Celiac Disease: The Importance of Studying the Duodenal Mucosa-Associated Microbiota.

There is increasing evidence indicating that changes in both the composition and functionality of the intestinal microbiome are closely associated with the development of several chronic inflammatory diseases, with celiac disease (CeD) being particularly noteworthy. Thanks to the advent of culture-independent methodologies, the ability to identify and quantify the diverse microbial communities residing within the human body has been significantly improved. However, in the context of CeD, a notable challenge lies in characterizing the specific microbiota present on the mucosal surfaces of the intestine, rather than relying solely on fecal samples, which may not fully represent the relevant microbial populations. Currently, our comprehension of the composition and functional importance of mucosa-associated microbiota (MAM) in CeD remains an ongoing field of research because the limited number of available studies have reported few and sometimes contradictory results. MAM plays a crucial role in the development and progression of CeD, potentially acting as both a trigger and modulator of the immune response within the intestinal mucosa, given its proximity to the epithelial cells and direct interaction. According to this background, this review aims to consolidate the existing literature specifically focused on MAM in CeD. By elucidating the complex interplay between the host immune system and the gut microbiota, we aim to pave the way for new interventions based on novel therapeutic targets and diagnostic biomarkers for MAM in CeD.

SELF-REPORTED NON-CELIAC GLUTEN SENSITIVITY IN ITALIAN YOUNG ADULTS: A CROSS-SECTIONAL STUDY. A DIETARY FAD?

OBJECTIVES: In different countries, the exact prevalence of people that refer symptoms after gluten ingestion is increasing and the unavailability of reliable laboratory tests to diagnose the condition known as non-celiac gluten sensitivity (NCGS) has opened the door to the spread of survey-based studies to hypothesize a prevalence of this condition with highly discordant results. We aim to describe the attitude toward gluten consumption in a large population of young adults in Italy. METHODS: A questionnaire-based cross-sectional study was conducted in thirteen Italian cities to investigate the dietary attitudes of more than 9400 people distributed throughout the country about gluten consumption. Only those referring to gluten-related symptoms with a frequency equal to "always" or "most of the time" were considered self-reported NCGS (SR-NCGS) patients. RESULTS: Five thousand two hundred and thirty-four of 9432 eligible participants (55.5%) fully completed the questionnaire. Excluding those with previous gastrointestinal diagnoses of celiac disease and wheat allergy, we have finally analyzed 4987 questionnaires. Four hundred and eighty-seven participants indicated gluten-related symptoms "always" or "most of the time" (SR-NCGS subjects), while 121 already had a medical diagnosis of NCGS. The minimum prevalence figure of SR-NCGS is 6.4% (95%CI: 6.0-6.9), with a higher prevalence in females (79.9%). The most frequent gluten-related symptoms were bloating, abdominal pain and tiredness. CONCLUSIONS: The high prevalence of people reporting symptoms after gluten ingestion requires that the diagnosis of NCGS should be ascertained with a double-blind controlled study to limit the number of people who improperly approach a gluten-free diet.

Mucoadhesive Budesonide Solution for the Treatment of Pediatric Eosinophilic Esophagitis.

Eosinophilic Esophagitis is an antigen-mediated inflammatory disease characterized by thickening of the esophageal wall, leading to dysphagia, vomiting, reflux, and abdominal pain. This disease can be treated with a therapeutic approach ranging from diet to pharmacological therapy. Jorveza® (budesonide) and Dupixent® (dupilumab) are treatments for Eosinophilic Esophagitis approved by the European Medicines Agency in adults but not in children. Budesonide-based extemporaneous oral liquid suspensions could be prepared for pediatric use. The main limit of this formulation is that budesonide needs a longer residence time on the esophageal mucosa to solubilize and diffuse in it to exert its local anti-inflammatory effect. Herein, we propose the development of an extemporaneous mucoadhesive oral budesonide solution for the pediatric population. A liquid vehicle containing hydroxypropyl-beta-cyclodextrin as a complexing agent and carboxymethylcellulose sodium as a mucoadhesive excipient was used to prepare budesonide-based formulations. A stable solution at a concentration of 0.7 mg/mL was successfully prepared and characterized. The formulation showed rheological and mucoadhesive properties suitable for an Eosinophilic Esophagitis local prolonged treatment. In this way, pharmacists can prepare stable budesonide-based mucoadhesive solutions, providing both patients and physicians with a new therapeutic option for Eosinophilic Esophagitis pediatric treatment.

Diagnostic Delay of Celiac Disease in Childhood.

Importance: The extent and factors associated with risk of diagnostic delay in pediatric celiac disease (CD) are poorly understood. Objectives: To investigate the diagnostic delay of CD in childhood, and to assess factors associated with this delay. Design, Setting, and Participants: Multicenter, retrospective, cross-sectional study (2010-2019) of pediatric (aged 0-18 years) patients with CD from 13 pediatric tertiary referral centers in Italy. Data were analyzed from January to June 2023. Main Outcomes and Measures: The overall diagnostic delay (ie, the time lapse occurring from the first symptoms or clinical data indicative of CD and the definitive diagnosis), further split into preconsultation and postconsultation diagnostic delay, were described. Univariable and multivariable linear regression models for factors associated with diagnostic delay were fitted. Factors associated with extreme diagnostic delay (ie, 1.5 × 75th percentile) and misdiagnosis were assessed. Results: A total of 3171 patients with CD were included. The mean (SD) age was 6.2 (3.9) years; 2010 patients (63.4%) were female; and 10 patients (0.3%) were Asian, 41 (1.3%) were Northern African, and 3115 (98.3%) were White. The median (IQR) overall diagnostic delay was 5 (2-11) months, and preconsultation and postconsultation diagnostic delay were 2 (0-6) months and 1 (0-3) month, respectively. The median (IQR) extreme overall diagnostic delay (586 cases [18.5%]) was 11 (5-131) months, and the preconsultation and postconsultation delays were 6 (2-120) and 3 (1-131) months, respectively. Patients who had a first diagnosis when aged less than 3 years (650 patients [20.5%]) showed a shorter diagnostic delay, both overall (median [IQR], 4 [1-7] months for patients aged less than 3 years vs 5 [2-12] months for others) and postconsultation (median [IQR], 1 [0-2] month for patients aged less than 3 years vs 2 [0-4] months for others). A shorter delay was registered in male patients, both overall (median [IQR], 4 [1-10] months for male patients vs 5 [2-12] months for female patients) and preconsultation (median [IQR], 1 [0-6] month for male patients vs 2 [0-6] months for female patients). Family history of CD was associated with lower preconsultation delay (odds ratio [OR], 0.59; 95% CI, 0.47-0.74) and lower overall extreme diagnostic delay (OR, 0.75; 95% CI, 0.56-0.99). Neurological symptoms (78 patients [21.5%]; OR, 1.35; 95% CI, 1.03-1.78), gastroesophageal reflux (9 patients [28.1%]; OR, 1.87; 95% CI, 1.02-3.42), and failure to thrive (215 patients [22.6%]; OR, 1.62; 95% CI, 1.31-2.00) showed a more frequent extreme diagnostic delay. A previous misdiagnosis (124 patients [4.0%]) was more frequently associated with gastroesophageal reflux disease, diarrhea, bloating, abdominal pain, constipation, fatigue, osteopenia, and villous atrophy (Marsh 3 classification). Conclusions and Relevance: In this cross-sectional study of pediatric CD, the diagnostic delay was rather short. Some factors associated with risk for longer diagnostic delay and misdiagnosis emerged, and these should be addressed in future studies.

Novel Bacteroides Vulgatus strain protects against gluten-induced break of human celiac gut epithelial homeostasis: a pre-clinical proof-of-concept study.

BACKGROUND AND AIMS: We have identified a decreased abundance of microbial species known to have a potential anti-inflammatory, protective effect in subjects that developed Celiac Disease (CeD) compared to those who did not. We aim to confirm the potential protective role of one of these species, namely Bacteroides vulgatus, and to mechanistically establish the effect of bacterial bioproducts on gluten-dependent changes on human gut epithelial functions. METHODS: We identified, isolated, cultivated, and sequenced a unique novel strain (20220303-A2) of B. vulgatus found only in control subjects. Using a human gut organoid system developed from pre-celiac patients, we monitored epithelial phenotype and innate immune cytokines at baseline, after exposure to gliadin, or gliadin plus B. vulgatus cell free supernatant (CFS). RESULTS: Following gliadin exposure, we observed increases in epithelial cell death, epithelial monolayer permeability, and secretion of pro-inflammatory cytokines. These effects were mitigated upon exposure to B. vulgatus 20220303-A2 CFS, which had matched phenotype gene product mutations. These protective effects were mediated by epigenetic reprogramming of the organoids treated with B. vulgatus CFS. CONCLUSIONS: We identified a unique strain of B. vulgatus that may exert a beneficial role by protecting CeD epithelium against a gluten-induced break of epithelial tolerance through miRNA reprogramming. IMPACT: Gut dysbiosis precedes the onset of celiac disease in genetically at-risk infants. This dysbiosis is characterized by the loss of protective bacterial strains in those children who will go on to develop celiac disease. The paper reports the mechanism by which one of these protective strains, B. vulgatus, ameliorates the gluten-induced break of gut epithelial homeostasis by epigenetically re-programming the target intestinal epithelium involving pathways controlling permeability, immune response, and cell turnover.

Gastrointestinal involvement in STEC-associated hemolytic uremic syndrome: 10 years in a pediatric center.

BACKGROUND: The gastrointestinal (GI) tract represents one of the main targets of typical hemolytic uremic syndrome (HUS) in children. In this observational study, we tried to establish (1) the main features of GI complications during STEC-HUS and (2) the relationship between Escherichia coli serotypes and Shiga toxin (Stx) variants with hepatopancreatic involvement. METHODS: A total of 79 STEC-HUS patients were admitted to our pediatric nephrology department between January 2012 and June 2021. Evidence of intestinal, hepatobiliary, and pancreatic involvements was reported for each patient, alongside demographic, clinical, and laboratory features. Frequency of gastrointestinal complications across groups of patients infected by specific E. coli serotypes and Stx gene variants was evaluated. RESULTS: Six patients developed a bowel complication: two developed rectal prolapse, and four developed bowel perforation which resulted in death for three of them and in bowel stenosis in one patient. Acute pancreatitis was diagnosed in 13 patients. An isolated increase in pancreatic enzymes and/or liver transaminases was observed in 41 and 15 patients, respectively. Biliary sludge was detected in three, cholelithiasis in one. Forty-seven patients developed direct hyperbilirubinemia. Neither E. coli serotypes nor Shiga toxin variants correlated with hepatic or pancreatic involvement. CONCLUSIONS: During STEC-HUS, GI complications are common, ranging from self-limited elevation of laboratory markers to bowel perforation, a severe complication with a relevant impact on morbidity and mortality. Hepatopancreatic involvement is frequent, but usually short-lasting and self-limiting.

Precision microbial intervention improves social behavior but not autism severity: A pilot double-blind randomized placebo-controlled trial.

Autism spectrum disorder (ASD) is characterized by the presence of restricted/repetitive behaviors and social communication deficits. Because effective treatments for ASD remain elusive, novel therapeutic strategies are necessary. Preclinical studies show that L. reuteri selectively reversed social deficits in several models for ASD. Here, in a double-blind, randomized, placebo-controlled trial, we tested the effect of L. reuteri (a product containing a combination of strains ATCC-PTA-6475 and DSM-17938) in children with ASD. The treatment does not alter overall autism severity, restricted/repetitive behaviors, the microbiome composition, or the immune profile. However, L. reuteri combination yields significant improvements in social functioning that generalized across different measures. Interestingly, ATCC-PTA-6475, but not the parental strain of DSM-17938, reverses the social deficits in a preclinical mouse model for ASD. Collectively, our findings show that L. reuteri enhances social behavior in children with ASD, thereby warranting larger trials in which strain-specific effects should also be investigated.

Gut Immunobiosis and Biomodulators.

The human gastrointestinal (GI) tract hosts complex and dynamic populations of microorganisms (gut microbiota) in advantageous symbiosis with the host organism through sophisticated molecular cross-talk. The balance and diversification within microbial communities (eubiosis) are crucial for the immune and metabolic homeostasis of the host, as well as for inhibiting pathogen penetration. In contrast, compositional dysregulation of the microbiota (dysbiosis) is blamed for the determinism of numerous diseases. Although further advances in the so-called 'omics' disciplines are needed, dietary manipulation of the gut microbial ecosystem through biomodulators (prebiotics, probiotics, symbionts, and postbiotics) represents an intriguing target to stabilize and/or restore eubiosis. Recently, new approaches have been developed for the production of infant formulas supplemented with prebiotics (human milk oligosaccharides [HMOs], galacto-oligosaccharides [GOS], fructo-oligosaccharides [FOS]), probiotics, and postbiotics to obtain formulas that are nutritionally and biologically equivalent to human milk (closer to the reference).

Intestinal Barrier Dysfunction and Microbiota-Gut-Brain Axis: Possible Implications in the Pathogenesis and Treatment of Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with multifactorial etiology, characterized by impairment in two main functional areas: (1) communication and social interactions, and (2) skills, interests and activities. ASD patients often suffer from gastrointestinal symptoms associated with dysbiotic states and a "leaky gut." A key role in the pathogenesis of ASD has been attributed to the gut microbiota, as it influences central nervous system development and neuropsychological and gastrointestinal homeostasis through the microbiota-gut-brain axis. A state of dysbiosis with a reduction in the Bacteroidetes/Firmicutes ratio and Bacteroidetes level and other imbalances is common in ASD. In recent decades, many authors have tried to study and identify the microbial signature of ASD through in vivo and ex vivo studies. In this regard, the advent of metabolomics has also been of great help. Based on these data, several therapeutic strategies, primarily the use of probiotics, are investigated to improve the symptoms of ASD through the modulation of the microbiota. However, although the results are promising, the heterogeneity of the studies precludes concrete evidence. The aim of this review is to explore the role of intestinal barrier dysfunction, the gut-brain axis and microbiota alterations in ASD and the possible role of probiotic supplementation in these patients.

Early Antibody Dynamics in a Prospective Cohort of Children At Risk of Celiac Disease.

INTRODUCTION: The purpose of this study was to identify possible serum biomarkers predicting celiac disease (CD) onset in children at risk. METHODS: A subgroup from an ongoing, international prospective study of children at risk of CD was classified according to an early trajectory of deamidated gliadin peptides (DGPs) immunoglobulin (Ig) G and clinical outcomes (CD, potential CD, and CD autoimmunity). RESULTS: Thirty-eight of 325 children developed anti-tissue transglutaminase IgA antibody (anti-tTG IgA) seroconversion. Twenty-eight of 38 children (73.6%) showed an increase in anti-DGPs IgG before their first anti-tTG IgA seroconversion. DISCUSSION: Anti-DGPs IgG can represent an early preclinical biomarker predicting CD onset in children at risk.

Prevalence and detection rate of celiac disease in Italy: Results of a SIGENP multicenter screening in school-age children.

BACKGROUND: Celiac disease is a common lifelong disorder. Recent studies indicate that the number of clinically detected cases has increased over the last decades, however little is known about changes in the prevalence and the detection rate of celiac disease. AIM: To evaluate the current prevalence and detection rate of celiac disease in Italy by a multicenter, mass screening study on a large sample of school-age children. METHODS: children aged 5-11 years were screened at school by HLA-DQ2 and -DQ8 determination on a drop of blood in six Italian cities; total serum IgA and IgA anti-transglutaminase were determined in children showing HLA-DQ2 and/or -DQ8 positivity. Diagnosis of celiac disease was confirmed according to the European guidelines. RESULTS: 5994 children were eligible, 4438 participated and 1873 showed predisposing haplotypes (42.2%, 95% CI=40.7-43.7). The overall prevalence of celiac disease was 1.65% (95% CI, 1.34%-2.01%). Only 40% of celiac children had been diagnosed prior to the school screening. Symptoms evoking celiac disease were as common in celiac children as in controls. CONCLUSION: In this multicenter study the prevalence of celiac disease in school-age Italian children was one of the highest in the world. Determination of HLA predisposing genotypes is an easy and fast first-level screening test for celiac disease. Without a mass screening strategy, 60% of celiac patients remain currently undiagnosed in Italy.

Risk of obesity during a gluten-free diet in pediatric and adult patients with celiac disease: a systematic review with meta-analysis.

CONTEXT: Obesity is a significant risk factor for many pathological conditions. Whether a gluten-free diet (GFD) is a risk factor for overweight or obesity remains controversial. OBJECTIVE: The primary aim of this study was to assess the prevalence of body mass index (BMI) categories at disease presentation and the variation in BMI category from underweight/normal to overweight/obese and vice versa during a GFD. DATA SOURCES: PubMed, Scopus, and Web of Science databases were searched through February 2021 for retrospective, cross-sectional, and prospective studies reporting BMI categories at disease diagnosis and during a GFD. DATA EXTRACTION: Data were extracted by 2 reviewers independently. Disagreements were resolved by consensus; a third reviewer was consulted, if necessary. Risk of bias was assessed with the Cochrane ROBINS-I tool. DATA ANALYSIS: Subgroup analysis based on age (pediatric/adult patients), study design (prospective, cross-sectional, retrospective), and duration of GFD was performed.. Forty-five studies were selected (7959 patients with celiac disease and 20 524 healthy controls). The mean BMI of celiac patients at presentation was significantly lower than that of controls (P < 0.001). During a GFD, the mean BMI increased significantly (mean difference = 1.14 kg/m2 [95%CI, 0.68-1.60 kg/m2]; I2 = 82.8%; P < 0.001), but only 9% of patients (95%CI, 7%-12%; I2 = 80.0%) changed from the underweight/normal BMI category to the overweight/obese category, while 20% (95%CI, 11%-29%; I2 = 85.8%) moved into a lower BMI category. CONCLUSION: Most celiac patients had a normal BMI at presentation, although the mean BMI was significantly lower than that of controls. A GFD does not increase the risk of becoming overweight/obese, especially in children. The quality of several studies was suboptimal, with moderate or high overall risk of bias and heterogeneity.

Probiotics and gastrointestinal diseases.

During the past decades, scientists have discovered the intimate role of the gut microbiome in human health, and since then, several papers have been published to investigate if the use of biotics (probiotics, prebiotics, synbiotics, and postbiotics) may have a beneficial impact on human health both in treatment and prevention. We now ask ourselves whether we have reached the finish line or just a new starting point, as the evidence supporting the use of biotics in several conditions still needs a lot of work. Many questions remain unanswered today because the evidence differs depending on the indication, used strain, and amount and duration of administration. Herein we will summarize the evidence on probiotics in some gastrointestinal diseases such as infantile colic, functional abdominal pain disorders, celiac disease, acute gastroenteritis, inflammatory bowel disease, and Helicobacter pylori infection.

Case report: Late-onset hypertrophic pyloric stenosis in a 3-year-old boy: It is never too late.

Hypertrophic Pyloric Stenosis (HPS) represents a relatively rare occurrence beyond infancy. Here, we present the case of a barely 3-year-old boy diagnosed with late-onset HPS and successfully treated with extra-mucosal pyloromyotomy. We review the literature, challenging the principle that more aggressive surgical approaches should be preferred over less invasive ones.

Nutritional Assessment of Baby Food Available in Italy.

Adequate complementary feeding practices are important for short- and long-term child health. In industrialized countries, the formulation of several commercial baby foods (CBFs) and an increase in their consumption has been noticed. AIM: To update and analyze the nutritional composition of CBFs available in the Italian market. METHODS: Data collection carried out in two steps (July 2018-January 2019) and updated in May-September 2021. The information on CBFs was taken from the websites of the major CBF producers available in Italy. The collected information were: Suggested initial and final age of consumption; Ingredients; Energy value; Macronutrients (protein, lipids, and carbohydrates); Fiber; Micronutrients (sodium, iron, and calcium); Presence of salt and added sugars, flavorings, and other additives. RESULTS: Time-space for which CBFs are recommended starts too early and ends too late; protein content is adequate and even too high in some food; Amount of fats and their quality must be improved, keeping the intake of saturated fats low; Sugar content is too high in too many CBFs and salt is unnecessarily present in some of them. Finally, the texture of too many products is purée, and its use is recommended for too long, hindering the development of infants' chewing abilities.

Alterations of the Intestinal Permeability are Reflected by Changes in the Urine Metabolome of Young Autistic Children: Preliminary Results.

Several metabolomics-based studies have provided evidence that autistic subjects might share metabolic abnormalities with gut microbiota dysbiosis and alterations in gut mucosal permeability. Our aims were to explore the most relevant metabolic perturbations in a group of autistic children, compared with their healthy siblings, and to investigate whether the increased intestinal permeability may be mirrored by specific metabolic perturbations. We enrolled 13 autistic children and 14 unaffected siblings aged 2-12 years; the evaluation of the intestinal permeability was estimated by the lactulose:mannitol test. The urine metabolome was investigated by proton nuclear magnetic resonance (1H-NMR) spectroscopy. The lactulose:mannitol test unveiled two autistic children with altered intestinal permeability. Nine metabolites significantly discriminated the urine metabolome of autistic children from that of their unaffected siblings; however, in the autistic children with increased permeability, four additional metabolites-namely, fucose, phenylacetylglycine, nicotinurate, and 1-methyl-nicotinamide, strongly discriminated their urine metabolome from that of the remaining autistic children. Our preliminary data suggest the presence of a specific urine metabolic profile associated with the increase in intestinal permeability.

Twelve Months with COVID-19: What Gastroenterologists Need to Know.

Corona virus disease-19 (COVID-19) is the latest global pandemic. COVID-19 is mainly transmitted through respiratory droplets and, apart from respiratory symptoms, patients often present with gastrointestinal symptoms and liver involvement. Given the high percentage of COVID-19 patients that present with gastrointestinal symptoms (GIS), in this review, we report a practical up-to-date reference for the physician in their clinical practice with patients affected by chronic gastrointestinal (GI) diseases (inflammatory bowel disease, coeliac disease, chronic liver disease) at the time of COVID-19. First, we summarised data on the origin and pathogenetic mechanism of SARS-CoV-2. Then, we performed a literature search up to December 2020 examining clinical manifestations of GI involvement. Next, we illustrated and summarised the most recent guidelines on how to adhere to GI procedures (endoscopy, liver biopsy, faecal transplantation), maintaining social distance and how to deal with immunosuppressive treatment. Finally, we focussed on some special conditions such as faecal-oral transmission and gut microbiota. The rapid accumulation of information relating to this condition makes it particularly essential to revise the literature to take account of the most recent publications for medical consultation and patient care.

Esophageal Eosinophilia and Eosinophilic Esophagitis in Celiac Children: A Ten Year Prospective Observational Study.

The association between eosinophilic esophagitis and celiac disease is still controversial and its prevalence is highly variable. We aimed to investigate the prevalence of esophageal eosinophilia and eosinophilic esophagitis in a large group of children with celiac disease, prospectively followed over 11 years. METHODS: Prospective observational study performed between 2008 and 2019. Celiac disease diagnosis was based on ESPGHAN criteria. At least four esophageal biopsies were sampled in patients who underwent endoscopy. The presence of at least 15 eosinophils/HPF on esophageal biopsies was considered suggestive of esophageal eosinophilia; at the same time, eosinophilic esophagitis was diagnosed according to the International Consensus Diagnostic Criteria for Eosinophilic Esophagitis. RESULTS: A total of 465 children (M 42% mean age 7.1 years (range: 1-16)) were diagnosed with celiac disease. Three hundred and seventy patients underwent endoscopy, and esophageal biopsies were available in 313. The prevalence of esophageal eosinophilia in children with celiac disease was 1.6% (95% CI: 0.54-2.9%). Only one child was diagnosed as eosinophilic esophagitis; we calculated a prevalence of 0.3% (95% CI: 0.2-0.5%). The odds ratio for an association between eosinophilic esophagitis and celiac disease was at least 6.5 times higher (95% CI: 0.89-47.7%; p = 0.06) than in the general population. CONCLUSION: The finding of an increased number of eosinophils (>15/HPF) in celiac patients does not have a clinical implication or warrant intervention, and therefore we do not recommend routine esophageal biopsies unless clinically indicated.

Limosilactobacillus reuteri Strains as Adjuvants in the Management of Helicobacter pylori Infection.

Helicobacter pylori (HP) is a Gram-negative bacterium which finds its suitable habitat in the stomach. The infection affects about half of the global population with high variability in prevalence among regions and for age. HP is the main causative agent of chronic active gastritis, peptic and duodenal ulcers, and may be the primary cause of gastric cancer or MALT lymphoma. Due to the high rate of failure of eradication therapy in various countries and the increase in antibiotic resistance reported in the literature, there is an ever wider need to seek alternative therapeutic treatments. Probiotics seem to be a promising solution. In particular, the Limosilactobacillus reuteri (L. reuteri) species is a Gram-positive bacterium and is commonly found in the microbiota of mammals. L. reuteri is able to survive the gastric acid environment and bile and to colonize the gastric mucosa. This species is able to inhibit the growth of several pathogenic bacteria through different mechanisms, keeping the homeostasis of the microbiota. In particular, it is able to secrete reuterin and reutericycline, substances that exhibit antimicrobial properties, among other molecules. Through the secretion of these and the formation of the biofilm, it has been found to strongly inhibit the growth of HP and, at higher concentrations, to kill it. Moreover, it reduces the expression of HP virulence factors. In clinical trials, L. reuteri has been shown to decrease HP load when used as a single treatment, but has not achieved statistical significance in curing infected patients. As an adjuvant of standard regimens with antibiotics and pump inhibitors, L. reuteri can be used not only to improve cure rates, but especially to decrease gastrointestinal symptoms, which are a common cause of lack of compliance and interruption of therapy, leading to new antibiotic resistance.