Iron deposition in gastric black spots: Clinicopathological insights and NanoSuit-correlative light and electron microscopy analysis.

Objectives: Black spots (BSs) are lentiginous findings observed in the gastric body and fundus during upper gastrointestinal endoscopy and are predominantly seen in patients undergoing Helicobacter pylori eradication treatment. However, the detailed patient background and exact composition are poorly understood. This study aims to clarify the clinicopathological features of BSs, examine patient demographics, and use the NanoSuit-correlative light and electron microscopy (CLEM) method combined with scanning electron microscopy-energy dispersive X-ray spectroscopy for elemental analysis. Methods: Patients who underwent upper gastrointestinal endoscopy between 2017 and 2022 were included. Data on age, medications, blood tests, and H. pylori infection status were retrospectively gathered from medical records. Univariate analysis was conducted to examine BS presence, with results then used in a multivariate model to identify associated risk factors. Additionally, pathological specimens from patients with BSs were analyzed for elemental composition using the NanoSuit-CLEM method combined with scanning electronmicroscopy-energy dispersive X-ray spectroscopy. Results: An analysis of 6778 cases identified risk factors for BSs, including older age and using proton pump inhibitors, statins, corticosteroids, and antithrombotic drugs. Endoscopically, BSs correlated with higher gastric atrophy and lower active H. pylori infection. Iron deposition at BS sites was specifically identified using NanoSuit-CLEM. Conclusions: BSs on gastrointestinal endoscopy may indicate an absence of active H. pylori inflammation. The discovery of iron deposition within BSs using the NanoSuit-CLEM method has offered new insights into the possible causative factors and advances our understanding of the etiology of BSs, bringing us closer to unraveling the underlying mechanisms of their formation.

Gastric carcinoma of the fundic gland type developed 32 years after Helicobacter pylori eradication for duodenal ulcer: a case report.

Introduction: Gastric cancer has been reported to occur with mild to moderate mucosal atrophy, particularly after the eradication of Helicobacter pylori (HP) more than 10 years previously. However, no conclusion has been reached on how many years of esophagogastroduodenoscopy should be performed after HP eradication. Presentation of case: This was a case of gastric carcinoma of the fundic gland type (GCFGT) 32 years after the eradication of HP, which is the longest posteradication period reported. A 62-year-old male patient was diagnosed with GCFGT after HP eradication and regular esophagogastroduodenoscopy, which revealed a white raised lesion on the anterior wall of the upper part of the body. Endoscopic submucosal dissection was performed for GCFGT, and the vertical and horizontal margins were negative. Clinical discussion: In this case, HP was eradicated in 1990, and GCFGT developed 32 years later. To the best of our knowledge, this is the longest case in which gastric cancer appeared after HP eradication. HP eradication therapy for a duodenal ulcer was first reported in 1990, supporting that this is the longest case. Conclusions: This is the first case of gastric cancer more than 20 years after the eradication of HP. The endoscopic findings of this case are typical of GCFGT and may be useful when encountering such cases in the future. Therefore, the risk of gastric cancer should be considered for an extended period even after the eradication of HP, and regular esophagogastroduodenoscopy is recommended even after the eradication of HP.

Changes in the tissue elements of the gastric mucosa interacting with different strains of Helicobacter pylori, taking into consideration the patient's genotype.

The present study aimed to investigate the peculiarities of adaptation of tissue elements of the gastric mucosa during interaction with Helicobacter pylori, as determined by genetic characteristics of the bacterium and the host. Venous blood and biopsy samples of the mucosa of the antrum and body of the stomach from young patients (18 to 25 years old) were examined. The condition of the gastric mucosa was assessed using stained histological preparations. Venous blood was collected from the patients to ascertain the polymorphisms of the IL-lß and IL-IRN genes. The most pronounced changes were observed in the parameters of reparative regeneration of epithelial differentiation during colonization of the gastric mucosa by H. pylori strains carrying the CagA(+) and BabA2(+) genes. These included an increase in proliferation and apoptosis rates and alterations in epithelial differentiation markers characterized by elevated production of Shh and MUC5AC, as well as a reduction in the production of the protective mucin MUC6 by isthmus gland cells. The presence of the vacAs1 and vacAs2 genes of H. pylori results in a high level of apoptosis in epithelial cells without accelerating proliferation. It was found that after eradication, patients with preserved cellular infiltrates in their gastric mucosa plates were carriers of mainly the IL-1ß*T/IL-1RN*2R haplotypes after 12 months.

Chitosan-modified molybdenum selenide mediated efficient killing of Helicobacter pylori and treatment of gastric cancer.

Helicobacter pylori (H. pylori) is one of the major causes of gastrointestinal diseases, including gastric cancer. However, the acidic environment of the stomach and H. pylori resistance severely impair the antimicrobial efficacy of oral drugs. Here, a biocompatible chitosan-modified molybdenum selenide (MoSe2@CS) was designed for the simultaneous photothermal treatment of H. pylori infection and gastric cancer. MoSe2@CS showed a photothermal conversion efficiency was as high as 45.7 %. In the H. pylori-infected mice model, MoSe2@CS displayed a high bacteriostasis ratio of 99.9 % upon near-infrared irradiation. The antimicrobial functionality was also proved by transcriptomic sequencing study, which showed that MoSe2@CS combined with NIR laser irradiation modulated the gene expression of a variety of H. pylori bioprocesses, including cell proliferation and inflammation-related pathways. Further gut flora analysis results indicated that MoSe2@CS mediated PTT of H. pylori did not affect the homeostasis of gut flora, which highlights its advantages over traditional antibiotic therapy. In addition, MoSe2@CS exhibited a good photothermal ablation effect and significantly inhibited gastric tumor growth in vitro and in vivo. The comprehensive application of MoSe2@CS in the PTT of H. pylori infection and gastric cancer provides a new avenue for the clinical treatment of H. pylori infection and related diseases.

Determining the frequency of Helicobacter pylori in children with chronic kidney failure and its relationship to gastrointestinal symptoms.

Key Clinical Message: As there is no significant mutual relationship between Helicobacter pylori infection and chronic kidney disease in children, its routine study is not justified and is recommended only in symptomatic cases. Abstract: Children suffering from chronic kidney disease (CKD) often complain of indigestion but, if it is accompanied by abdominal pain, it is necessary to investigate and rule out Helicobacter pylori infection to confirm functional dyspepsia. Epidemiological studies in adults have conflicting results regarding the association between Helicobacter pylori infection and CKD. In this study, we determined the prevalence of H. pylori in children with kidney failure and its relationship to their gastrointestinal symptoms. In this retrospective study, 54 children with chronic kidney failure admitted to the hemodialysis ward of the Children's Medical Center, Tehran, Iran between 2012 and 2020 were studied. The mean age of our patients was 11.89 ± 3.99 years and their sex distribution was equal. H. pylori infection was reported in only three patients with 5.6%. Based on our findings, epigastric pain in children was the most common gastrointestinal symptom (70.4%). Among all patients, three patients (5.6%) died, all of them were male (P = 0.075). The most prevalent underlying cause of kidney failure in our patients was neurogenic bladder. We did not find any significant relationship between the increased risk of chronic kidney failure and co-infection with H. pylori. Investigating the cause of epigastric pain and looking for H. pylori is very important in CKD children under hemodialysis because if they receive a transplant the possibility of gastrointestinal complications will be increased with the use of steroid and immunosuppressive drugs.

Characteristics of Early Gastric Cancer in a Patient with a History of Helicobacter pylori Infection and No History of Eradication Therapy.

Objective The characteristics of gastric cancer in patients with atrophic mucosa and no apparent history of Helicobacter pylori eradication have not been thoroughly investigated. Therefore, this study examined the clinicopathological characteristics of gastric cancer in these patients. Methods We retrospectively examined the endoscopic and pathological characteristics of gastric cancer in patients who underwent endoscopic submucosal dissection. Patients or Materials We divided the patients into 2 groups: those with gastric atrophy and no history of eradication (group A; n =102) and those with a history of eradication (group B; n =161). In group A, patients were further divided into mild atrophy (group C) and severe atrophy (group D) groups, while group B was further divided into those who underwent eradication treatment >5 years ago (group E) and those who underwent eradication 1-5 years ago (group F). Results Group A comprised significantly older individuals (75±8.0 vs. 71±7.5 years old, p <0.001) with a higher frequency of elevated gastric cancer than group B (32.4% vs. 17.4%, p =0.006). Compared with group E, group A was older and had a greater incidence of elevated gastric cancer. The incidence of gastric cancer in the U or M region was lower in group C than in group D. Conclusion Gastric cancer in patients with gastric atrophy and no history of eradication was associated with an older age and higher frequency of elevated-type morphology than in those with a history of eradication.

Comprehensive multiomics analysis of the signatures of gastric mucosal bacteria and plasma metabolites across different stomach microhabitats in the development of gastric cancer.

PURPOSE: As an important component of the microenvironment, the gastric microbiota and its metabolites are associated with tumour occurrence, progression, and metastasis. However, the relationship between the gastric microbiota and the development of gastric cancer is unclear. The present study investigated the role of the gastric mucosa microbiome and metabolites as aetiological factors in gastric carcinogenesis. METHODS: Gastric biopsies from different stomach microhabitats (n = 70) were subjected to 16S rRNA gene sequencing, and blood samples (n = 95) were subjected to untargeted metabolome (gas chromatography‒mass spectrometry, GC‒MS) analyses. The datasets were analysed using various bioinformatics approaches. RESULTS: The microbiota diversity and community composition markedly changed during gastric carcinogenesis. High Helicobacter. pylori colonization modified the overall diversity and composition of the microbiota associated with gastritis and cancer in the stomach. Most importantly, analysis of the functional features of the microbiota revealed that nitrate reductase genes were significantly enriched in the tumoral microbiota, while urease-producing genes were significantly enriched in the microbiota of H. pylori-positive patients. A panel of 81 metabolites was constructed to discriminate gastric cancer patients from gastritis patients, and a panel of 15 metabolites was constructed to discriminate H. pylori-positive patients from H. pylori-negative patients. receiver operator characteristic (ROC) curve analysis identified a series of gastric microbes and plasma metabolites as potential biomarkers of gastric cancer. CONCLUSION: The present study identified a series of signatures that may play important roles in gastric carcinogenesis and have the potential to be used as biomarkers for diagnosis and for the surveillance of gastric cancer patients with minimal invasiveness.

Clinical analysis of the effect of helicobacter pylori infection on immune function in children with peptic ulcer.

Objective: To study whether children with peptic ulcer would have abnormalities in cellular and humoral immune functions, and whether Helicobacter pylori (Hp) infection would affect the immune function of children with peptic ulcer. Methods: This is a retrospective study. The subjects of study were 72 children with diagnosed and cured peptic ulcer (ulcer group), and 50 healthy children with physical examination (control group) at Baoding Hospital, Beijing Children's Hospital Affiliated to Capital Medical University from June 2020 to December 2022. Further detection was conducted on T lymphocyte subsets (CD3+, CD4+, CD8+, and CD4+/CD8+ ratio) and immunoglobulin levels. Results: Of the 72 children with peptic ulcer, 53(73.6%) were positive for Hp (Hp-positive group) and 19 (26.4%) were negative (Hp-negative group). The levels of CD3+, CD4+, and CD4+/CD8+ ratio in the control group were significantly higher than those in the ulcer group, with statistically significant difference (P<0.05); while the level of IgG in the control group was lower than that in the ulcer group, with statistically significant difference (P<0.05). Meanwhile, there were statistically significant differences in that the levels of CD3+, CD4+ and CD8+ were increased in Hp-positive group than those in Hp-negative group before treatment (P<0.05); while CD4+/CD8+ ratio was lower in the former group than that in the latter group, with statistically significant difference (P<0.05). Conclusion: Hp infection can induce the elevation of T lymphocyte subsets. The development of peptic ulcer has an intimate association with the disorder of cellular and humoral immune functions.

Research progress on Helicobacter pylori infection related neurological diseases.

Helicobacter pylori, a type of gram-negative bacterium, infects roughly half of the global population. It is strongly associated with gastrointestinal disorders like gastric cancer, peptic ulcers, and chronic gastritis. Moreover, numerous studies have linked this bacterium to various extra-gastric conditions, including hematologic, cardiovascular, and neurological issues. Specifically, research has shown that Helicobacter pylori interacts with the brain through the microbiota-gut-brain axis, thereby increasing the risk of neurological disorders. The inflammatory mediators released by Helicobacter pylori-induced chronic gastritis may disrupt the function of the blood-brain barrier by interfering with the transmission or direct action of neurotransmitters. This article examines the correlation between Helicobacter pylori and a range of conditions, such as hyperhomocysteinemia, schizophrenia, Alzheimer's disease, Parkinson's disease, ischemic stroke, multiple sclerosis, migraine, and Guillain-Barré syndrome.

Causal relationship between Helicobacter pylori infection and IgA nephropathy: a bidirectional two-sample mendelian randomization study.

IgA nephropathy (IgAN) is one of the most common primary glomerulonephritis, and serum Helicobacter pylori (H. pylori) antibody levels are increased in patients with IgA N, but the role of H. pylori infection in the pathogenesis of IgAN is unclear. In this study, we investigated whether there is a causal relationship and reverse causality between IgAN and H. pylori infection by using a bidirectional two-sample Mendelian randomization (MR) analysis. This study was estimated using inverse variance weighted (IVW), MR-Egger and weighted median methods, with the IVW method having the strongest statistical efficacy. Seven common serum H. pylori antibodies were selected as exposure factors for positive MR analysis. The results showed that there was no evidence of a causal relationship between H. pylori infection and IgAN. Reverse MR analysis showed that there was also no evidence that the occurrence of IgAN leads to an increased risk of H. pylori infection.

Biopsy-Proven Gastric Pathological Findings in Mechanically Ventilated Intensive Care Unit Patients.

Objectives Helicobacter pylori (H. pylori) is known to affect a large proportion of the world population. It plays a role in the pathogenesis of peptic ulcer (PU) and increases the likelihood of bleeding. In critically ill patients in intensive care units (ICUs), the risk of bleeding may be much higher due to many concomitant factors. The study aimed to determine the activation of H. pylori in mechanically ventilated (MV) intensive care patients and compare this with the general population. Methods This study was performed retrospectively by screening patients who underwent esophagogastroduodenoscopy and histopathological sampling in our hospital between January and June 2023. The study included 79 patients aged between 18 and 85 years. The patients were categorized into two groups: 35 patients in the ICU with mechanical ventilation (MV) support (EMV) and 44 patients who presented to the gastroenterology department due to dyspeptic symptoms and underwent endoscopy (ED). Age; sex characteristics; laboratory parameters such as hemoglobin (Hb), hematocrit (Htc), mean cellular volume (MCV), white blood cell (WBC), neutrophil, platelet, glucose, urea, creatinine, aspartate transaminase (AST), alanine transaminase (ALT), C-reactive protein (CRP), albumin, ferritin, thyroid-stimulating hormone (TSH), anti-hepatitis C virus (HCV), hepatitis B surface antigen (HBsAg), anti-HIV; and biopsy results (H. pylori positivity, intestinal metaplasia, and atrophy) were recorded. Results A total of 79 patients who underwent gastric biopsy were assessed. There were 35 patients in the EMV group and 44 patients in the ED group. There was no difference in gender and age distribution between the groups. Hb and Htc were significantly lower in EMV compared to ED (p=0.001). Hb was 9.4±1.7 g/dL in EMV and 10.8±2.1 g/dL in ED. Htc was 29.6±5.1 in EMV and 33.5±5.7 in ED. MCV, WBC, glucose, urea, AST, ALT, CRP, and ferritin values were statistically significantly higher in EMV (p<0.05). Albumin and creatinine levels were statistically significantly lower in EMV (p<0.05). There was no significant difference between the groups in terms of neutrophils, platelets, and TSH. In the EMV group, H. pylori activity was negative in 31 (88.6%) patients and positive in four (11.4%) patients. In the ED group, H. pylori activity was negative in 30 (68.2%) patients and positive in 14 (31.8%) patients. There was a statistically significant difference between the groups in terms of H. pylori positivity (p=0.032). Conclusions The prevalence of H. pylori in MV patients in the ICU is low compared to the average population. The incidence of atrophic gastritis and intestinal metaplasia is the same. The present study supports that ICU cases do not have a higher risk of gastric premalignant lesions compared to the average population.

Obesity, abdominal obesity, metabolic obesity phenotypes, and Helicobacter pylori infection: results from NHANES 1999-2000.

BACKGROUND: Recent studies on the association between Helicobacter pylori (H. pylori) infection and obesity have reported conflicting results. Therefore, the purpose of our study was to investigate the association of obesity, abdominal obesity, and metabolic obesity phenotypes with H. pylori infection. METHODS: A cross-sectional study of 1568 participants aged 20 to 85 was conducted using the National Health and Nutrition Examination Survey (NHANES) cycle 1999-2000. Logistic regression models were employed to evaluate the association of general obesity as defined by body mass index (BMI), abdominal obesity as defined by waist circumference (WC) and waist-height ratio (WHtR), and metabolic obesity phenotypes with H. pylori seropositivity. Subgroup analyses stratified by age were conducted to explore age-specific differences in this association. RESULTS: After grouping individuals according to their WHtR, the prevalence rate of WHtR ≥ 0.5 in H. pylori-seropositive participants was significantly higher than that in H. pylori-seronegative participants (79.75 vs. 68.39, P < 0.001). The prevalence of H. pylori seropositivity in non-abdominal obesity and abdominal obesity defined by WHtR was 24.97% and 31.80%, respectively (P < 0.001). In the subgroup analysis, the adjusted association between abdominal obesity, as defined by the WHtR, and H. pylori seropositivity was significant in subjects aged < 50 years (OR = 2.23; 95% CI, 1.24-4.01; P = 0.01) but not in subjects aged ≥ 50 years (OR = 0.84; 95% CI, 0.35-1.99; P = 0.66). Subjects older than 50 years old had an OR (95% CI) for metabolically healthy obesity of 0.04 (0.01-0.35) compared with the control group. H. pylori seropositivity was consistently not associated with obesity as defined by BMI. CONCLUSIONS: Abdominal obesity, as defined by the WHtR, was associated with H. pylori infection in subjects aged ≤ 50 years.

Detection of Helicobacter pylori infection in children using rapid urease and histologic methods of diagnosis.

Objective: The study aimed to detect the presence of Helicobacter pylori infection in children using two investigative methods: the rapid urease test and histological methods. It also examined the relationship between socioeconomic status and Helicobacter pylori infection. Design: This was a cross-sectional study conducted in the paediatric theatre at Korle Bu Teaching Hospital in Accra, Ghana. Participants: Children who were scheduled for upper gastrointestinal endoscopy were recruited into the study. Main outcome measures: The presence of Helicobacter pylori in gastric biopsies was measured using a rapid urease test and histology. Results: Seventy-three children aged 2 years to 16 years were seen during the period. Both tests were positive at the same time in 36 (49.3%) out of the 73 children (p<0.0001). The positivity rates for the rapid urease test and histology were 57.5% and 53.4 %, respectively. Significant predictors of the histology presence of H. pylori were a large household size of at least 6 members (AOR: 4.03; p<0.013) and the presence of pets at home (AOR: 3.23; p<0.044). Conclusions: Substantial agreement was found between the rapid urease test and histology examination of gastric biopsies for the presence of H. pylori. Children from large households and those with pets at home appear to have increased odds of having H. pylori infection of the gastric mucosa. Funding: None declared.

Exopolysaccharide from Lacticaseibacillus paracasei alleviates gastritis in Helicobacter pylori-infected mice by regulating gastric microbiota.

Introduction: Many probiotics have the ability to produce extracellular polysaccharides (EPS). EPS derived from these probiotics has been confirmed to regulate the host intestinal microecological balance and alleviate the symptoms of diseases caused by gastrointestinal microecological imbalance. Results: Lactic acid bacteria (LAB) strain with good exopolysaccharide (EPS) producing ability, namely, Lacticaseibacillus paracasei ZFM54 (L. paracasei ZFM54) was screened. The fermentation conditions of L. paracasei ZFM54 for EPS production were optimized. The EPS54 was characterized by chemical component and monosaccharide composition determination, UV, FT-IR and NMR spectra analysis. Cango red, SEM, AFM and XRD analysis were conducted to characterize the structure of EPS54. The EPS54 effectively reduced the colonization of Helicobacter pylori to AGS cells and recovered the cell morphology. EPS54 could also effectively alleviate the gastritis in the H. pylori-infected mice by down-regulating the mRNA expression levels of pro-inflammatory cytokines IL-6, IL-8, IL-1ß and TNF-α and up-regulating the mRNA expression of inflammatory cytokine IL-10 in gastric cells. EPS54 was also found to be able to positively regulate the structure of gastric microbiota. Conclusion: The EPS 54 from L. paracasei ZFM54 can alleviate gastritis in H. pylori-infected mice by modulating the gastric microbiota.

Modifiable Risk Factors in Hispanic Adults With Gastric Cancer in the United States.

BACKGROUND: Hispanics make up 19% of the U.S. population and are experiencing rising rates of cancer, primarily due to an increase in infection-related cancers (gastric, hepatic, cervical) and advanced cancers secondary to delayed screening (colorectal, cervical, breast). There is an increased incidence of gastric cancer (associated with infection, obesity, alcohol, and tobacco use) in Hispanics, especially at a young age, highlighting the need to consider ethnicity as a risk factor. METHODS: This study utilized the 2016-2019 National Inpatient Sample database to examine all patients admitted with gastric cancer. Individuals were stratified by race, age, and comorbidities, including modifiable risk factors that are associated with gastric cancer. RESULTS: There were 5,785 (7.44%) patients aged 18-44, 28,370 (36.49%) aged 45-64, and 43,590 (56.07%) over 65 years of age. Notably, 34.3% of the youngest group were Hispanic, contrasted with 19.7% and 12.9% in the older groups, respectively. Younger Hispanic patients showed a higher prevalence of H. pylori infection (8.6%) compared with older Hispanics (3.6% in the middle age group and 2.1% in the oldest, p<0.01). There was a high prevalence of obesity, tobacco use, and gastric ulcers in this cohort. Other risk factors such as alcohol use and gastric polyps were present at a lesser prevalence. CONCLUSIONS: This study reveals that Hispanic patients tend to have a younger age of onset of gastric cancer, coupled with an increased incidence of H. pylori infection at a younger age. This finding underscores the potential benefit of H. pylori screening among asymptomatic young Hispanics with the aim of reducing gastric cancer morbidity and mortality in this population.

Impact of high-altitude hypoxia on Helicobacter pylori-induced gastritis pathological manifestations and inflammatory responses.

BACKGROUND: Chronic gastritis caused by Helicobacter pylori (Hp) infection is a common gastrointestinal disorder. Despite the high prevalence of Hp infection and chronic gastritis in the Tibetan Plateau, there is a lack of studies elucidating the influence of plateau hypoxia on Hp-induced gastritis. This study aimed to investigate the impact of high-altitude hypoxia on Hp-induced gastritis, particularly focusing on pathological manifestations and inflammatory responses. METHODS: This study was conducted from July 2023 to March 2024 at the Department of Gastroenterology, Affiliated Hospital of Qinghai University. Ninety patients diagnosed with chronic gastritis were enrolled in the study and divided into four groups based on their residential altitude and Hp infection status. Data on endoscopic and pathological characteristics were collected, along with serum oxidative stress and inflammatory markers. RESULTS: Patients with Hp gastritis exhibit distinctive features in the gastric mucosa, including diffuse erythema, enlarged folds, and white turbid mucus during endoscopy. Notably, individuals with Hp gastritis at high altitudes show a higher prevalence of diffuse erythema and enlarged folds. Pathological analysis reveals that these patients have elevated gastric mucosal inflammation scores and increased chronic and active inflammation. Furthermore, individuals with Hp gastritis at high altitudes demonstrate elevated levels of serum TNF-α, IL-1ß, IL-6, and MDA, as well as reduced serum SOD and GSH-Px activities. CONCLUSIONS: High-altitude hypoxia may exacerbate gastric mucosal damage by enhancing oxidative stress and inflammatory response induced by Hp infection.

Navigating through 65 years of insights: lessons learned on functional abdominal pain in children.

In 1958, Apley and Naish authored a groundbreaking paper in Archives of Disease in Childhood, elucidating the epidemiology and risk factors of recurrent abdominal pain in children-a subject that had confounded clinicians of their time. Surprisingly, even after 65 years, there are several unanswered questions regarding the etiology, pathophysiology, and management of pediatric abdominal pain. Contrary to the prevailing notion that children naturally outgrow functional abdominal pain, compelling evidence suggests it's possible these children develop a number of clinically significant psychological issues that could profoundly impact their quality of life and, consequently, future health and educational outcomes. In this light, we aimed to comprehensively review the current literature to update the knowledge of practicing clinicians on functional abdominal pain, summarizing the evidence from the last 65 years.Conclusion: The enduring unanswered questions surrounding childhood abdominal pain continue to challenge clinicians, resulting in unnecessary investigations, thereby contributing to substantial healthcare expenditures. It is also evident that children with long-standing symptoms would progress to adulthood with the potential to develop irritable bowel syndrome and many psychological disturbances. Several key interventions using pharmacological agents, such as amitriptyline, showed that some of these drugs are no more effective than the placebo in clinical trials. Several research during the recent past suggest that psychological interventions such as gut-directed hypnotherapy alleviate symptoms and ensure better prognosis in the long run. Therefore, clinicians and researchers must join hands to explore the pathophysiological mechanisms underpinning functional abdominal pain and novel therapeutic strategies to ensure the well-being of these children. What is Known: • Functional abdominal pain disorders are common among children, with a worldwide prevalence of 13.5% of children suffering from at least one of these disorders • These disorders contribute to a significant reduction in the quality of life of affected children and their families and lead to an array of psychological problems What is New: • The biological basis of functional abdominal pain is becoming more explicit, including complex interactions between altered microbiome, deranged motility, and psychological dysfunction with gut-brain interactions • Novel approaches giving minimal emphasis on pharmacological interventions and exploring psychological interventions are showing promising results.

Indole-3-Lactic Acid Derived from Lacticaseibacillus paracasei Inhibits Helicobacter pylori Infection via Destruction of Bacteria Cells, Protection of Gastric Mucosa Epithelial Cells, and Alleviation of Inflammation.

Indole-3-lactic acid (ILA) has exhibited antimicrobial properties. However, its role in inhibiting Helicobacter pylori infection remains elusive. This study investigated the inhibitory effect of ILA produced by Lacticaseibacillus paracasei on H. pylori, which was further confirmed by cell and animal experiments. 5 mg/mL ILA was sufficient to directly inhibit the growth of H. pylori in vitro, with a urease inhibitory activity reaching 60.94 ± 1.03%, and the cell morphology and structure were destroyed. ILA inhibited 56.5% adhesion of H. pylori to GES-1 and significantly reduced the number of apoptotic cells. Furthermore, ILA suppresses H. pylori colonization by approximately 38% to 63%, reduced inflammation and oxidative stress in H. pylori-infected mice, and enhanced the enrichment and variety of gut microbiota, notably fostering the growth of beneficial bacteria such as Lactobacillus and Bifidobacterium strains. The results support that ILA derived from Lactobacillus can be applicated as a novel prebiotic in anti-H. pylori functional foods.

CemR atypical response regulator impacts energy conversion in Campylobacteria.

Campylobacter jejuni and Arcobacter butzleri are microaerobic food-borne human gastrointestinal pathogens that mainly cause diarrheal disease. These related species of the Campylobacteria class face variable atmospheric environments during infection and transmission, ranging from nearly anaerobic to aerobic conditions. Consequently, their lifestyles require that both pathogens need to adjust their metabolism and respiration to the changing oxygen concentrations of the colonization sites. Our transcriptomic and proteomic studies revealed that C. jejuni and A. butzleri, lacking a Campylobacteria-specific regulatory protein, C. jejuni Cj1608, or a homolog, A. butzleri Abu0127, are unable to reprogram tricarboxylic acid cycle or respiration pathways, respectively, to produce ATP efficiently and, in consequence, adjust growth to changing oxygen supply. We propose that these Campylobacteria energy and metabolism regulators (CemRs) are long-sought transcription factors controlling the metabolic shift related to oxygen availability, essential for these bacteria's survival and adaptation to the niches they inhabit. Besides their significant universal role in Campylobacteria, CemRs, as pleiotropic regulators, control the transcription of many genes, often specific to the species, under microaerophilic conditions and in response to oxidative stress. IMPORTANCE: C. jejuni and A. butzleri are closely related pathogens that infect the human gastrointestinal tract. In order to infect humans successfully, they need to change their metabolism as nutrient and respiratory conditions change. A regulator called CemR has been identified, which helps them adapt their metabolism to changing conditions, particularly oxygen availability in the gastrointestinal tract so that they can produce enough energy for survival and spread. Without CemR, these bacteria, as well as a related species, Helicobacter pylori, produce less energy, grow more slowly, or, in the case of C. jejuni, do not grow at all. Furthermore, CemR is a global regulator that controls the synthesis of many genes in each species, potentially allowing them to adapt to their ecological niches as well as establish infection. Therefore, the identification of CemR opens new possibilities for studying the pathogenicity of C. jejuni and A. butzleri.

Helicobacter pylori East Asian type CagA hijacks more SHIP2 by its EPIYA-D motif to potentiate the oncogenicity.

CagA is a significant oncogenic factor injected into host cells by Helicobacter pylori, which is divided into two subtypes: East Asian type (CagAE), characterized by the EPIYA-D motif, and western type (CagAW), harboring the EPIYA-C motif. CagAE has been reported to have higher carcinogenicity than CagAW, although the underlying reason is not fully understood. SHIP2 is an intracellular phosphatase that can be recruited by CagA to perturb the homeostasis of intracellular signaling pathways. In this study, we found that SHIP2 contributes to the higher oncogenicity of CagAE. Co-Immunoprecipitation and Pull-down assays showed that CagAE bind more SHIP2 than CagAW. Immunofluorescence staining showed that a higher amount of SHIP2 recruited by CagAE to the plasma membrane catalyzes the conversion of PI(3,4,5)P3 into PI(3,4)P2. This alteration causes higher activation of Akt signaling, which results in enhanced IL-8 secretion, migration, and invasion of the infected cells. SPR analysis showed that this stronger interaction between CagAE and SHIP2 stems from the higher affinity between the EPIYA-D motif of CagAE and the SH2 domain of SHIP2. Structural analysis revealed the crucial role of the Phe residue at the Y + 5 position in EPIYA-D. After mutating Phe of CagAE into Asp (the corresponding residue in the EPIYA-C motif) or Ala, the activation of downstream Akt signaling was reduced and the malignant transformation of infected cells was alleviated. These findings revealed that CagAE hijacks SHIP2 through its EPIYA-D motif to enhance its carcinogenicity, which provides a better understanding of the higher oncogenic risk of H. pylori CagAE.