Gut Microbiota Imbalance Research Articles

Impact of Gut Microbiota on the Development of Diseases

Aim: The aim of this article is to review the latest scientific research on the influence of intestinal microbiota on the development of diseases. In this article we will discuss the importance of the intestinal microbiota, the differences in the composition of the microbiota between healthy and sick people and the relationship between the intestinal microbiota and metabolic, inflammatory, cardiovascular and neurodegenerative diseases. Abbreviated description of the state of knowledge: The gut microbiota plays a key role in human health by influencing the development and progression of various diseases. Numerous studies have shown that an imbalance in gut microbiota, called dysbiosis, may be linked to a number of conditions. Intestinal microflora interacts with the immune system, modulates inflammation and influences metabolic pathways, which emphasizes its importance in the development of diseases. Conclusions: Intestinal microflora is crucial to health, regulating immune, metabolic and neurological functions. Dysbiosis, i.e. disturbance of the balance of intestinal microflora, is associated with diseases such as type 2 diabetes, obesity, inflammatory bowel diseases, allergies, autoimmune diseases and neuropsychiatric disorders. Healthy microflora, influenced by diet, pH and nutrients, are essential for metabolism, immune system regulation and neuronal communication. Recently, scientists have become interested in the possibility of using this knowledge in treatment. Appropriate dietary management, probiotic supplementation and fecal microflora transplantation show promising potential. Future research should focus on elucidating the specific mechanisms by which the gut microbiota influences disease processes and developing targeted therapies to exploit the therapeutic potential of the microbiota.

Targeting Gut microbiota as a therapeutic target in T2DM: a review of Multi-target interactions of probiotics, prebiotics, postbiotics, and synbiotics with the Intestinal Barrier

The global epidemic of type 2 diabetes mellitus (T2DM) imposes a substantial burden on public health and healthcare expenditures, thereby driving the pursuit of cost-effective preventive and therapeutic strategies. Emerging evidence suggests a potential association between dysbiosis of gut microbiota and its metabolites with T2DM, indicating that targeted interventions aimed at modulating gut microbiota may represent a promising therapeutic approach for the management of T2DM. In this review, we concentrated on the multifaceted interactions between the gut microbiota and the intestinal barrier in the context of T2DM. We systematically summarized that the imbalance of beneficial gut microbiota and its metabolites may constitute a viable therapeutic approach for the management of T2DM. Meanwhile, the mechanisms by which gut microbiota interventions, such as probiotics, prebiotics, postbiotics, and synbiotics, synergistically improve insulin resistance in T2DM are summarized. These mechanisms include the restoration of gut microbiota structure, upregulation of intestinal epithelial cell proliferation and differentiation, enhancement of tight junction protein expression, promotion of mucin secretion by goblet cells, and the immunosuppressive functions of regulatory T cells (Treg) and M2 macrophages. Collectively, these actions contribute to the amelioration of the body's metabolic inflammatory status. Our objective is to furnish evidence that supports the clinical application of probiotics, prebiotics, and postbiotics in the management of T2DM.

The potential role of gut microbiota in the occurrence and development of endometriosis.

Endometriosis (EMT) has a significant impact on women's physical and mental health. In this study, high-throughput sequencing technology was employed to detect differences in gut microbiota between EMT patients and healthy individuals (CTL). Additionally, Spearman correlation analysis was utilized to analyze the correlation between different bacterial genera and EMT biomarkers (CA125 and CA199). The results demonstrated that at the phylum level, the relative abundances of Proteobacteria and Desulfobacterota_G_459546 in the EMT group were significantly higher than those in the CTL group, while the relative abundances of Bacteroidota and Firmicutes_A in the EMT group were significantly lower than those in the CTL group. At the genus level, the relative abundances of Burkholderiales and Sphingomonadales in the EMT group were significantly higher than those in the CTL group, while the relative abundances of Bacteroidales and Roseburia in the EMT group were significantly lower than those in the CTL group. The correlation analysis results show that CA125 and CA199 are significantly positively correlated with Burkholderiales and Sphingomonadales, and significantly negatively correlated with Bacteroidales, Oscillospirales, and Roseburia. The PICRUSt2 results show that the relative abundance in the cell motility and xenobiotics biodegradation and metabolism pathways in the EMT group was higher than that in the CTL group, while the relative abundance in the translation, replication and repair, folding, sorting and degradation, metabolism of terpenoids and polyketides and metabolism of cofactors and vitamins pathways in the EMT group was lower than that in the CTL group. In brief, there is a close correlation between the imbalance of gut microbiota and the onset of EMT. The intestinal microbiota has great significance broad prospects for the prevention, diagnosis and treatment of EMT.

Osa-miR168a, a Plant miRNA That Survives the Process of In Vivo Food Digestion, Attenuates Dextran Sulfate Sodium-Induced Colitis in Mice by Oral Administration.

Previous studies showed that osa-miR168a, a plant miRNA rich in fruits and vegetables, had cross-kingdom biological effects on immunocytes, silkworms, and rodents. In this study, the effects of miR168a on mouse colitis induced by dextran sulfate sodium (DSS) were investigated. The results showed that miR168a oligomers were resistant during the process of food digestion, ending up with a residual concentration of 67.8 ± 11.2 fM in mouse intestines 4 h after oral gavage. More importantly, direct oral administration of the miRNA to the colitis mice significantly ameliorated the progression of the disease, as evidenced by the reduction in DAI score, histopathological lesions, and proinflammatory cytokines. Repairing intestinal barrier function by promoting the regeneration of TJ proteins and the mucus layer, suppressing oxidative stress and colonic inflammation via modulating Nrf2 and NF-κB signaling pathways, and restoring the imbalanced gut microbiota caused by DSS are proposed mechanisms behind the anticolitis activity of miR168a. This study provided new evidence of the cross-kingdom regulatory effects of dietary miRNAs, suggesting the potential of the plant miRNA for the prevention and treatment of inflammatory bowel diseases.

The Microbial Perspective: A Systematic Literature Review on Hypertension and Gut Microbiota.

Understanding the causes of hypertension is important in order to prevent the disease. Gut microbiota (GM) seems to play an important role, but the detailed physiology remains elusive, with alpha diversity being the most studied indicator. This review aimed to systematically synthesize data on gut microbiota (alpha diversity) and hypertension. Databases, including MEDLINE/PubMed, Scopus, and EMBASE, and citations were systematically queried. We retrieved articles reporting the association between gut microbiota and hypertension. A valid critical appraisal tool was also used to investigate the quality of the included studies. Eighteen eligible studies met our inclusion criteria. In this report, we focused on the following indices of alpha diversity: Shannon, Chao1, Simpson, and Abundance-based Coverage Estimator (ACE) indices. Several studies observed a significantly lower Shannon index in hypertensive patients compared to the healthy control group. Nevertheless, no statistically significant difference was found for the Chao1, Simpson, and ACE indices between hypertensive patients and controls. A higher Firmicutes-to-Bacteroidetes ratio (F/B ratio) was consistently observed in hypertensive patients compared to healthy controls, indicating potential dysbiosis in the gut microbiota. Our systematic review indicates that hypertensive patients may exhibit an imbalance in gut microbiota, evidenced by decreased alpha diversity and an elevated F/B ratio. However, the absence of statistically significant differences in secondary diversity indices (Chao1, Simpson, and ACE) highlights the need for further research. Well-designed, large-scale studies are necessary to clarify these associations and explore the role of gut microbiota in hypertension development.

Association of gut microbiota imbalance with risk of postoperative infections in patients with left ventricular assist device

Abstract Background Infections are the most common complications following left ventricular assist device (LVAD) implantation and associated with adverse events. Gut microbial imbalance may predispose to mucosal colonization with pathogens, resulting in a risk of subsequent serious infections. However, it remains unclear whether gut microbiota imbalance is associated with postoperative infections in patients with LVAD. Purpose The aim of this study was to investigate whether gut microbiota imbalance was associated with postoperative infections in patients with LVAD. Methods We prospectively examined 22 consecutive LVAD patients who were admitted to a university hospital for routine check-ups and had stool cultures taken between March 2022 and December 2023. All patients had no signs of infection. The patients were divided into two groups according to positive (normal bacterial flora and other bacteria including Streptococcus viridans, Klebsiella, or Extended-spectrum β-lactamase Escherichia coli; n = 7) and negative (normal bacterial flora only; n = 15) for stool culture. The primary outcome was serious infection requiring hospitalisation treated with intravenous antimicrobial agents. Results Patients were predominantly male (68%) and the median age was 49 (interquartile range [IQR] 29-58) years. There were no significant differences in age, sex, primary aetiology of heart failure, type of LVAD devices, time on LVAD support, the history of infection, or antibiotics use within six months between the groups. During a median follow-up period of 316 days (IQR 242-559), the primary outcome occurred in seven patients (32%), including four hospitalisation for driveline infections, two pneumoniae and bacterial bloodstream infections, and one lung abscess and bacterial bloodstream infection. Kaplan–Meier analysis showed that the adverse events more frequently occurred in LVAD patients with positive for stool culture (P = 0.010) (Figure). A multivariable Cox regression analysis showed that positive for stool culture was independently associated with an increased subsequent risk of the primary outcome (hazard ratio 6.99, 95% confidence interval 1.17-41.7, P = 0.033), even after adjustments for age, male, body mass index, diabetes, INTERMACS profile, mechanical circulatory support, serum creatinine, serum albumin, and white blood cell count, which are known to be strong determinants of worse clinical outcomes in patients with LVAD. Conclusions In patients with LVAD, gut microbial imbalance was associated with subsequent serious infections. These findings suggest that the screening of stool culture might be useful for early identification of high-risk patients for infectious complication after LVAD implantation.

Associations between Gut Microbiota and Microbial Metabolites in Adjuvant- induced Arthritis Rats with Moist Heat Arthralgia Spasm Syndrome.

Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease. According to Traditional Chinese Medicine (TCM) syndromes theory, moist heat arthralgia spasm syndrome is the most prevalent syndrome of RA patients in the active period. However, the mechanism of alteration of gut microbiota in RA with moist heat arthralgia spasm syndrome has not been reported until now. This study focused on the alteration of gut microbiota in adjuvant-induced arthritis rats with moist heat arthralgia spasm syndrome, elaborated its regulation mechanism, and analyzed the associations between gut microbiota and microbial metabolites. The disease-syndrome combination rat model of RA with moist heat arthralgia spasm syndrome was constructed with Adjuvant-Induced Arthritis (AIA) under damp-heat stimulating. Enzyme-Linked Immunosorbent Assay (ELISA) was used to measure serum biochemical indicators. Damages of ankle joints were observed using hematoxylin and eosin (H&E). 16 small ribosomal subunit RNA (16S rRNA) gene sequencing was conducted to assess the gut microbiota composition and function on feces from rats. Alterations in fecal metabolites profiling were evaluated by fecal metabolomics through Liquid Chromatography-Mass Spectrometry (LC-MS) and Gas Chromatography-Mass Spectrometry (GC-MS). Pearson correlation analysis was performed to explore the associations of altered gut microbiota and microbial metabolites in Model rats. The imbalance of gut microbiota in Model rats was accompanied by metabolic disorders. Lactobacillus, Prevotellaceae_NK3B31_group, Allobaculum, Prevotellaceae_UCG_001, Alloprevotella, and Dubosiella were found to be dominant genera in Model rats. In total, 357 metabolites were significantly altered in Model rats and predominantly enriched into fatty acid degradation and glycerophospholipid metabolism. Pearson correlation analysis showed that TNF-α and IL-1β were associated with Prevotellaceae_Ga6A1_group and 3R-hydroxy-docosan-5S-olide, alpha-N-(3-hydroxy-14-methyl-pentadecanoyl)-ornithine, 17-methyl-trans-4,5- methylenenona-decanoic acid, Semiplenamide F. The key differential microbiota genera and differential microbial metabolites may become important targets for the treatment of RA and provide the theoretical basis for exploring the pathogenesis of RA.

Black Rice Extract Reduces Body Weight, Waist Circumference, Body Mass Index and Lipopolysaccharide in Obese Subjects: A Preliminary Study

BACKGROUND: The prevalence of obesity, or an excessive fat accumulation, is keep increasing. In obesity, inflammation can be induced by leaky gut due to the intestinal tight junction barrier dysfunction. Zonula occludens-1 (ZO-1) plays a role in developing intestinal tight junction barrier dysfunction and gut microbiota imbalance, thus promote the translocation of bacterial endotoxin characterized by lipopolysaccharide (LPS) into circulation. Black rice extract (BRE) has been known to have anti-inflammatory property. This study was conducted to investigate the effect of BRE on body weight (BW), waist circumference (WC), body mass index (BMI), ZO-1 and LPS of obese patients.METHODS: Twenty-three male subjects were divided into non-obese group (NOG), obese group (COG) and BRE-obese group (BOG). Subjects in BOG received a daily dose of 5.6 g/day BRE for 4 weeks. BW, WC and BMI, serum ZO-1 and LPS were measured before and after treatment.RESULTS: BRE was prepared successfully and free from microbial contamination. Treatment of BRE for 4 weeks reduce BW (95.40±5.78 vs. 94.59±6.00 kg, p=0.043), WC (109.25±3.55 vs. 107.50±3.46 cm, p=0.000) BMI (32.65±1.86 vs. 32.18±1.80, p=0.000) and LPS (222.27±38.63 vs. 131.63±9.70 ng/mL, p=0.020) of obese subjects. The pre-post ZO-1 levels in all groups were not significantly different (p>0.05).CONCLUSION: Treatment of 5.6 gr BRE daily for four weeks can reduce BW, WC, BMI and serum LPS, but not serum ZO-1 in obese patients. Therefore, BRE may reduce inflammation in obesity.KEYWORDS: black rice, obesity, BW, WC, BMI, LPS, ZO-1

Alterations of gut microbiome profiles as potential markers in patients developing acute coronary syndrome

Abstract Background Imbalanced gut microbiota or gut dysbiosis leads to systemic inflammation, one of key contributors to the development and progression of atherosclerosis. A recent study revealed the association of the gut microbiota and the severity of coronary artery lesions in patients with acute coronary syndrome (ACS). However, the gut microbiota profile in ACS patients in comparison with patients with high-risk cardiovascular disease (CVD) has not been thoroughly investigated. Purpose We aimed to compare the profiles of gut microbiome between patients with ACS and patients with high-risk CVD, as well as to determine the association between gut microbiota and CVD risk factors. Methods This cross-sectional study enrolled 24 stabilized ACS patients within 24 hrs of hospitalization and 59 outpatients in CVD clinics, as a control group. Echocardiography was done in those patients. Blood was collected for biochemical analysis, and fecal samples were collected for gut microbiome analysis via 16S RNA sequencing. Results The demographic data showed no significant differences between groups in CVD risk factors (age, levels of systolic and diastolic blood pressure, fasting glucose, high- and low-density cholesterol, and triglycerides). However, patients with ACS had greater cigarette use and alcohol consumption than the control group. For gut microbiome, both alpha and beta diversity levels of ACS group were significantly higher than those in a control group (Figure 1A-B). Differential abundance analysis by ANCOM-BC revealed significantly increased level of bacteria in the Atopobiaceae family in ACS patients, compared to controls (Figure 1C). Since Atopobiaceae was reported to be positively associated with percent atheroma volume (PAV), a marker of plaque deposit in the arteries, we found an increased number of Atopobiaceae which was positively associated with serum Troponin T level (Figure 1D), systemic inflammation (Figure 1E), and a trend to negatively correlated with LV ejection fraction. Conclusion Our findings suggested that alterations of gut microbiota occurred in ACS patients, and an increase in gut Atopobiaceae level could potentially be the predictive marker of the development of ACS in CVD patients.Figure 1

Exploring alterations of gut/blood microbes in addressing iron overload-induced gut dysbiosis and cognitive impairment in thalassemia patients

Iron overload causes cognitive impairment in thalassemia patients. The gut-brain axis plays an important role in cognitive function. However, the association between gut/blood microbiome, cognition, and iron burden in thalassemia patients has not been thoroughly investigated. We aimed to determine those associations in thalassemia patients with different blood-transfusion regimens. Sixty participants: healthy controls, transfusion-dependent thalassemia (TDT) patients, and non-transfusion-dependent (NTDT) patients, were recruited to evaluate iron overload, cognition, and gut/blood microbiome. TDT patients exhibited greater iron overload than NTDT patients. Most thalassemia patients developed gut dysbiosis, and approximately 25% of the patients developed minor cognitive impairment. Increased Fusobacteriota and Verrucomicrobiota with decreased Fibrobacterota were observed in both TDT and NTDT groups. TDT patients showed more abundant beneficial bacteria: Verrucomicrobia. Iron overload was correlated with cognitive impairment. Increased Butyricimonas and decreased Paraclostridium were associated with higher cognitive function. No trace of blood microbiota was observed. Differences in blood bacterial profiles of thalassemia patients and controls were insignificant. These findings suggest iron overload plays a role in the imbalance of gut microbiota and impaired cognitive function in thalassemia patients. Harnessing probiotic potential from those microbes could prevent the gut-brain disturbance in thalassemia patients.

Aging-induced dysbiosis worsens sepsis severity but is attenuated by probiotics in D-galactose-administered mice with cecal ligation and puncture model.

Despite the well-established effects of aging on brain function and gut dysbiosis (an imbalance in gut microbiota), the influence of aging on sepsis-associated encephalopathy (SAE) and the role of probiotics in this context remain less understood. C57BL/6J mice (8-week-old) were subcutaneously administered with 8 weeks of D-galactose (D-gal) or phosphate buffer solution (PBS) for aging and non-aging models, respectively, with or without 8 weeks of oral Lacticaseibacillus rhamnosus GG (LGG). Additionally, the impact of the condition media from LGG (LCM) was tested in macrophages (RAW 264.7 cells), microglia (BV-2 cells), and hippocampal cells (HT-22 cells). Fecal microbiome analysis demonstrated D-gal-induced dysbiosis (reduced Firmicutes and Desulfobacterota with increased Bacteroidota and Verrucomicrobiota), which LGG partially neutralized the dysbiosis. D-gal also worsens cecal ligation and puncture (CLP) sepsis severity when compared with PBS-CLP mice, as indicated by serum creatinine (Scr) and alanine transaminase (ALT), but not mortality, neurological characteristics (SHIRPA score), and serum cytokines (TNF-α and IL-6). Additionally, D-gal-induced aging was supported by fibrosis in the liver, kidney, and lung; however, CLP sepsis did not worsen fibrosis. Interestingly, LGG attenuated all parameters (mortality, Scr, ALT, SHIRPA, and cytokines) in non-aging sepsis (PBS-CLP) while improving all these parameters, except for mortality and serum IL-6, in aging sepsis (D-gal CLP). For the in vitro test using lipopolysaccharide (LPS) stimulation, LCM attenuated inflammation in some parameters on RAW264.7 cells but not BV-2 and HT-22 cells, implying a direct anti-inflammatory effect of LGG on macrophages, but not in cells from the brain. D-gal induced fecal dysbiosis and worsened sepsis severity as determined by Scr and ALT, and LGG could alleviate most of the selected parameters of sepsis, including SAE. However, the impact of LGG on SAE was not a direct delivery of beneficial molecules from the gut to the brain but partly due to the attenuation of systemic inflammation through the modulation of macrophages.

Serum neurofilament light chain in response to probiotics in bi-center, double-blind, randomized, placebo-controlled clinical trial (CleverAge Biota).

Neurodegenerative disorders affecting the brain and spinal cord are caused by a large number of factors. More recently, imbalances in gut microbiota are found to be one factor linked directly to neurological dysfunction. Probiotics prevent cognitive decline. For the first time, the effect of probiotics was assessed by monitoring the concentrations of the neurodegeneration biomarker neurofilament light chains (NfL) in a well-defined group of community-dwelling individuals. The aim of this study was to determine whether administration of our new probiotics could reduce NfL concentrations. The serum NfL concentrations were measured in total of 190 serum samples of 85 older community-dwelling individuals. The participants were randomly divided into two groups: the PROPLA group and the PLAPRO group. Individuals in the PROPLA group started with a three-month use of probiotics and continued with a three-month use of placebo while the order was reversed in the PLAPRO group. The participants underwent detailed examinations at three time points: at baseline, in three and six months. The serum NfL concentrations were determined using ultrasensitive single-molecule array (SIMOA) assay. Longitudinal comparisons of NfL concentrations between samplings at different time points in the PROPLA and PLAPRO groups showed no statistically significant differences. Baseline NfL concentrations at the beginning of the study and in the succeeding samplings were not significantly different for the two groups in cross-sectional comparisons. Serum NfL concentrations were not influenced by the three-month use of probiotics.

Harnessing Prebiotics to Improve Type 2 Diabetes Outcomes.

The gut microbiota, a complex ecosystem of microorganisms in the human gastrointestinal tract (GI), plays a crucial role in maintaining metabolic health and influencing disease susceptibility. Dysbiosis, or an imbalance in gut microbiota, has been linked to the development of type 2 diabetes mellitus (T2DM) through mechanisms such as reduced glucose tolerance and increased insulin resistance. A balanced gut microbiota, or eubiosis, is associated with improved glucose metabolism and insulin sensitivity, potentially reducing the risk of diabetes-related complications. Various strategies, including the use of prebiotics like inulin, fructooligosaccharides, galactooligosaccharides, resistant starch, pectic oligosaccharides, polyphenols, β-glucan, and Dendrobium officinale have been shown to improve gut microbial composition and support glycemic control in T2DM patients. These prebiotics can directly impact blood sugar levels while promoting the growth of beneficial bacteria, thus enhancing glycemic control. Studies have shown that T2DM patients often exhibit a decrease in beneficial butyrate-producing bacteria, like Roseburia and Faecalibacterium, and an increase in harmful bacteria, such as Escherichia and Prevotella. This review aims to explore the effects of different prebiotics on T2DM, their impact on gut microbiota composition, and the potential for personalized dietary interventions to optimize diabetes management and improve overall health outcomes.

Unveiling the Role of Gut Microbiota and Metabolites in Autoimmune Thyroid Diseases: Emerging Perspectives.

Autoimmune thyroid diseases (AITDs) are among the most prevalent organ-specific autoimmune disorders, with thyroid hormones playing a pivotal role in the gastrointestinal system's structure and function. Emerging evidence suggests a link between AITDs and the gut microbiome, which is a diverse community of organisms that are essential for digestion, absorption, intestinal homeostasis, and immune defense. Recent studies using 16S rRNA and metagenomic sequencing of fecal samples from AITD patients have revealed a significant correlation between a gut microbiota imbalance and the severity of AITDs. Progress in animal models of autoimmune diseases has shown that intervention in the gut microbiota can significantly alter the disease severity. The gut microbiota influences T cell subgroup differentiation and modulates the pathological immune response to AITDs through mechanisms involving short-chain fatty acids (SCFAs), lipopolysaccharides (LPSs), and mucosal immunity. Conversely, thyroid hormones also influence gut function and microbiota composition. Thus, there is a bidirectional relationship between the thyroid and the gut ecosystem. This review explores the pathogenic mechanisms of the gut microbiota and its metabolites in AITDs, characterizes the gut microbiota in Graves' disease (GD) and Hashimoto's thyroiditis (HT), and examines the interactions between the gut microbiota, thyroid hormones, T cell differentiation, and trace elements. The review aims to enhance understanding of the gut microbiota-thyroid axis and proposes novel approaches to mitigate AITD severity through gut microbiota modulation.

Lactobacillus rhamnosus ameliorates experimental autoimmune neuritis via modulation of gut microbiota and metabolites

BackgroundGuillain-Barre syndrome (GBS), an autoimmune disease of the peripheral nervous system, is hallmarked by demyelination and immune cellular infiltration. Experimental autoimmune neuritis (EAN), considered a GBS prototype model, has been studied for its potential therapeutic benefits from lactobacilli. This study evaluated the protective role of Lactobacillus rhamnosus GG (GG) for treatment in EAN. T cell ratio, inflammation factors, sciatic nerve pathology, intestinal permeability, and gut inflammation were assessed on day 19 post-immunization to evaluate GG's effect on EAN. Fecal metabolomics and 16s rRNA microbiome analysis were conducted to elucidate its mechanism. ResultsGG dynamically balanced CD4+/CD8+T cell ratio, reduced serum IL-1β and TNF-α expression, improved sciatic nerve demyelination and inflammation, and enhanced neurological scores during peak disease period. Intestinal mucosal damage was evident in EAN rats, with downregulated Occludin and ZO-1 and upregulated IL-1β, TNF-α, and Reg3γ. GG treatment restored intestinal mucosal integrity, upregulated Occludin and ZO-1, and downregulated IL-1, TNF-α, and Reg3γ. GG partially rectified the gut microbiota and metabolite imbalance in EAN rats. ConclusionGG mitigates EAN through immune response modulation and inflammation reduction via the gut microbiota and metabolites.

From dysbiosis to disease: Tracing gut microbiota's role in neonatal sepsis

IntroductionNeonatal sepsis remains a critical health issue, contributing significantly to morbidity and mortality among preterm infants. Dysbiosis, an imbalance in gut microbiota, is increasingly recognized as a key factor influencing the susceptibility to sepsis. This study aims to elucidate these associations by tracing gut microbiota development in preterm neonates. Methodology: A prospective cohort study was conducted at a tertiary care hospital in Karnataka, India, involving 182 preterm neonates (gestational age <37 weeks, birth weight <1500 g) from January 2021 to September 2023. Two cohorts were defined: Cohort 1 (Healthy neonates) and Cohort 2 (Neonates with sepsis). Stool samples were collected on day 4 and day 14 for microbiological analysis. Conventional culture techniques were used to identify bacterial isolates. ResultsThe study included 182 neonates, equally divided between two cohorts. On Day 4, Cohort 1 had 45 % E. coli and 44 % Klebsiella pneumoniae, which decreased to 40.7 % and 40.7 % by Day 14, respectively. Conversely, Bifidobacterium spp. increased from 30.8 % to 52.7 %. Cohort 2 exhibited higher persistence of pathogenic bacteria, with Klebsiella pneumoniae increasing from 70.3 % to 74.7 % and E. coli from 38.5 % to 51.6 %. Mode of delivery significantly influenced gut flora, with NVD linked to higher beneficial bacteria prevalence (Enterococcus faecalis and Bifidobacterium spp.). ConclusionThe study highlights significant differences in gut microbial patterns between healthy and sepsis neonates, emphasizing the role of initial gut colonization in neonatal health outcomes. Factors such as delivery mode and prenatal antibiotic exposure significantly impact gut microbiota composition, influencing infection susceptibility.

Chinese herbal formula in the treatment of metabolic dysfunction-associated steatotic liver disease: current evidence and practice.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease, continues to rise with rapid economic development and poses significant challenges to human health. No effective drugs are clinically approved. MASLD is regarded as a multifaceted pathological process encompassing aberrant lipid metabolism, insulin resistance, inflammation, gut microbiota imbalance, apoptosis, fibrosis, and cirrhosis. In recent decades, herbal medicines have gained increasing attention as potential therapeutic agents for the prevention and treatment of MASLD, due to their good tolerance, high efficacy, and low toxicity. In this review, we summarize the pathological mechanisms of MASLD; emphasis is placed on the anti-MASLD mechanisms of Chinese herbal formula (CHF), especially their effects on improving lipid metabolism, inflammation, intestinal flora, and fibrosis. Our goal is to better understand the pharmacological mechanisms of CHF to inform research on the development of new drugs for the treatment of MASLD.

Integrated Small Intestine Microbiota and Serum Metabolomics Reveal the Potential Mechanisms of Wine Steaming in Alleviating Rhubarb-Induced Diarrhea.

Long-term use of rhubarb (RH) commonly leads to diarrhea, which can be alleviated by steaming with wine. However, the specific mechanism by which wine steaming alleviates RH-induced diarrhea remains unknown. This study aims to reveal the underlying mechanisms of wine steaming in alleviating RH-induced diarrhea by examining small intestinal flora and serum metabolomics. Major anthraquinone and anthrone components were detected using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Eighty-four ICR mice were randomly divided into control, RH, and RH steamed with wine (PRH) groups and were administered RH and PRH (1, 4, and 8 g/kg, i.g). for 14 consecutive days. Histopathological analysis was performed using hematoxylin-eosin staining. Levels of inflammatory factors and tight junction proteins, zonula occludens-1 (ZO-1) and occludin, in the small intestine were measured. The small intestine content was analyzed using 16S rRNA sequencing, and UPLC-MS was used to analyze endogenous metabolites. Levels of major anthraquinone and anthrone components decreased in PRH. Both RH and PRH groups showed varying degrees of loose stools and increased fecal water rates; the RH group exhibited more severe effects. Compared with the control group, RH caused small intestine injuries, increased levels of inflammatory cytokines, downregulated the expression of ZO-1 and occludin, and induced gut microbiota (GM) imbalance. The relative abundance of Lactobacillus decreased, while the relative abundance of Shigella and Streptococcus increased. However, PRH had a milder impact than RH. The glycerophospholipid metabolic pathway was involved in this effect. The levels of inflammatory cytokines and potential metabolites (sn-glycero-3-phosphoethanolamine) were positively correlated with Streptococcus infection, while the levels of ZO-1 and occludin were negatively correlated with Streptococcus infection. GM imbalance and abnormal glycerophospholipid metabolism contributed to impaired intestinal barrier function and inflammatory factor release, which may underlie RH-induced diarrhea, though PRH had a weaker effect. PRH alleviated RH-induced diarrhea by recovering GM balance, reducing ZO-1 and occludin expression, and decreasing the release of inflammatory factors. This mechanism may be linked to the reduced anthraquinone content. This study is the first to explore the mechanism of wine steaming in alleviating RH-induced diarrhea through small intestinal flora and serum metabolomics. It provides data to support the broader clinical use of RH and its safer application.

Effects of Ferulic Acid on Lipopolysaccharide-Induced Oxidative Stress and Gut Microbiota Imbalance in Linwu Ducks.

Oxidative stress is a major factor that limits the development of the poultry industry. Ferulic acid (FA) has an antioxidant effect in birds, but the mechanism is not fully understood. In this study, we stimulated oxidative stress in 28-day-old female Linwu ducks by lipopolysaccharide (LPS) and fed them a diet supplemented with FA for 28 days. Results showed that FA alleviated LPS-induced growth performance regression, oxidative stress, and microbiota imbalance in ducks. An integrated metagenomics and metabolomics analysis revealed that s_Blautia_obeum, s_Faecalibacterium_prausnitzii, s_gemmiger_formicilis, and s_Ruminococcaceae_bacterium could be the biomarkers in the antioxidant effect of FA, which interacted with dihydro-3-coumaric acid, L-phenylalanine, and 13(S)-HODE, and regulated the phenylalanine metabolism and PPAR signaling pathway. This study revealed the mechanism of the antioxidant effect of FA, which provided evidence of applying FA as a new antioxidant in commercial duck production.

A New Combination of Bifidobacterium bifidum and Lactococcus lactis Strains with Synergistic Effects Alleviates Colitis-Associated Colorectal Cancer.

Chronic inflammation is a factor in the development of cancer, and probiotics play a role in preventing or treating inflammation as an adjuvant therapy. To investigate potential probiotics for the prevention of colitis-associated colorectal cancer (CAC), Bifidobacterium bifidum H3-R2 and Lactococcus lactis KLDS4.0325 were used to examine the effects on colon cancer cells and in an inflammation-related cancer animal model. The results revealed that B. bifidum H3-R2 in combination with L. lactis KLDS4.0325 caused apoptosis in colon cancer cells by increasing caspase-3 and caspase-9 protein levels, enhancing Bax expression, and lowering Bcl-2 expression. In addition, the combination of the two strains relieved the tissue damage; reduced proinflammatory cytokines, myeloperoxidase (MPO) activity, and hypoxia-inducible factor 1-alpha (HIF-1α) level; upregulated anti-inflammatory cytokines; increased colonic tight junction protein expression; regulated intestinal homeostasis by inhibiting NLRP3 inflammasome signaling pathway; and improved the imbalance of gut microbiota in animal models. Moreover, the combination of the two strains had a greater preventive impact than each strain alone. These findings are supportive of clinical studies and product development of multi-strain probiotic preparations for diseases associated with colitis.