, the United States emerged as the leading contributor. Prominent keywords included "complement", "activation", "microbe", "gut-kidney axis", "C4d deposition", "alternative pathway" and "B cells" along with other prospective hot topics.

The correlation between IgAN and innate immunity is a focal point in current scientific research. Recent literature underscores the significance of the gut-kidney axis, where intestinal microorganisms and metabolites may influence IgAN. The complement system, a key component of innate immunity, also has a crucial function.Advancements in prevention, diagnosis, and treatment hinge on unraveling this intricate relationship.

Extensive research has underscored the criticality of preserving diversity and equilibrium within the gut microbiota for optimal human health. However, the precise mechanisms by which the metabolites and targets of the gut microbiota exert their effects remain largely unexplored. This study utilizes a network pharmacology methodology to elucidate the intricate interplay between the microbiota, metabolites, and targets in the context of DM, thereby facilitating a more comprehensive comprehension of this multifaceted disease.

In this study, we initially extracted metabolite information of gut microbiota metabolites from the gutMGene database. Subsequently, we employed the SEA and STP databases to discern targets that are intricately associated with these metabolites. Furthermore, we leveraged prominent databases such as Genecard, DisGeNET, and OMIM to identify targets related to diabetes. A protein-protein interaction (PPI) network was established to screen core targets. Additionally, we conducted comprehensive GO and KEGG enrichment analyses utilizing the DAVID database. Moreover, a network illustrating the relationship among microbiota-substrate-metabolite-target was established.

We identified a total of 48 overlapping targets between gut microbiota metabolites and diabetes. Subsequently, we selected IL6, AKT1 and PPARG as core targets for the treatment of diabetes. Through the construction of the MSMT comprehensive network, we discovered that the three core targets exert therapeutic effects on diabetes through interactions with 8 metabolites, 3 substrates, and 5 gut microbiota. Additionally, GO analysis revealed that gut microbiota metabolites primarily regulate oxidative stress, inflammation and cell proliferation. KEGG analysis results indicated that IL-17, PI3K/AKT, HIF-1, and VEGF are the main signaling pathways involved in DM.

Gut microbiota metabolites primarily exert their therapeutic effects on diabetes through the IL6, AKT1, and PPARG targets. The mechanisms of gut microbiota metabolites regulating DM might involve signaling pathways such as IL-17 pathways, HIF-1 pathways and VEGF pathways.

Microbial signatures in the human microbiome are closely associated with various human diseases, driving the development of machine learning models for microbiome-based disease prediction. Despite progress, challenges remain in enhancing prediction accuracy, generalizability, and interpretability. Confounding factors, such as host's gender, age, and body mass index, significantly influence the human microbiome, complicating microbiome-based predictions.

To address these challenges, we developed MicroKPNN-MT, a unified model for predicting human phenotype based on microbiome data, as well as additional metadata like age and gender. This model builds on our earlier MicroKPNN framework, which incorporates prior knowledge of microbial species into neural networks to enhance prediction accuracy and interpretability. In MicroKPNN-MT, metadata, when available, serves as additional input features for prediction. Otherwise, the model predicts metadata from microbiome data using additional decoders. We applied MicroKPNN-MT to microbiome data collected in mBodyMap, covering healthy individuals and 25 different diseases, and demonstrated its potential as a predictive tool for multiple diseases, which at the same time provided predictions for the missing metadata. Our results showed that incorporating real or predicted metadata helped improve the accuracy of disease predictions, and more importantly, helped improve the generalizability of the predictive models.

https://github.com/mgtools/MicroKPNN-MT.

Sirt6, reactive oxygen species and ferroptosis may participate in the pathogenesis of Diabetic Nephropathy (DN). Exploring the relationship between Sirt6, oxidative stress, and ferroptosis provides new scientific ideas to DN.

Human podocytes were stimulated with 30 mM glucose and 5.5 mM glucose. The mice of db/db group were randomly divided into two groups:12 weeks and 16 weeks. Collect mouse blood and urine specimens and renal cortices for investigations. HE, Masson, PAS and immunohistochemical staining were used to observe pathological changes. Western blot, RT-qPCR and immunofluorescence staining were used to evaluate expression of relevant molecules. CCK8 method was introduced to observe cell viability. The changes of podocyte mitochondrial membrane potential and mitochondrial morphology in each group were determined by JC-1 staining and Mito-Tracker.

The expression level of Sirt6, Nrf2, SLC7A11, HO1, SOD2 and GPX4 were reduced, while ACSL4 was increased in DN. Blood glucose, BUN, Scr, TG, T-CHO and 24h urine protein were upregulated, while ALB was reduced in diabetic group. The treatment of Ferrostatin-1 significantly improved these changes, which proved ferroptosis was involved in the development of DN. Overexpression of Sirt6 might ameliorate the oxidation irritable reaction and ferroptosis. Sirt6 plasmid transfection increased mitochondrial membrane potential and protected morphology and structure of mitochondria. The application of Sirt6 siRNA could aggravated the damage manifestations.

High glucose stimulation could decrease the antioxidant capacity and increase formation of ROS and lipid peroxidation. Sirt6 might alleviate HG-induced mitochondrial dysfunction, podocyte injury and ferroptosis through regulating Nrf2/GPX4 pathway.

Gut microorganism (GM) is an integral component of the host microbiome and health system. Abuse of antibiotics disrupts the equilibrium of the microbiome, affecting environmental pathogens and host-associated bacteria alike. However, relatively little research on Bacillus licheniformis alleviates the adverse effects of antibiotics. To test the effect of B. licheniformis as a probiotic supplement against the effects of antibiotics, cefalexin was applied, and the recovery from cefalexin-induced jejunal community disorder and intestinal barrier damage was investigated by pathology, real-time PCR (RT-PCR), and high-throughput sequencing (HTS). The result showed that A group (antibiotic treatment) significantly reduced body weight and decreased the length of jejunal intestinal villi and the villi to crypt (V/C) value, which also caused structural damage to the jejunal mucosa. Meanwhile, antibiotic treatment suppressed the mRNA expression of tight junction proteins ZO-1, claudin, occludin, and Ki67 and elevated MUC2 expression more than the other Groups (P < 0.05 and P < 0.01). However, T group (B. licheniformis supplements after antibiotic treatment) restored the expression of the above genes, and there was no statistically significant difference compared to the control group (P > 0.05). Moreover, the antibiotic treatment increased the relative abundance of 4 bacterial phyla affiliated with 16 bacterial genera in the jejunum community, including the dominant Firmicutes, Proteobacteria, and Cyanobacteria in the jejunum. B. licheniformis supplements after antibiotic treatment reduced the relative abundance of Bacteroidetes and Proteobacteria and increased the relative abundance of Firmicutes, Epsilonbacteraeota, Lactobacillus, and Candidatus Stoquefichus. This study uses mimic real-world exposure scenarios by considering the concentration and duration of exposure relevant to environmental antibiotic contamination levels. We described the post-antibiotic treatment with B. licheniformis could restore intestinal microbiome disorders and repair the intestinal barrier. KEY POINTS: • B. licheniformis post-antibiotics restore gut balance, repair barrier, and aid health • Antibiotics harm the gut barrier, alter structure, and raise disease risk • Long-term antibiotics affect the gut and increase disease susceptibility.

Type 2 diabetes (T2D) pathophysiology involves insulin resistance (IR) and inadequate insulin secretion. Current T2D management includes dietary adjustments and/or oral medications such as thiazolidinediones (TZDs). Carrots have shown to contain bioactive acetylenic oxylipins that are partial agonists of the peroxisome proliferator-activated receptor γ (Pparg) that mimic the antidiabetic effect of TZDs without any adverse effects. TZDs exert hypoglycemic effects through activation of Pparg and through the regulation of the gut microbiota (GM) producing short-chain fatty acids (SCFAs), which impact glucose and energy homeostasis, promote intestinal gluconeogenesis, and influence insulin signaling pathways. This study investigated the metabolic effects of carrot intake in a T2D mouse model, elucidating underlying mechanisms. Mice were fed a low-fat diet (LFD), high-fat diet (HFD), or adjusted HFD supplemented with 10% carrot powder for 16 weeks. Oral glucose tolerance tests were conducted at weeks 0 and 16. Fecal, cecum, and colon samples, as well as tissue samples, were collected at week 16 during the autopsy. Results showed improved oral glucose tolerance in the HFD carrot group compared to HFD alone after 16 weeks. GM analysis demonstrated increased diversity and compositional changes in the cecum of mice fed HFD with carrot relative to HFD. These findings suggest the potential effect of carrots in T2D management, possibly through modulation of GM. Gene expression analysis revealed no significant alterations in adipose or muscle tissue between diet groups. Further research into carrot-derived bioactive compounds and their mechanisms of action is warranted for developing effective dietary strategies against T2D.

Over recent years, the prevalence of diabetes has been on the rise, paralleling improvements in living standards. Diabetic nephropathy (DN), a prevalent complication of diabetes, has also exhibited a growing incidence. While some clinical studies and reviews have hinted at a link between diabetic nephropathy and gut microbiota (GM), the nature of this connection, specifically its causative nature, remains uncertain. Investigating the causal relationship between diabetic nephropathy and gut microbiota holds the promise of aiding in disease screening and identifying novel biomarkers. In this study, we employed a two-sample Mendelian randomization analysis. Our dataset encompassed 4,111 DN patients from the GWAS database, juxtaposed with 308,539 members forming a control group. The aim was to pinpoint specific categories within the vast spectrum of the 211 known gut microbiota types that may have a direct causal relationship with diabetic nephropathy. Rigorous measures, including extensive heterogeneity and sensitivity analyses, were implemented to mitigate the influence of confounding variables on our experimental outcomes. Ultimately, our comprehensive analysis revealed 15 distinct categories of gut microbiota that exhibit a causal association with diabetic nephropathy. In summary, the phyla Bacteroidota and Verrucomicrobiae, the families Peptostreptococcaceae and Veillonellaceae, the genus Akkermansia, and the species Catenibacterium, Lachnoclostridium, Parasutterella, along with the orders Bacteroidales and Verrucomicrobiales, and the class Bacteroidetes were identified as correlates of increased risk for DN. Conversely, the family Victivallaceae, the species Eubacterium coprostanoligenes, and the Clostridium sensu stricto 1 group were found to be associated with a protective effect against the development of DN.These findings not only provide valuable insights but also open up novel avenues for clinical research, offering fresh directions for potential treatments.

Numerous studies have revealed a correlation between the risk of developing diabetic nephropathy (DN) and the gut microbiota (GM) composition. However, it remains uncertain whether the GM composition causes DN. We aimed to explore any potential causal links between the GM composition and the risk of developing DN. A meta-analysis conducted by the MiBioGen consortium of the largest genome-wide association study (GWAS) provided aggregated data on the GM. DN data were obtained from the IEU database. The inverse-variance weighting (IVW) method was employed as the primary analytical approach. The IVW analysis indicated that genus Dialister (OR = 0.51, 95% CI: 0.34-0.77, p = 0.00118) was protective against DN. In addition, class Gammaproteobacteria (OR = 0.47, 95% CI: 0.27-0.83, p = 0.0096), class Lentisphaeria (OR =0.76, 95% CI: 0.68-0.99, p = 0.04), order Victivallales (OR = 0.76, 95% CI: 0.58-0.99, p = 0.04), and phylum Proteobacteria (OR = 0.53, 95% CI: 0.33-0.85, p = 0.00872) were negatively associated with the risk of developing DN. Genus LachnospiraceaeUCG008 (OR =1.45, 95% CI: 1.08-1.95, p = 0.01), order Bacteroidales (OR = 1.59, 95% CI: 1.02-2.49, p = 0.04), and genus Terrisporobacter (OR = 1.98, 95% CI: 1.14-3.45, p = 0.015) were positively associated with the risk of developing DN. In this study, we established a causal relationship between the genus Dialister and the risk of developing DN. Further trials are required to confirm the protective effects of probiotics on DN and to elucidate the precise protective mechanisms involving genus Dialister and DN.

Diabetic neuropathy is a traditional and one of the most prevalent complications of diabetes mellitus. The exact pathophysiology of diabetic neuropathy is not fully understood. However, oxidative stress and inflammation are proven to be one of the major underlying mechanisms of neuropathy which is described in detail. Gut dysbiosis is being studied for various neurological disorders and its impact on diabetic neuropathy is also explained. Diabetic neuropathy also causes loss in an individual's quality of life and one such adverse event is cognitive dysfunction. The interrelation between the neuropathy, cognitive dysfunction and gut is reviewed.

The exact mechanism is not understood but several hypotheses, cross-sectional studies and systematic reviews suggest a relationship between cognition and neuropathy. The review has collected data from various review and research publications that justifies this inter-relationship.

The multifactorial etiology and pathophysiology of diabetic neuropathy is described with special emphasis on the role of gut dysbiosis. There might exist a correlation between the neuropathy and cognitive impairment caused simultaneously in diabetic patients.

This review summarizes the relationship that might exist between diabetic neuropathy, cognitive dysfunction and the impact of disturbed gut microbiome on its development and progression.