Hepatotoxicity is one of the biggest health challenges, particularly in the context of liver diseases, often aggravated by gut microbiota dysbiosis. The gut-liver axis has been regarded as a key idea in liver health. It indicates that changes in gut flora caused by various hepatotoxicants, including alcoholism, acetaminophen, carbon tetrachloride, and thioacetamide, can affect the balance of the gut's microflora, which may lead to increased dysbiosis and intestinal permeability. As a result, bacterial endotoxins would eventually enter the bloodstream and liver, causing hepatotoxicity and inducing inflammatory reactions. Many treatments, including liver transplantation and modern drugs, can be used to address these issues. However, because of the many side effects of these approaches, scientists and medical experts are still hoping for a therapeutic approach with fewer side effects and more positive results. Thus, probiotics have become well-known as an adjunctive strategy for managing, preventing, or reducing hepatotoxicity in treating liver injury. By altering the gut microbiota, probiotics offer a secure, non-invasive, and economical way to improve liver health in the treatment of hepatotoxicity. Through various mechanisms such as regulation of gut microbiota, reduction of pathogenic overgrowth, suppression of inflammatory mediators, modification of hepatic lipid metabolism, improvement in the performance of the epithelial barrier of the gut, antioxidative effects, and modulation of mucosal immunity, probiotics play their role in the treatment and prevention of hepatotoxicity. This review highlights the mechanistic effects of probiotics in environmental toxicants-induced hepatotoxicity and current findings on this therapeutic approach's experimental and clinical trials.

This study aimed to develop a selenium nanoparticles (SeNPs)-enriched probiotic strain with potential anti-hangover effects. Pediococcus acidilactici JW-015 was screened for its high tolerance to inorganic selenium (up to 80 mM sodium selenite) and efficient synthesis of SeNPs, achieving a selenium accumulation concentration of 6974 ± 90.71 μg/g, with SeNPs accounting for 86.54% ± 2.48%. Safety and probiotic properties were evaluated, confirming that JW-015 is a safe probiotic strain and that selenium enrichment enhanced its probiotic properties. Furthermore, JW-015 demonstrated significant anti-hangover efficacy, with selenium enrichment improving the oxidative stress capacity, alcohol tolerance, alcohol degradation ability, and relevant enzyme activities (ADH and ALDH) of the strain. This study provides a promising bio-carrier for SeNPs transformation and expands the applications of selenium-enriched LAB.

The Gut Microbiome-Liver-Brain Axis is a relatively novel construct with promising potential to enhance our understanding of Alcohol Use Disorder (AUD), and its therapeutic approaches. Significant alterations in the gut microbiome occur in AUD even before any other systemic signs or symptoms manifest. Prolonged and inappropriate alcohol consumption, by affecting the gut microbiota and gut mucosa permeability, is thought to contribute to the development of behavioral and cognitive impairments, leading to Alcohol-Related Liver Disorders and potentially progressing into alcoholic cirrhosis, which is often associated with severe cognitive impairment related to neurodegeneration, such as hepatic encephalopathy and alcoholic dementia. The critical role of the gut microbiota is further supported by the efficacy of FDA-approved treatments for hepatic encephalopathy in alcoholic cirrhosis (i.e., lactulose and rifaximin). To stimulate new research, we hypothesize that interactions between a maladaptive stress response and a constitutional predisposition to neurodegeneration underlie the progression of AUD to conditions of Alcohol-Related Clinical Concerns with severe cognitive impairment, which represent a significant and costly burden to society. Early identification of AUD individuals at risk for developing these conditions could help to prioritize integrated therapeutic interventions targeting different substrates of the Gut Microbiome-Liver-Brain axis. Specifically, addiction medications, microbiome modulators, stress-reducing interventions, and, possibly soon, novel agents that reduce hepatic steatosis/fibrosis will be discussed in the context of digitally supported integrated therapeutic approaches. The explicit goal of this AUD treatment performed on the early stage of the disorder would be to reduce the transition from AUD to those conditions of Alcohol-Related Common Clinical Concerns associated with severe cognitive impairment, a strategy recommended for most neurological neurodegenerative disorders.

Alcohol abuse-triggered alcohol-related liver disease (ALD) has become as a global public health concern that substantially affects the well-being and clinical status of patients. Although modern medicine provides various treatments for ALD, their effectiveness is limited and can lead to adverse side effects. Probiotics have been employed to prevent, alleviate, and even treat ALD, with promising results. However, few comprehensive reviews are available on how they mitigate ALD by targeting the gut-liver axis. This review systematically clarifies the specific mediators of the gut-liver axis in healthy states. It also describes the alterations observed in ALD. Furthermore, this review thoroughly summarizes the underlying mechanisms through which probiotics act on the gut-liver axis to relieve ALD. It also discusses the current status and challenges faced in clinical research applications. Finally, we discuss the challenges and future prospects of using probiotics to treat ALD. This review improves our understanding of ALD and supports the development and application of probiotics that target the gut-liver axis for therapeutic use.

Studies have shown that improving the intestinal flora can alleviate the progression of liver fibrosis. Cordycepin has shown potential anti-inflammatory and anti-fibrosis effects. In this study, we aimed to investigate the effects of cordycepin on liver fibrosis and how it affects the intestinal flora composition to determine a potentially effective therapeutic approach for liver fibrosis.

C57BL/6 mice were fed a special diet containing 3,5-diethoxycarbonyl-1,4-dihydroxylidine (DDC) to induce liver fibrosis. The histopathological changes in liver tissue and intestinal mucosa were determining via immunohistochemical staining. Serum transaminase levels were determined using biochemical test kits. Faecalibaculum samples were sequenced via 16S rRNA sequencing.

Cordycepin reduced DDC-induced liver collagen deposition, improved serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and reduced the levels of endothelial dysfunction markers vascular cell adhesion molecule 1 (VCAM) and thrombomodulin (TM). Our analysis of the intestinal flora composition showed that Dubosiella, Faecalibaculum, and Bifidobacterium were significantly increased in the cordycepin-treated group (P < 0.05). The Dubosiella level was significantly negatively correlated with TM and VCAM levels, and serum levels of ALT and AST (P < 0.05). After treatment with cordycepin, the microvilli length in the intestinal mucosa, the density of goblet cells, and the expressions of occludin and zonula occludens protein 1 (ZO-1) were significantly increased (P < 0.05).

We discovered that cordycepin improves liver fibrosis in vivo. We found that Dubosiella levels were considerably increased in the cordycepin-treated group and were significantly negatively correlated with liver sinusoidal endothelial damage.

Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are two major chronic liver diseases worldwide. The triggers for fatty liver can be derived from external sources such as adipose tissue, the gut, personal diet, and genetics, or internal sources, including immune cell responses, lipotoxicity, hepatocyte death, mitochondrial dysfunction, and extracellular vesicles. However, their pathogenesis varies to some extent. This review summarizes various immune mechanisms and therapeutic targets associated with these two types of fatty liver disease. It describes the gut-liver axis and adipose tissue-liver crosstalk, as well as the roles of different immune cells (both innate and adaptive immune cells) in fatty liver disease. Additionally, mitochondrial dysfunction, extracellular vesicles, microRNAs (miRNAs), and gastrointestinal hormones are also related to the pathogenesis of fatty liver. Understanding the pathogenesis of fatty liver and corresponding therapeutic strategies provides a new perspective for developing novel treatments for fatty liver disease.

Incidence of a number of liver diseases has increased. Gut microbiota serves a role in the pathogenesis of hepatitis, cirrhosis and liver cancer. Gut microbiota is considered 'a new virtual metabolic organ'. The interaction between the gut microbiota and liver is termed the gut‑liver axis. The gut‑liver axis provides a novel research direction for mechanism of liver disease development. The present review discusses the role of the gut‑liver axis and how this can be targeted by novel treatments for common liver diseases.

Substance use disorders (SUD) remain a major public health concern in which individuals are unable to control their use of substances despite significant harm and negative consequences. Drugs of abuse dysregulate major brain and behavioral functions. Glial cells, primarily microglia and astrocytes, play a crucial role in these drug-induced molecular and behavioral changes. This review explores preclinical and clinical studies of how neuroglia and their associated neuroinflammatory responses contribute to SUD and reward-related properties. We evaluate preclinical and clinical evidence for targeting neuroglia as therapeutic interventions. In addition, we evaluate the literature on the gut microbiome and its role in SUD. Clinical treatments are most effective for reducing drug cravings, and some have yielded promising results in other measures of drug use. N-Acetylcysteine, through modulation of cysteine-glutamate antiporter of glial cells, shows encouraging results across a variety of drug classes. Neuroglia and gut microbiome interactions are important factors to consider with regard to SUD and could lead to novel therapeutic avenues. Age- and sex-dependent properties of neuroglia, gut microbiome, and drug use behaviors are important areas in need of further investigation.

The global incidence and mortality rates of alcohol-related liver disease are on the rise, reflecting a growing health concern worldwide. Alcohol-related liver disease develops due to a complex interplay of multiple reasons, including oxidative stress generated during the metabolism of ethanol, immune response activated by immunogenic substances, and subsequent inflammatory processes. Recent research highlights the gut microbiota's significant role in the progression of alcohol-related liver disease. In patients with alcohol-related liver disease, the relative abundance of pathogenic bacteria, including Enterococcus faecalis, increases and is positively correlated with the level of severity exhibited by alcohol-related liver disease. Supplement probiotics like Lactobacillus, as well as Bifidobacterium, have been found to alleviate alcohol-related liver disease. The gut microbiota is speculated to trigger specific signaling pathways, influence metabolite profiles, and modulate immune responses in the gut and liver. This research aimed to investigate the role of gut microorganisms in the onset and advancement of alcohol-related liver disease, as well as to uncover the underlying mechanisms by which the gut microbiota may contribute to its development. This review outlines current treatments for reversing gut dysbiosis, including probiotics, fecal microbiota transplantation, and targeted phage therapy. Particularly, targeted therapy will be a vital aspect of future alcohol-related liver disease treatment. It is to be hoped that this article will prove beneficial for the treatment of alcohol-related liver disease.

Various types of liver or hepatic diseases cause the death of about 2 million people worldwide every year, of which 1 million die from the complications of cirrhosis and another million from hepatocellular carcinoma and viral hepatitis. Currently, the second most common solid organ transplant is the liver, and the current rate represents less than 10% of global transplant requests. Hence, finding new approaches to treat and prevent liver diseases is essential. In liver diseases, the interaction between the liver, gut, and immune system is crucial, and probiotics positively affect the human microbiota. Probiotics are a non-toxic and biosafe alternative to synthetic chemical compounds. Health promotion by lowering cholesterol levels, stimulating host immunity, the natural gut microbiota, and other functions are some of the activities of probiotics, and their metabolites, including bacteriocins, can exert antimicrobial effects against a broad range of pathogenic bacteria. The present review discusses the available data on the results of preclinical and clinical studies on the effects of probiotic administration on different types of liver diseases.

Probiotic sour beer (PRO) fermented with Lacticaseibacillus paracasei Lpc-37 is a novel beverage option, which may potentially offer health benefits. In this study, the effects of PRO are evaluated on the inflammatory, immunity, lipid profile, and gut microbiome of consumers in a 5-week, participant-blinded, randomized-controlled within-subject crossover study. Twenty-one healthy male participants consumed 330 mL of PRO and normal sour beer (CON) daily for 2 weeks each with a 1 week of washout. Stool and blood samples were collected before and after each intervention. Significant increases for Proteobacteria and Bacteroides and a significant decrease in Dialister (p < 0.05) were observed in the CON group, while gut microbiome populations remained relatively stable in the PRO group. A significant increase was also found in HDL-cholesterol after PRO (p < 0.05), while no significant differences were observed in inflammatory and immunity profiles. Further research is warranted to explore its HDL-cholesterol increasing potential.

Alcohol-related liver disease (ALD) encompasses a spectrum of hepatic disorders resulting from alcohol abuse, which constitutes the predominant etiology of morbidity and mortality associated with hepatic pathologies globally. Excessive alcohol consumption disrupts the integrity of the intestinal barrier and perturbs the balance of gut microbiota, thereby facilitating the progression of ALD. Ellagic acid (EA) has been extensively reported to be an effective intervention for alleviating liver symptoms. However, the target molecules of EA in improving ALD and its underlying mechanism remain elusive. First, our study indicates that EA ameliorated ALD through the hepatic circadian rhythm signaling by up-regulating neuronal PAS domain protein 2 (NPAS2). Furthermore, analysis of the intestinal microbiome showed that EA significantly enhanced the abundance of beneficial bacteria, which was positively correlated with NPAS2 expression and negatively correlated with liver injury. Finally, antibiotic treatment and fecal microbiota transplantation (FMT) experiments established a causal relationship between the reshaped microbiota and NPAS2 in the amelioration of ALD. In summary, our study demonstrates novel evidence that EA attenuated ALD by modulating the hepatic circadian rhythm signaling pathway via the gut microbiota-NPAS2 axis, providing valuable insights for EA and microbiome-targeted interventions against ALD.

Disruption of gut microbiota is closely related to the progression of alcoholic liver disease (ALD). This study aimed to explore the therapeutic effect of fecal microbiota transplantation (FMT) in ALD rats using a combination of microbiological and metabolomic techniques.

Three liver injury rat models were constructed using alcohol, CCL4, and alcohol combined with CCL4, and administered an FMT treatment comprising the fecal microbiota of healthy rats via the gastric route for 12 consecutive weeks. We measured the therapeutic effect of FMT treatment on liver inflammation, intestinal mucosal barrier, and bacterial translocation in ALD rats using 16S rRNA and UPLC-Q/TOF-MS technology to detect the effects of FMT on the intestinal microbiota and metabolic patterns of ALD rats.

FMT treatment effectively improved liver function, prolonged survival time, improved the intestinal mucosal barrier, reduced bacterial translocation, alleviated liver inflammation, and delayed the progression of liver fibrosis in three types of liver injury models. The microbiome and metabolomic results showed that FMT can effectively improve gut microbiota disorder in ALD rats and improve metabolic patterns by regulating metabolic pathways such as the arachidonic acid and retinol pathways.

FMT treatment could reverse alcohol induced liver injury by improving gut microbiota and metabolic patterns in ALD rats, and oral FMT could be an effective therapeutic approach for ALD.

Rationale: Sunitinib is a small-molecule tyrosine kinase inhibitor associated with the side-effect of liver injury. The impaired cell type in liver and the hepatotoxicity mechanisms is still unclear. Methods: Spatial metabolomics, transmission electron microscopy, immunofluorescence co-staining, and isolation of bile duct cells and liver sinusoidal endothelial cells (LSECs) were used to evaluate the zonated hepatotoxicity of sunitinib. Farnesoid X receptor (FXR) conditional knockout mice, metagenomics analysis, bacteria clearance, bacterial culture, Parabacteroides distasonis and 3-oxolithocholic acid supplementation were used to evaluate the hepatotoxicity mechanisms of sunitinib. Results: Phenotype analysis found that hepatic autophagy, apoptosis, and mitochondrial injury were observed in vivo or in vitro after sunitinib treatment. By using spatial metabolomics and isolation of bile duct cells and LSECs, the zonated drug toxicity was observed around the portal vein. Hepatocytes, bile duct cells, and LSECs were damaged after sunitinib treatment. FXR inhibition and gut microbiota depletion aggravated sunitinib-induced liver injury. For diurnal variation, sunitinib-induced liver injury was enhanced at night compared with that at day, and FXR and gut microbiota participated in circadian rhythmic hepatotoxicity induced by sunitinib. Conclusions: Our data suggested activation of FXR and Parabacteroides distasonis supplementation may be used to improve sunitinib-induced hepatotoxicity.

Mitigating steatosis is essential for delaying the progression of alcoholic liver disease. The effect and mechanism of Lactiplantibacillus plantarum P101 (LP.P101) on alleviating alcohol-induced hepatic lipid accumulation were investigated in our study. The mouse model was constructed by a short-term (10-day)-plus-binge ethanol feeding and gavaged with 108 CFU/mL of LP.P101 daily. Lipid droplet in the liver was significantly reduced by LP.101 intervention on AMPK activation. However, when AMPK was inhibited by dorsomorphin, the levels of related indicators (ALT, TG, etc.) and the expression levels of AMPK and relevant genes in the liver converged to that of the alcohol-fed group. Compared with the alcohol-fed group, LP.P101 reduced the relative abundance of Firmicutes and increased that of Bacteroidetes. Parabacteroides merdae was negatively correlated with lipid accumulation, and unclassified Negativibacillus was negatively associated with AMPK activation. Importantly, LP.P101 modified the compositions of the serum metabolites. The potential biomarker stercobilinogen was positively correlated with AMPK activation and negatively associated with lipid accumulation. This work confirmed that LP.P101 attenuated alcohol-induced hepatic lipid accumulation in mice through AMPK activation, and the alterations in gut microbiota and metabolites may play a significant role on AMPK activation.

Alcohol-associated liver disease (ALD) is a growing global health concern and its prevalence and severity are increasing steadily. While bacterial endotoxin translocation into the portal circulation is a well-established key factor, recent evidence highlights the critical role of sterile inflammation, triggered by diverse stimuli, in alcohol-induced liver injury. This review provides a comprehensive analysis of the complex interactions within the hepatic microenvironment in ALD. It examines the contributions of both parenchymal cells, like hepatocytes, and non-parenchymal cells, such as hepatic stellate cells, Kupffer cells, neutrophils, and liver sinusoidal endothelial cells, in driving the progression of the disease. Additionally, we explored the involvement of key mediators, including cytokines, chemokines and inflammasomes, which regulate inflammatory responses and promote liver injury and fibrosis. A particular focus has been placed on extracellular vesicles (EVs) as essential mediators of intercellular communication both within and beyond the liver. These vesicles facilitate the transfer of signalling molecules, such as microRNAs and proteins, which modulate immune responses, fibrogenesis and lipid metabolism, thereby influencing disease progression. Moreover, we underscore the importance of organ-to-organ crosstalk, particularly in the gut-liver axis, where dysbiosis and increased intestinal permeability lead to microbial translocation, exacerbating hepatic inflammation. The adipose-liver axis is also highlighted, particularly the impact of adipokines and free fatty acids from adipose tissue on hepatic steatosis and inflammation in the context of alcohol consumption.

Phillygenin (PHI) is an active ingredient derived from the leaf of Forsythia suspensa that has been found to alleviate inflammation and peroxidation response. Avian infectious bronchitis (IB) is a major threat to poultry industry viral respiratory tract disease that infected with infectious bronchitis virus (IBV). This study investigated the protection of PHI to CEK cell and broiler's tracheal injury triggered by avian infectious bronchitis virus (IBV). The results showed that IBV infection did not cause serious clinical symptoms and slowing-body weight in PHI-treated broilers. The expression of virus loads, pro-inflammation factors (IL-6, TNF-α, and IL-1β) in CEK cell, and tracheas were decreased compared to the IBV group, exhibiting its potent anti-inflammation. Mechanistically, the study demonstrated that the inhibition of TLR7/MyD88/NF-κB pathway was mainly involved in the protection effect of PHI to inflammation injury. Interestingly, a higher abundance of Firmicutes and Lactobacillus in respiratory tract was observed in PHI-treated broilers than in the IBV group. Significant differences were observed between the IBV group and PHI-treated group in the Ferroptosis, Tryptophan metabolism, and Glutathione metabolism pathways. PHI exhibited potent protection effect on IBV infection and alleviated inflammation injury, mainly through inhibiting TLR7/MyD88/NF-κB pathway. The study encourages further development of PHI, paving the way to its clinical use as a new candidate drug to relieve IBV-induced respiratory symptoms.

Alcohol is the most widely abused substance in the world, the leading source of mortality in 15-49-year-olds, and a major risk factor for heart disease, liver disease, diabetes, and cancer. Despite this, alcohol is regularly misused in wider society. Consumers of excess alcohol often note a constellation of negative symptoms, known as the alcohol hangover. However, the alcohol hangover is not considered to have long-term clinical significance by clinicians or consumers. We undertook a critical review of the literature to demonstrate the pathophysiological mechanisms of the alcohol hangover. Hereafter, the alcohol hangover is re-defined as a manifestation of sickness behavior secondary to alcohol-induced inflammation, using the Bradford-Hill criteria to demonstrate causation above correlation. Alcohol causes inflammation through oxidative stress and endotoxemia. Alcohol metabolism is oxidative and increased intake causes relative tissue hypoxia and increased free radical generation. Tissue damage ensues through lipid peroxidation and the formation of DNA/protein adducts. Byproducts of alcohol metabolism such as acetaldehyde and congeners, sleep deprivation, and the activation of nonspecific inducible CYP2E1 in alcohol-exposed tissues exacerbate free radical generation. Tissue damage and cell death lead to inflammation, but in the intestine loss of epithelial cells leads to intestinal permeability, allowing the translocation of pathogenic bacteria to the systemic circulation (endotoxemia). This leads to a well-characterized cascade of systemic inflammation, additionally activating toll-like receptor 4 to induce sickness behavior. Considering the evidence, it is suggested that hangover frequency and severity may be predictors of the development of later alcohol-related diseases, meriting formal confirmation in prospective studies. In light of the mechanisms of alcohol-mediated inflammation, research into gut permeability and the gut microbiome may be an exciting future therapeutic avenue to prevent alcohol hangover and other alcohol-related diseases.

Currently, there are no authorized medications specifically for non-alcoholic fatty liver disease (NAFLD) treatment. Studies indicate that changes in gut microbiota can disturb intestinal balance and impair the immune system and metabolism, thereby elevating the risk of developing and exacerbating NAFLD. Despite some debate, the potential benefits of microbial therapies in managing NAFLD have been shown.

A systematic search was undertaken to identify meta-analyses of randomized controlled trials that explored the effects of microbial therapy on the NAFLD population. The goal was to synthesize the existing evidence-based knowledge in this field.

The results revealed that probiotics played a significant role in various aspects, including a reduction in liver stiffness (MD: -0.38, 95% CI: [-0.49, -0.26]), hepatic steatosis (OR: 4.87, 95% CI: [1.85, 12.79]), decrease in body mass index (MD: -1.46, 95% CI: [-2.43, -0.48]), diminished waist circumference (MD: -1.81, 95% CI: [-3.18, -0.43]), lowered alanine aminotransferase levels (MD: -13.40, 95% CI: [-17.02, -9.77]), decreased aspartate aminotransferase levels (MD: -13.54, 95% CI: [-17.85, -9.22]), lowered total cholesterol levels (MD: -15.38, 95% CI: [-26.49, -4.26]), decreased fasting plasma glucose levels (MD: -4.98, 95% CI: [-9.94, -0.01]), reduced fasting insulin (MD: -1.32, 95% CI: [-2.42, -0.21]), and a decline in homeostatic model assessment of insulin resistance (MD: -0.42, 95% CI: [-0.72, -0.11]) (P<0.05).

Overall, the results demonstrated that gut microbiota interventions could ameliorate a wide range of indicators including glycemic profile, dyslipidemia, anthropometric indices, and liver injury, allowing them to be considered a promising treatment strategy.

Algal polysaccharides possess many biological activities and health benefits, such as antioxidant, anti-tumor, anti-coagulant, and immunomodulatory potential. Gut microbiota has emerged as one of the major contributor in mediating the health benefits of algal polysaccharides. In this study we showed that Haematococcus pluvialis polysaccharides (HPP) decreased serum transaminase levels and hepatic triglyceride content, alleviated inflammation and oxidative stress in the liver of chronic and binge ethanol diet-fed mice. Furthermore, HPP reduced endotoxemia, improved gut microbiota dysbiosis, inhibited epithelial barrier disruption and gut vascular barrier (GVB) damage in ethanol diet-fed mice. Co-housing vehicle-fed mice with HPP-fed mice alleviated ethanol-induced liver damage and endotoxemia. Moreover, fecal microbiota transplantation from HPP-fed mice into antibiotic-induced microbiota-depleted recipients also alleviated ethanol-induced liver injury and improved gut epithelial and vascular barrier. Our study demonstrated that HPP ameliorated ethanol-induced gut epithelial and vascular barrier dysfunction through alteration of gut microbiota, therefore preventing alcoholic liver damage.

Probiotics can regulate gut microbiota and protect against acute alcohol-induced liver injury through the gut-liver axis. However, efficacy is strain-dependent, and their mechanism remains unclear. This study investigated the effect of lactic acid bacteria (LAB), including Lacticaseibacillus paracasei E10 (E10), Lactiplantibacillus plantarum M (M), Lacticaseibacillus rhamnosus LGG (LGG), Lacticaseibacillus paracasei JN-1 (JN-1), and Lacticaseibacillus paracasei JN-8 (JN-8), on the prevention of acute alcoholic liver injury in mice. We found that LAB pretreatment reduced serum alanine transaminase (ALT) and aspartate transaminase (AST) and reduced hepatic total cholesterol (TC) and triglyceride (TG). JN-8 pretreatment exhibited superior efficacy in improving hepatic antioxidation. LGG and JN-8 pretreatment significantly attenuated hepatic and colonic inflammation by decreasing the expression of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) and increasing the expression of interleukin 10 (IL-10). JN-1 and JN-8 pretreatments have better preventive effects than other LAB pretreatment on intestinal barrier dysfunction. In addition, the LAB pretreatment improved gut microbial dysbiosis and bile acid (BA) metabolic abnormality. All of the strains were confirmed to have bile salt deconjugation capacities in vitro, where M and JN-8 displayed higher activities. This study provides new insights into the prevention and mechanism of LAB strains in preventing acute alcoholic liver injury.

Alcoholic liver damage is caused by long-term or heavy drinking, and it may further progress into alcoholic liver diseases (ALD). Probiotic supplements have been suggested for the prevention or improvement of liver damage. This study was designed to consider the ameliorative effects of Lactobacillus rhamnosus NKU FL1-8 isolated from infant feces against alcoholic liver damage. The mice were gavaged with a 50% ethanol solution and treated with 109 CFU of L. rhamnosus NKU FL1-8 suspension. The factors for liver function, oxidative stress, inflammation, gut microbiota composition, and intestinal barrier integrity were measured. The results showed that L. rhamnosus NKU FL1-8 could decrease the levels of aspartate aminotransferase (AST) to 61% and alanine aminotransferase (ALT) to 50% compared with ethanol given by gavage. It could inhibit the expression level of malondialdehyde (MDA), increase superoxide dismutase (SOD), glutathione (GSH) to relieve oxidative stress, and down-regulate the cytokines to decrease hepatic inflammation. After treatment, the level of triglycerides was reduced, and the expression levels of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and the peroxisome proliferators-activated receptor-α (PPAR-α) pathway were up-regulated. Additionally, the 16S rRNA sequencing analysis showed that L. rhamnosus NKU FL1-8 increased the relative abundance of Lactobacillus, Ruminococcaceae, etc. At the same time, L. rhamnosus NKU FL1-8 could significantly reduce lipopolysaccharides (LPS) and enhance intestinal tight junction proteins. These results demonstrated that L. rhamnosus NKU FL1-8 could reduce the level of oxidative stress, fat accumulation, and liver inflammation caused by alcohol in the host. The underlying mechanism could be that L. rhamnosus NKU FL1-8 inhibits LPS by regulating the gut microbiota and repairing the intestinal barrier. Thereby, these findings support L. rhamnosus NKU FL1-8 as a potential functional food for the relief of ALD.

Evidence suggests that a relationship exists between the gut microbiome and the pathogenesis of alcohol use disorder (AUD) and alcohol-associated liver disease (AALD). This systematic review identified studies that investigated the gut microbiome in individuals with an AUD or an AALD. A search was conducted on October 27, 2022, in PubMed, Web of Science, and Embase databases. Fifty studies satisfied eligibility criteria. Most studies found evidence for gut dysbiosis in individuals with AUD and AALD. Microbiome intervention studies have mostly been conducted in AALD patients; fecal microbial transplant interventions show the most promise. Because most studies were conducted cross-sectionally, the causal relationship between the gut microbiome and alcohol use is unknown. Furthermore, almost all studies have been conducted in predominantly male populations, leaving critical questions regarding sex differences and generalizability of the findings. The study summaries and recommendations provided in this review seek to identify areas for further research and to highlight potential gut microbial interventions for treating AUD and AALD.

Myriad associations between the microbiome and various facets of liver physiology and pathology have been described in the literature. Building on descriptive and correlative sequencing studies, metagenomic studies are expanding our collective understanding of the functional and mechanistic role of the microbiome as mediators of the gut-liver axis. Based on these mechanisms, the functional activity of the microbiome represents an attractive, tractable, and precision medicine therapeutic target in several liver diseases. Indeed, several therapeutics have been used in liver disease even before their description as a microbiome-dependent approach. To bring successful microbiome-targeted and microbiome-inspired therapies to the clinic, a comprehensive appreciation of the different approaches to influence, collaborate with, or engineer the gut microbiome to coopt a disease-relevant function of interest in the right patient is key. Herein, we describe the various levels at which the microbiome can be targeted-from prebiotics, probiotics, synbiotics, and antibiotics to microbiome reconstitution and precision microbiome engineering. Assimilating data from preclinical animal models, human studies as well as clinical trials, we describe the potential for and rationale behind studying such therapies across several liver diseases, including metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, cirrhosis, HE as well as liver cancer. Lastly, we discuss lessons learned from previous attempts at developing such therapies, the regulatory framework that needs to be navigated, and the challenges that remain.

The gut microbiota is constituted by trillions of microorganisms colonizing the human intestine. Studies conducted in patients with alcohol use disorder (AUD) have shown altered microbial composition related to bacteria, viruses, and fungi.This review describes the communication pathways between the gut and the brain, including the ones related to the bacterial metabolites, the inflammatory cytokines, and the vagus nerve. We described in more detail the gut-derived metabolites that have been shown to be implicated in AUD or that could potentially be involved in the development of AUD due to their immune and/or neuroactive properties, including tryptophan-derivatives, tyrosine-derivatives, short chain fatty acids.Finally, we discussed the potential beneficial effects of microbiome-based therapies for AUD such as probiotics, prebiotics, postbiotic, and phage therapy.

It is becoming increasingly apparent that commensal skin bacteria have an important role in wound healing and infection progression. However, the precise mechanisms underpinning many of these probiotic interactions remain to be fully uncovered. In this work, we demonstrate that the common skin commensal Cutibacterium acnes can limit the pathogenicity of the prevalent wound pathogen Pseudomonas aeruginosa in vivo. We show that this impact on pathogenicity is independent of any effect on growth, but occurs through a significant downregulation of the Type Three Secretion System (T3SS), the primary toxin secretion system utilised by P. aeruginosa in eukaryotic infection. We also show a downregulation in glucose acquisition systems, a known regulator of the T3SS, suggesting that glucose availability in a wound can influence infection progression. C. acnes is well known as a glucose fermenting organism, and we demonstrate that topically supplementing a wound with glucose reverses the probiotic effects of C. acnes. This suggests that introducing carbon source competition within the wound microenvironment may be an effective way to prevent or limit wound infection.

Neonatal jaundice is a common and life-threatening health problem in neonates due to overaccumulation of circulating unconjugated bilirubin. Gut flora has a potential influence on bilirubin metabolism. The infant gut microbiome is commonly copied from the maternal gut. During pregnancy, due to changes in dietary habits, hormones and body weight, maternal gut dysbiosis is common, which can be stabilised by probiotics supplementation. However, whether probiotic supplements can reach the baby through the mother and reduce the incidence of neonatal jaundice has not been studied yet. Therefore, we aim to evaluate the effect of prenatal maternal probiotic supplementation on the incidence of neonatal jaundice.

This is a randomised double-blind placebo-controlled clinical trial among 94 pregnant women (47 in each group) in a tertiary hospital in Hong Kong. Voluntary eligible participants will be recruited between 28 and 35 weeks of gestation. Computer-generated randomisation and allocation to either the intervention or control group will be carried out. Participants will take either one sachet of Vivomixx (450 billion colony-forming units per sachet) or a placebo per day until 1 week post partum. Neither the study participants nor researchers will know the randomisation and allocation. The intervention will be initiated at 36 weeks of gestation. Neonatal bilirubin level will be measured to determine the primary outcome (hyperbilirubinaemia) while the metagenomic microbiome profile of breast milk and maternal and infant stool samples as well as pregnancy outcomes will be secondary outcomes. Binary logistic and linear regressions will be carried out to assess the association of the microbiome data with different clinical outcomes.

Ethics approval is obtained from the Joint CUHK-NTEC Clinical Research Ethics Committee, Hong Kong (CREC Ref: 2023.100-T). Findings will be published in peer-reviewed journals and presented at international conferences.

NCT06087874.

An increased incidence of liver diseases has been observed in recent years and is associated with gut dysbiosis, which causes bacterial infection, intestinal permeability, and further leads to disease-related complications. Probiotics, active microbial strains, are gaining more clinical importance due to their beneficial effect in the management of many diseases, including liver diseases. Clinical scenarios show strong evidence that probiotics have efficacy in treating liver diseases due to their ability to improve epithelial barrier function, prevent bacterial translocation, and boost the immune system. Moreover, probiotics survive both bile and gastric acid to reach the gut and exert their health benefit. Evidence shows that probiotics are a promising approach to prevent several complications in clinical practice. Herein, we discuss the recent evidence, challenges, and appropriate use of probiotics in managing advanced liver diseases, which may have an impact on future therapeutic strategies. Furthermore, the superior effect of strain-specific probiotics and their efficacy and safety in managing liver diseases are discussed.

Probiotic adjuvant has promising effects in treating alcohol induced hepatitis, depression, and anxiety. This study aimed to assess the effectiveness of adjuvant probiotic use in improving the liver functions, anxiety, and depression among patients with alcohol dependence syndrome (ADS) in a tertiary care hospital in Andhra Pradesh, India. In this prospective observational design, ADS patients with or without probiotics were followed-up at one and three months after initiation of treatment. They were assessed for liver function test (LFT), anxiety by HAM-A and depression by HAM-D scale. A total of 120 patients complied with the treatment, 60 in each group, mean age being 35.0 years (SD 9.5 years). The baseline socio-demographic and clinical characteristics were similar in both the groups. Significant reduction was noted in the probiotic group for total bilirubin (Mean difference (MD) 0.18; 95 % CI: 0.04, 0.31), AST (MD 5.0; 95 % CI: 0.5, 9.5), and ALT (MD 8.6; 95 % CI: 1.4, 15.7) at one month after treatment. Both the groups showed a considerable change in anxiety and depression scores (HAM-A and HAM-D) till three months. At three months of treatment initiation, proportional improvement of severity grade to mild form in anxiety was more in the probiotic group (35 %) than the non-probiotic group (13.3 %) (p < 0.05). Hence, probiotic supplementation can significantly reduce the hepatic enzymes and depression severity in patients with alcohol dependence syndrome but demands additional robust evidence on the causal inference.

A dual NIR fluorescent probe Cy-ND is developed for viscosity sensing with λex/em = 766/806 nm, making it apt for biological analysis, whose response is validated through DFT and TDDFT computations. Cy-ND successfully detected viscosity changes amidst acute alcohol-induced liver injury and liver ischemia-reperfusion injury.

The gut microbiota, amounting to approximately 100 trillion (1014) microbes represents a genetic repertoire that is bigger than the human genome itself. Evidence on bidirectional interplay between human and microbial genes is mounting. Microbiota probably play vital roles in diverse aspects of normal human metabolism, such as digestion, immune modulation, and gut endocrine function, as well as in the genesis and progression of many human diseases. Indeed, the gut microbiota has been most closely linked to various chronic ailments affecting the liver, although concrete scientific data are sparse. In this narrative review, we initially discuss the basic epidemiology of gut microbiota and the factors influencing their initial formation in the gut. Subsequently, we delve into the gut-liver axis and the evidence regarding the link between gut microbiota and the genesis or progression of various liver diseases. Finally, we summarise the recent research on plausible ways to modulate the gut microbiota to alter the natural history of liver disease.

In recent years, an increasing attention has given to the intricate and diverse connection of microorganisms residing in our gut and their impact on brain health and central nervous system disease. There has been a shift in mindset to understand that drug addiction is not merely a condition that affects the brain, it is now being recognized as a disorder that also involves external factors such as the intestinal microbiota, which could influence vulnerability and the development of addictive behaviors. Furthermore, stress and social interactions, which are closely linked to the intestinal microbiota, are powerful modulators of addiction. This review delves into the mechanisms through which the microbiota-stress-immune axis may shape drug addiction and social behaviors. This work integrates preclinical and clinical evidence that demonstrate the bidirectional communication between stress, social behaviors, substance use disorders and the gut microbiota, suggesting that gut microbes might modulate social stress having a significance in drug addiction.

Excessive alcohol consumption can have serious negative consequences on health, including addiction, liver damage, and other long-term effects. The causes of hangovers include dehydration, alcohol and alcohol metabolite toxicity, and nutrient deficiency due to absorption disorders. Additionally, alcohol consumption can slow reaction times, making it more difficult to rapidly respond to situations that require quick thinking. Exposure to a large amount of ethanol can also negatively affect a person's righting reflex and balance. In this study, we evaluated the potential of lactic acid bacteria (LAB) to alleviate alcohol-induced effects and behavioral responses. Two LAB strains isolated from kimchi, Levilactobacillus brevis WiKim0168 and Leuconostoc mesenteroides WiKim0172, were selected for their ethanol tolerance and potential to alleviate hangover symptoms. Enzyme activity assays for alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) were then conducted to evaluate the role of these bacteria in alcohol metabolism. Through in vitro and in vivo studies, these strains were assessed for their ability to reduce blood alcohol concentrations and protect against alcohol-induced liver damage. The results indicated that these LAB strains possess significant ethanol tolerance and elevate ADH and ALDH activities. LAB administration remarkably reduced blood alcohol levels in rats after excessive alcohol consumption. Moreover, the LAB strains showed hepatoprotective effects and enhanced behavioral outcomes, highlighting their potential as probiotics for counteracting the adverse effects of alcohol consumption. These findings support the development of functional foods incorporating LAB strains that can mediate behavioral improvements following alcohol intake.

Alcohol use disorder (AUD) represents a major public health issue which affects millions of people globally and consist a chronic relapsing condition associated with substantial morbidity and mortality. The gut microbiome plays a crucial role in maintaining overall health and has emerged as a significant contributor to the pathophysiology of various psychiatric disorders. Recent evidence suggests that the gut microbiome is intimately linked to the development and progression of AUD, with alcohol consumption directly impacting its composition and function. This review article aims to explore the intricate relationship between the gut microbiome and AUD, focusing on the implications for mental health outcomes and potential therapeutic strategies. We discuss the bidirectional communication between the gut microbiome and the brain, highlighting the role of microbiota-derived metabolites in neuroinflammation, neurotransmission, and mood regulation. Furthermore, we examine the influence of AUD-related factors, such as alcohol-induced gut dysbiosis and increased intestinal permeability, on mental health outcomes. Finally, we explore emerging therapeutic avenues targeting the gut microbiome in the management of AUD, including prebiotics, probiotics, and fecal microbiota transplantation. Understanding the complex interplay between the gut microbiome and AUD holds promise for developing novel interventions that could improve mental health outcomes in individuals with AUD.

Alcoholic liver disease (ALD) is a liver damage disease caused by long-term heavy drinking. Currently, there is no targeted pharmaceutical intervention available for the treatment of this disease. To address this, this paper evaluates the efficacy and safety of probiotic preparation in treating ALD through conducting a meta-analysis, and provides a valuable insight for clinical decision-making.

A systematic search was conducted across databases, including PubMed, Embase, Web of Science, Cochrane Library, CNKI, VIP, Wanfang, and CBM from the inception dates to October 15, 2023, to identify clinical randomized controlled trials on probiotic preparations in the treatment of ALD. After the literature underwent screening, data extraction, and quality assessment, RevMan 5.3 and Stata 14.2 were employed for data analysis and processing.

A total of 9 randomized controlled trials fulfilled the inclusion criteria. The results of the meta-analysis showed that probiotic preparation could significantly improve the liver function of patients with alcoholic liver disease compared with the control group. Probiotic intervention led to a significant reduction in the levels of alanine aminotransferase (MD=-13.36,95%CI:-15.80,-10.91;P<0.00001),aspartate aminotransferase (MD=-16.99,95%CI:-20.38,-13.59;P<0.00001),γ-glutamyl transpeptidase (MD=-18.79,95% CI:-28.23,-9.34; P<0.0001). Concurrently, the level of serum albumin (MD=0.19,95% CI:0.02,0.36;P=0.03) was increased. Furthermore, probiotic intervention could also modulate the composition of intestinal flora in patients with alcoholic liver disease, leading to an augmentation in Bifidobacteria and a reduction in Escherichia coli. However, in patients with alcoholic liver disease, probiotic intervention showed no significant effects on total bilirubin (MD=-0.01,95% CI:-0.17,0.15;P=0.91), tumor necrosis factor-α (MD=0.03,95% CI:-0.86,0.92;P=0.94) and interleukin-6 (MD=-5.3,95% CI:-16.04,5.45;P=0.33).

The meta-analysis indicates that probiotics can improve liver function in alcoholic liver disease, reduce inflammatory responses, regulate intestinal flora, which have potential value in the treatment of alcoholic liver disease.

https://www.crd.york.ac.uk/prospero/, identifier CRD42023472527.

Probiotics have shown the potential to counteract the loss of muscle mass, reduce physical fatigue, and mitigate inflammatory response following intense exercise, although the mechanisms by which they work are not very clear. The objective of this review is to describe the main harmful effects of alcohol on skeletal muscle and to provide important strategies based on the use of probiotics. The excessive consumption of alcohol is a worldwide problem and has been shown to be crucial in the progression of alcoholic liver disease (ALD), for which, to date, the only therapy available is lifestyle modification, including cessation of drinking. In ALD, alcohol contributes significantly to the loss of skeletal muscle, and also to changes in the intestinal microbiota, which are the basis for a series of problems related to the onset of sarcopenia. Some of the main effects of alcohol on the skeletal muscle are described in this review, with particular emphasis on the "gut-liver-muscle axis", which seems to be the primary cause of a series of muscle dysfunctions related to the onset of ALD. The modulation of the intestinal microbiota through probiotics utilization has appeared to be crucial in mitigating the muscle damage induced by the high amounts of alcohol consumed.

Alcohol use disorder (AUD) is associated with significant psychological and economic burdens, as well as physical comorbidities that can lead to death. Previous research has found that probiotics may reduce inflammatory biomarkers in persons with AUD and comorbid conditions such as cirrhosis of the liver. This relationship has not been explored in heavy drinkers without comorbid conditions. In a proof-of-concept study, individuals who were heavy drinkers without known comorbidities received a 30-day course of a daily probiotic supplement in an open-label pilot trial. Eligible participants (N = 16) met NIAAA guidelines for heavy alcohol use and did not report any preexisting medical problems. Blood samples were taken at four timepoints: prior to the probiotic course, at the midpoint, at the end, and after a washout period of at least one month. Immunoassays were conducted on plasma samples to quantify the following inflammatory biomarkers: IL-6, IL-8, IL-10, LBP, MCP-1, sCD14, sCD163, and TNF-α. Linear mixed models were used to test within-subjects changes in biomarker concentrations over the study period, with alcohol use included as a time-varying covariate. Biomarker concentrations did not change significantly. A higher number of heavy drinking days was statistically associated with higher concentrations of IL-6 (F(1,8) = 6.66, p = 0.0326) and IL-8 (F(1,17) = 6.38, p = 0.0218). Greater days since last drink was associated with a lower concentration of MCP-1 (F(1,17) = 5.77, p = 0.028). In summary, biomarker trajectories were associated with alcohol consumption variables, but not probiotic use, in this open-label pilot study. Randomized controlled trials are needed to evaluate fully the potential benefits of probiotics in heavy drinkers without known comorbidities and under conditions of non-abstinence.

Chronic alcohol use is a major cause of liver damage and death. In the United States, multiple factors have led to low utilization of pharmacotherapy for alcohol use disorder (AUD), including lack of provider knowledge and comfort in prescribing medications for AUD. Alcohol consumption has direct effects on the gut microbiota, altering the diversity of bacteria and leading to bacterial overgrowth. Growing evidence suggests that alcohol's effects on the gut microbiome may contribute to increased alcohol consumption and progression of alcohol-associated liver disease (ALD). This article reviews human and preclinical studies investigating the role of fecal microbiota transplantation (FMT) in ameliorating alcohol-associated alterations to the liver, gut, and brain resulting in altered behavior; it also discusses the therapeutic potential of FMT.

For this narrative review, a literature search was conducted in September 2022 of PubMed, Web of Science Core Collection, and Google Scholar to identify studies published between January 2012 and September 2022. Search terms used included "fecal microbiota transplantation" and "alcohol."

Most results of the literature search were review articles or articles on nonalcoholic fatty liver disease; these were excluded. Of the remaining empirical manuscripts, very few described clinical or preclinical studies that were directly investigating the effects of FMT on alcohol drinking or related behaviors. Ultimately, 16 studies were included in the review.

The literature search identified only a few studies that were directly investigating the effect of FMT on ALD or alcohol drinking and related behaviors. Largely proof-of-concept studies, these findings demonstrate that alcohol can alter the gut microbiome and that the microbiome can be transferred between humans and rodents to alter affective behaviors frequently associated with increased alcohol use. Other studies have shown promise of FMT or other probiotic supplementation in alleviating some of the symptoms associated with ALD and drinking. These results show that the implementation of FMT as a therapeutic approach is still in the investigatory stages.

The microbiome is a critical factor in health throughout human development. The aims of this scoping review are to (i) elucidate the differences between the youth (post-natal day 21-65 for rodents, 2-7 years for non-human primates, and 10-25 years for humans) microbiome with other life stages and (ii) identify youth-specific microbial changes associated with substance use.

Peer-reviewed studies published up to May 2023 were identified in PubMed and SCOPUS and included gut and oral microbiome studies from rodents, non-human primates, and humans (N = 1733). Twenty-six articles were determined eligible based on inclusion criteria (aim 1: n = 19, aim 2: n = 7).

The adolescent and young adult oral and gut microbiomes are distinct compared to other life stages, within both non-human and human models. While there is limited research in this area, the microbiome appears to be vulnerable to substance use exposure earlier in life, including substances commonly initiated and escalated during adolescence and young adulthood (i.e. alcohol, cannabis, and tobacco).

Studies across the lifespan indicate that adolescence and young adulthood are distinct periods of development, where the microbiome is sensitive to exposures, including substance use. There is a need for more studies focused on the adolescent and young adult microbiome and substance use, as well as focused on the oral microbiome during this developmental period. Understanding the gut and oral microbiome during adolescence and young adulthood may provide insight into the pathophysiology of substance use disorders.

Objective: To systematically evaluate the efficacy of intestinal microbiome-targeted therapies (MTTs) in alcohol-related liver disease (ALD). Methods: With pre-specified keywords and strategies, we searched databases including Cochrane Library, PubMed, EMBASE, CNKI, Wanfang Data, and Weipu for RCTs on intestinal MTTs in ALD patients from January 2000 to May 2021. Two researchers independently conducted literature screening, data extraction, and quality evaluation according to the eligible criteria. Outcomes of interest included the effects of intestinal MTTs on ALT, AST, GGT, TBIL, TNF-α, IL-6, intestinal Escherichia coli, and Bifidobacteria when compared to the control group. Pooled data were compiled and analyzed with Revman 5.4 software. Results: Among 5 RCTs included with 456 ALD patients who received probiotics, the therapeutic pooled effects in the experimental group were the followings: ALT (MD = -7.16.95% CI: 10.71∼-3.60; p < 0.0001)、AST (MD = -25.11.95% CI: 30.57∼-19.47; p < 0.00001)、GGT (MD = -6.72.95% CI: 11.91∼-1.53; p = 0.01)、IL-6(SMD = -0.82.95% CI: 1.10∼-0.54; p < 0.00001), which were significantly better than those in the placebo or standard treatment group respectively, while the difference of TBIL (SMD = -0.06, 95%CI: 0.29-0.16; p = 0.59), TNF-α(SMD = -0.53.95% CI: 1.57-0.50; p = 0.31)in the two groups was not significant. After intestinal MTT treatment, the number of intestinal Bifidobacteria increased significantly (MD = 0.79.95% CI: 0.00-1.58; p = 0.05)in the experimental group. However, there were no significant changes in the number of E. coli in both groups (SMD = -0.29.95% CI: 0.92-0.34; p = 0.36). Conclusion: Intestinal MTTs can significantly improve liver function, associated with the increase of intestinal Bifidobacteria, which may be beneficial to ALD. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021246067, Identifier CRD42021246067.

Alcohol-associated liver disease (ALD) is the most common cause of advanced hepatic disease and frequent indication for liver transplantation worldwide. With harmful alcohol use as the primary risk factor, increasing alcohol use over the past decade has resulted in rapid growth of the ALD-related healthcare burden. The spectrum of ALD ranges from early asymptomatic liver injury to advanced disease with decompensation and portal hypertension. Compared with those with other etiologies of liver disease, patients with ALD progress faster and more often present at an advanced stage. A unique phenotype of advanced disease is alcohol-associated hepatitis (AH) presenting with rapid onset or worsening of jaundice, and acute on chronic liver failure in severe forms conveying a 1-month mortality risk of 20%-50%. The model for end stage disease score is the most accurate score to stratify AH severity (>20 defined as severe disease). Corticosteroids are currently the only available therapeutic with proven efficacy for patients with severe AH, providing survival benefit at 1 month in 50%-60% of patients. Abstinence of alcohol use, a crucial determinant of long-term outcomes, is challenging to achieve in ALD patients with concurrent alcohol use disorder (AUD). As patients with ALD are rarely treated for AUD, strategies are needed to overcome barriers to AUD treatment in patients with ALD and to promote a multidisciplinary integrated care model with hepatology, addiction medicine providers, and social workers to comprehensively manage the dual pathologies of liver disease and of AUD. Liver transplantation, a definitive treatment option in patients with advanced cirrhosis, should be considered in selected patients with AH, who are unresponsive to medical therapy and have a low risk of relapse to posttransplant alcohol use. Level of evidence and strength of recommendations were evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations system. This guideline was developed under the American College of Gastroenterology Practice Parameters Committee.

Allergic illnesses occur when an organism's immune system is excessively responsive to certain antigens, such as those that are presented in the environment. Some people suffer from a wide range of immune system-related illnesses including allergic rhinitis, asthma, food allergies, hay fever, and even anaphylaxis. Immunotherapy and medications are frequently used to treat allergic disorders. The use of probiotics in bacteriotherapy has lately gained interest. Probiotics are essential to human health by modulating the gut microbiota in some ways. Due to probiotics' immunomodulatory properties present in the gut microbiota of all animals, including humans, these bacterial strains can prevent a wide variety of allergic disorders. Probiotic treatment helps allergy patients by decreasing inflammatory cytokines and enhancing intestinal permeability, which is important in the battle against allergy. By altering the balance of Th1 and Th2 immune responses in the intestinal mucosa, probiotics can heal allergic disorders. Numerous studies have shown a correlation between probiotics and a reduced risk of allergy disorders. A wide range of allergic disorders, including atopic dermatitis, asthma, allergic retinitis and food allergies has been proven to benefit from probiotic bacteria. Therefore, the use of probiotics in the treatment of allergic diseases offers a promising perspective. Considering that probiotic intervention in the treatment of diseases is a relatively new field of study, more studies in this regard seem necessary.