Alcohol‐induced liver injury implicates inflammation and oxidative stress as important mediators. Despite rigorous research, there is still no Food and Drug Administration (FDA) approved therapies for any stage of alcoholic liver disease (ALD). Interestingly, metformin (Met) and several probiotic strains possess the potential of inhibiting alcoholic liver injury. Therefore, we investigated the effectiveness of combination therapy using a mixture of eight strains of lactic acid‐producing bacteria, commercialized as Visbiome® (V) and Met in preventing the ethanol‐induced hepatic injury using in vitro and in vivo models. Human HepG2 cells and male Wistar rats were exposed to ethanol and simultaneously treated with probiotic V or Met alone as well as in combination. Endoplasmic reticulum (ER) stress markers, inflammatory markers, lipid metabolism, reactive oxygen species (ROS) production, and oxidative stress were evaluated, using qRT‐PCR, Oil red O staining, fluorimetry, and HPLC. In vitro, probiotic V and Met in combination prevented ethanol‐induced cellular injury, ER stress, oxidative stress, and regulated lipid metabolism as well as inflammatory response in HepG2 cells. Probiotic V and Met also promoted macrophage polarization towards the M2 phenotype in ethanol‐exposed RAW 264.7 macrophage cells. In vivo, combined administration of probiotic V and Met ameliorated the histopathological changes, inflammatory response, hepatic markers (liver enzymes), and lipid metabolism induced by ethanol. It also improved the antioxidant markers (HO‐1 and Nrf‐2), as seen by their protein levels in both HepG2 cells as well as liver tissue using ELISA. Hence, probiotic V may act, in addition to the Met, as an effective preventive treatment against ethanol‐induced hepatic injury.

Obesity is a global health concern, necessitating effective weight-loss interventions. This study aimed to compare the efficacy and safety of semaglutide, a pharmacotherapeutic option, with bariatric surgery, a commonly utilized surgical intervention, for weight reduction. A systematic review of clinical trials, including the STEP (Semaglutide Treatment Effect in People) trials, sustain trials, pioneer trials, and the STAMPEDE (Surgical Treatment and Medications Potentially Eradicate Diabetes Efficiently) trial, was conducted to evaluate the outcomes of these interventions. The analysis of the clinical trials revealed that semaglutide demonstrated significant weight reduction in participants. However, adverse effects such as gastrointestinal (GI) disturbances, increased pulse rate, and rare cases of thyroid cancer were observed. Long-term effects showed partial weight regain and a return of certain cardiometabolic variables to baseline levels after semaglutide withdrawal. Comparatively, bariatric surgery, as demonstrated in the Longitudinal Assessment of Bariatric Surgery (LABS) consortium and supported by the STAMPEDE trial, exhibited higher efficacy in weight reduction and the management of obesity-induced complications such as diabetes. The STAMPEDE trial demonstrated that bariatric surgery, specifically Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), led to a significantly higher percentage of patients achieving desired diabetes treatment targets compared to medical therapy alone. While bariatric surgery showed superior efficacy, it also carried a higher risk of complications. In contrast, semaglutide presented a noninvasive alternative with significant weight reduction and lower incidences of adverse effects. In conclusion, this study highlights that bariatric surgery, such as Roux-en-Y gastric bypass and sleeve gastrectomy, remains a highly effective intervention for weight loss and management of obesity-induced complications. However, semaglutide represents a valuable noninvasive alternative, offering significant weight reduction and lower risks of adverse effects. The choice between these interventions should be based on individual patient characteristics and a comprehensive assessment of the risk-benefit profile.

Alcoholic liver disease (ALD) alters gut microbiota and tight junctions, causing bacterial components to enter the portal vein and induce oxidative stress-induced inflammation in the liver. Only corticosteroids and liver transplants are treatment options for severe alcoholic hepatitis. ALD’s pathophysiology is unknown. However, acetaldehyde’s toxic effects cause oxidative stress and intestinal permeability. This study investigates the influence of a synbiotic (a combination of aged garlic extract (AGE) and Lactobacillus rhamnosus MTCC1423) on colonic oxidative stress and inflammation in ALD male Wistar rats and Caco2 cells. MDA measurement by HPLC in CaCo2 cells, blood serum, and colon tissue demonstrated that synbiotic treatment in the ALD model reduces oxidative stress. Further, fecal high-throughput 16S rRNA gene sequencing revealed the microbiome’s shift towards Firmicutes in the synbiotic group compared to ethanol. In addition, DCFDA labeling and H/E staining demonstrate that the synbiotic is beneficial in inhibiting the development of ALD. In the colon, the synbiotic reduces the activation of CYP2E1 and the inflammatory markers TNF-a and IL-6 while elevating the mRNA expression of ZO-1, occludin, and IL-10. Synbiotics colonize Lactobacillus to restore barrier function and microbiota and reduce colon oxidative stress. Thus, a synbiotic combination can be used in ALD treatment.

Consumption of alcohol (ethanol) in various forms has been an integral part of human civilization. Since ages, it also has been an important cause of death and health impairment across the globe. Ethanol-mediated liver injury, known as alcoholic liver disease (ALD), is caused by surplus intake of alcohol. Several studies have proposed the different pathways that may be lead to ALD. One of the factors that may affect the cytochrome P450 (CYP2E1) metabolic pathway is gut dysbiosis. The gut microbiota produces various compounds that play an important role in regulating healthy functions of distal organs such as the adipose tissue and liver. Dysbiosis causes bacteremia, hepatic encephalopathy, and increased intestinal permeability. Recent clinical studies have found better understanding of the gut and liver axis. Another factor that may affect the ALD pathway is dysfunction of adipose tissue metabolism. Moreover, dysfunction of adipose tissue leads to ectopic fat deposition within the liver and disturbs lipid metabolism by increasing lipolysis/decreasing lipogenesis and impaired glucose tolerance of adipose tissue which leads to ectopic fat deposition within the liver. Adipokine secretion of resistin, leptin, and adiponectin is adversely modified upon prolonged alcohol consumption. In the combination of these two factors, a proinflammatory state is developed within the patient leading to the progression of ALD. Thus, the therapeutic approach for treatments and prevention for liver cirrhosis patients must be focused on the gut-liver-adipose tissue network modification with the use of probiotics, synbiotics, and prebiotics. This review is aimed at the effect of ethanol on gut and adipose tissue in both rodent and human alcoholic models.

Increased blood glucose in diabetic individuals results in the formation of advanced glycation end products (AGEs), causing various adverse effects on kidney cells, thereby leading to diabetic nephropathy (DN). In this study, the antiglycative potential of Swertiamarin (SM) isolated from the methanolic extract of E. littorale was explored. The effect of SM on protein glycation was studied by incubating bovine serum albumin with fructose at 60 °C in the presence and absence of different concentrations of swertiamarin for 24 h. For comparative analysis, metformin was also used at similar concentrations as SM. Further, to understand the role of SM in preventing DN, in vitro studies using NRK-52E cells were done by treating cells with methylglyoxal (MG) in the presence and absence of SM. SM showed better antiglycative potential as compared to metformin. In addition, SM could prevent the MG mediated pathogenesis in DN by reducing levels of argpyrimidine, oxidative stress and epithelial mesenchymal transition in kidney cells. SM also downregulated the expression of interleukin-6, tumor necrosis factor-α and interleukin-1β. This study, for the first time, reports the antiglycative potential of SM and also provides novel insights into the molecular mechanisms by which SM prevents toxicity of MG on rat kidney cells.

Ethanol depletes intestinal integrity and promotes gut dysbiosis. Studies have suggested the individual role of probiotics and metformin Met in protecting intestinal barrier function from injuries induced by ethanol. The objective of the current study is to investigate the potential mechanism by which coadministration of probiotic Visbiome® (V) and Met blocks the ethanol‐induced intestinal barrier dysfunction/gut leakiness utilizing Caco‐2 monolayers, a rat model with chronic ethanol injury, and in silico docking interaction models. In Caco‐2 monolayers, exposure to ethanol significantly disrupted tight junction (TJ) localization, elevated monolayer permeability, and oxidative stress compared with controls. However, cotreatment with probiotic V and Met largely ameliorated the ethanol‐induced mucosal barrier dysfunction, TJ disruption, and gut oxidative stress compared with ethanol‐exposed monolayers and individual treatment of either agent. Rats fed with ethanol‐containing Lieber‐DeCarli liquid diet showed decreased expression of TJ proteins, and increased intestinal barrier injury resulting in pro‐inflammatory response and oxidative stress in the colon. We found that co‐administration of probiotic V and Met improved the expression of intestinal TJ proteins (ZO‐1 and occludin) and upregulated the anti‐inflammatory response, leading to reduced ER stress. Moreover, co‐administration of probiotic V and Met inhibited the CYP2E1 and NOX gene expression, and increase the translocation of Nrf‐2 as well as anti‐oxidative genes (SOD, catalase, Gpx, and HO‐1), leading to reduced colonic ROS content and malondialdehyde levels. The combined treatment of probiotic V and Met also improved their binding affinities towards HO‐1, Nrf‐2, SLC5A8, and GPR109A, which could be attributed to their synergistic effect. Our findings based on in-vitro, in-vivo, and in-silico analyses suggest that the combination of probiotic V and Met potentially acts in synergism, attributable to their property of inhibition of inflammation and oxidative stress against ethanol‐induced intestinal barrier injury.