Alcohol consumption is responsible for approximately 6% of all deaths and 5.1% of the global disease burden. The most common alcohol-related causes of death include liver cirrhosis (50% of cases), pancreatitis (25%), and esophageal cancer (22%). In this review, we provide an overview of ethanol metabolism and highlight the major diseases caused by alcohol consumption in the liver and gastrointestinal tract. Due to its central metabolic role, the liver is particularly susceptible to ethanol, which is known to cause a wide spectrum of conditions, including steatosis, steatohepatitis, alcohol-associated hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma). The gastrointestinal tract is often one of the first areas to show signs of damage from excessive alcohol consumption. Chronic alcohol abuse is a well-established risk factor for both acute and chronic pancreatitis, as well as pancreatic cancer. Approximately 70% of acute pancreatitis cases and 30% of chronic pancreatitis cases are attributable to alcohol abuse. Epidemiological studies have consistently demonstrated a positive correlation between alcohol intake and the prevalence of gallstones. Moreover, alcohol is an important risk factor for gastroenteropancreatic cancer, as ethanol metabolism produces acetaldehyde, a potent carcinogen for humans. In conclusion, chronic ethanol intake, through one of its main metabolic products, acetaldehyde, causes pathological changes in the gastrointestinal tract, liver, pancreas, and gallbladder. Even moderate amounts of alcohol may increase the risk of cancers, such as colorectal cancer. Therefore, if there is clinical suspicion of excessive alcohol intake in a patient with persistent digestive symptoms (e.g., abdominal pain, nausea, vomiting, diarrhea, and bloody stools), immediate medical evaluation is essential. Referral to specialized centers with expertise in alcohol use disorder is a key management option for patients with established alcohol use disorder.

Percutaneous endoscopic gastrostomy (PEG) tube placement is a common procedure used to provide medium- and long-term enteral nutrition to patients. Although generally considered safe, PEG tube placement can be associated with various potential complications. We report a case of gastrocolocutaneous fistula formation in a patient who presented with severe abdominal pain, new-onset diarrhea, and feculent emesis nine days after PEG tube placement. Awareness of this rare complication can facilitate the recognition of colonic perforation during gastrostomy tube placement and enable early detection of the complication post-procedurally. Additionally, we discuss various techniques that may be employed to prevent this complication during PEG tube placement.

Based on our experimental and clinical research, the gastroschisis is formed by raised intraluminal and intraabdominal pressure in combination with potential weak points. The psycho-neuro-endocrine-target organ axis of young mothers, who themselves struggle to meet their macro and micronutrient requirements, places a burden on the placenta. The associated smoking, alcohol, drugs, and other toxins, leads to fetal distress. This activates the same fetal axis, with the final common pathway being activated via the sacral parasympathetic nervous system as a flight or fight response leading to colorectal secreto-motility disorder of the hindgut and small left colon leading to partial functional obstruction of hindgut. This leads to pressure build-up on the proximal colon. An intact ileocecal valve leads to blind loop obstruction, creating the force required to herniate the bowel through the defect at three key points of weakness in the abdominal wall, the most vulnerable being the right paraumbilical region. If the ileocecal valve becomes incompetent, variants of gastroschisis may occur. The fetus, particularly the peritoneum, always has a tendency to heal defects quickly, which forms secondary events in the eviscerated bowel causing the closing and closed gastroschisis with vanishing organs. Recent technological advances in preformed silastic silo innovation, prenatal diagnosis and monitoring for closing gastroschisis, perinatal management, percutaneous central long lines, and innovative minimally invasive bedside procedures, have all made significant contributions. We believe that gastroschisis is the external surgical symptom and peak of the iceberg, secondary to an underlying colorectal motility disorder, providing the force to eviscerate bowel loops through potential weak points and its subsequent sequelae.

Gluten has multiple harmful effects that compromise human health, not only in gluten-dependent diseases but also in non-gluten-affected chronic inflammatory conditions. After consumption, the indigestible gluten peptides are modified by luminal microbial transglutaminase or transported through the gut epithelium to interact with the highly populated mucosal immune cells. As a disruptor of gut permeability, gluten peptides compromise tight junction integrity, allowing foreign immunogenic molecules to reach internal compartments. Gliadin peptides are distributed systemically to remote organs, where they encounter endogenous tissue transglutaminase. Following post-translational deamidation or transamidation, the peptides become immunogenic and pro-inflammatory, inducing organ dysfunction and pathology. Cross-reactivity and sequence homology between gluten/gliadin peptides and human epitopes may contribute to molecular mimicry in autoimmunity induction. A gluten-free diet can prevent these phenomena through various mechanisms. As proof of concept, gluten withdrawal alleviates disease activity in chronic inflammatory, metabolic, and autoimmune conditions, and even in neurodegeneration. We recommend combining the gluten-free and Mediterranean diets to leverage the advantages of both. Before recommending gluten withdrawal for non-gluten-dependent conditions, patients should be asked about gut symptomatology and screened for celiac-associated antibodies. The current list of gluten-induced diseases includes celiac disease, dermatitis herpetiformis, gluten ataxia, gluten allergy, and non-celiac gluten sensitivity. In view of gluten being a universal pro-inflammatory molecule, other non-celiac autoinflammatory and neurodegenerative conditions should be investigated for potential gluten avoidance.

The gastrointestinal microbiome remains an explosively increasing topic of study, assessing the potentially pivotal roles of the microbiome in maintaining health or causality in disease pathogenesis. Gastroesophageal reflux disease (GERD) has long been understood to be a result of direct acidic injury. However, emerging evidence suggests that GERD could also be caused by alterations in the esophageal microbiome, causing an induction of a submucosal inflammatory cytokine cascade, that has a retrograde effect on the luminal mucosa. This concept of a microbial shift/dysbiosis in the causality of GERD is clearly a paradigm shift and has led to possible treatment strategies beyond the traditional approach of acid-suppressive therapies. This review focuses on the current evidence surrounding GERD and the rationale for possible esophageal microbiome-directed treatment strategies.

Obesity is a complex disease resulting from excessive adipose tissue in the body, leading to various metabolic, mechanical, and psychological complications. The prevalence of obesity has increased exponentially in the past few decades to reach an epidemic proportion. Obesity can predispose to or aggravate the fatty liver. Metabolic dysfunction-associated fatty liver disease (MAFLD) represents fatty liver in individuals who are either overweight/obese, or have type 2 diabetes, or have normal weight with at least two metabolic risk factors. MAFLD pathogenesis is multifactorial and involves an interplay of genetics, lifestyle-related factors, gut dysbiosis, lipotoxicity, and oxidative stress. Besides hepatic complications, MAFLD also has systemic implications in the form of increased risk for various metabolic diseases, cardiovascular diseases, malignancies, and infectious diseases. If left untreated, MAFLD can progress to liver cirrhosis and end-stage liver disease. Many noninvasive strategies like serum-based markers and imaging help diagnose MAFLD at an early stage. Timely detection and appropriate intervention are crucial for preventing its progression to advanced liver disease and hepatocellular carcinoma. Though lifestyle modification remains the main pillar of management, with advances in the treatment of obesity, newer agents are being tried for patients with MAFLD. The current therapeutic strategies are limited, and future research is needed to identify the subset of patients with MAFLD who are at a higher risk of hepatic and systemic complications and to develop more effective and personalized therapies.