Preventing and Treating Colic: An Update.

Infantile colic (IC) is c is a self-limiting functional gastrointestinal disorder (FGID) with a favorable natural history. Worldwide, IC has a significant impact on many newborns and their families. Although not an indication of an illness, its symptoms are wide and generic and may indicate a potentially serious underlying issue in a tiny percentage of newborns who may require a medical evaluation. The pathogenesis appears to be multifactorial implying a complex relationship between the infant and the environment. One of the most studied theories attributes a key role to the gut microbiota in the pathogenesis of IC. A variety of approaches have been suggested for the clinical management of IC, and several randomized controlled trials have been reported in the literature. Probiotics can change the host's microbiota and positively impact health. They may be able to restore balance and create a better intestinal microbiota landscape since there is mounting evidence that the gut microbial environment of colicky newborns differs from that of healthy infants. In this review, we revise the most commonly studied probiotics and mixtures to treat and prevent IC and the most recent recommendations.

Self-Reported Nonceliac Gluten Sensitivity in Italian Young Adults: A Cross-Sectional Study. A Dietary Fad?

INTRODUCTION: 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 nonceliac 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 13 Italian cities to investigate the dietary attitudes of more than 9,400 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 thirty-four of 9,432 eligible participants (55.5%) fully completed the questionnaire. Excluding those with previous gastrointestinal diagnoses of celiac disease and wheat allergy, we have finally analyzed 4,987 questionnaires. Four hundred 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% confidence interval 6.0-6.9), with a higher prevalence in women (79.9%). The most frequent gluten-related symptoms were bloating, abdominal pain, and tiredness. DISCUSSION: 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.

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.

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.

Infantile Colic and Long-Term Outcomes in Childhood: A Narrative Synthesis of the Evidence.

About 1 in 4 infants comes forward with prolonged crying, agitation, or infant colic (IC) during the first three months of life and is referred for medical evaluation. The pathogenesis remains poorly understood, as do its implications for future health. The aim of this narrative review was to critically examine and discuss the available literature on long-term consequences of excessive crying and/or colic. Most studies display an association between IC and the onset of functional gastrointestinal disorders (FGIDs) years later, probably related to the presence of common etiopathogenetic factors (environmental, dietary, intestinal dysmotility, visceral hypersensitivity). Although allergic disease in first-degree relatives may be a risk factor for IC, the latter does not appear to be a risk factor for subsequent atopic disease in the individual. Overall, there seems to be a relationship between IC and subsequent headaches, of the migraine type. Similarly, behavioral problems in children with a history of IC appear to be associated with higher parental stress scores. However, the current evidence is based on associations, and currently, a causal relationship between excessive crying and IC and long-term consequences remains not documented.

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.

Role of social media use in onset of functional gastrointestinal disorders in children.

The use of social media has increased considerably in recent years. However, these tools are not always used consciously, and the stress that can result from their inappropriate use is often underestimated. Children, who tend to be heavy users of social media, are exposed to risks associated with their intensive use. Data on the consequences of social media on children's health are extensive; however, few studies have examined the association between their use and functional gastrointestinal disorders (FGIDs). Our research showed that social media use is associated with adverse health outcomes such as stress, poor sleep quality, and gastrointestinal disorders in children and adolescents. FGIDs should be considered a group of biopsychosocial disorders involving gut dysfunction and psychological health. Stress may exacerbate the symptoms of these disorders and is associated with psychological comorbidities. Recent findings demonstrated a high prevalence of social media use and the incidence of psychological disorders, such as anxiety and depression, and decreased well-being in children with FGIDs. This review underlines that social media use is an emerging aspect of the psychosocial lives of children and adolescents; thus, it may be involved in FGID onset. Further studies in this field are needed to elucidate the link between social media and gastrointestinal health. Clinicians and politicians can play an important role in promoting the regulated and responsible use of digital platforms to protect the psychological health and preserve the well-being of children and adolescents.

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.

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.

Is acidemia at birth a risk factor for functional gastrointestinal disorders?

Functional gastrointestinal disorders (FGIDs) are common in early childhood. It has been demonstrated that neonatal acidemia at delivery can lead to significant neonatal morbidity. The primary aim of this study was to evaluate the relationship between acidemia at birth and the development of FGIDs, as regurgitation, colic, and constipation, in term infants. Term newborns born at the Foggia University Hospital, Italy during the year 2020 were included in the study. As per routine clinical practice, a cord blood gas analysis on a blood sample drawn from the umbilical artery (UA) of each infant immediately after birth was performed, and Apgar score was recorded. One year after birth, each infant's parents were interviewed through a phone call to investigate development of FGIDs, feeding practices, and morbidities. During the study period, 1574 term newborns met the inclusion criteria. The prevalence of infantile colic, regurgitation, and constipation was higher in infants with low UA pH (colic 51.5% vs. 25.4%, p < 0.001; regurgitation 30.6% vs. 15.2%, p < 0.001; constipation 24.6% vs. 16.0%, p = 0.015), with infants having moderate-severe acidemia facing the highest risk for all the examined FGIDs. In binary logistic regression analyses, UA pH and perinatal antibiotic exposure proved to be independently associated with the later diagnosis of each FGID. CONCLUSION: Newborns with acidemia at birth appear to face a higher risk of FGIDs in infancy. Avoiding low cord blood pH should continue to be the goal for obstetricians, while enhanced long-term surveillance for infants who experienced birth acidemia should be required. WHAT IS KNOWN: • Cord blood gas analysis is recommended in all high-risk deliveries, and in some centers, it is performed after all deliveries. • Neonatal acidemia at birth has been linked to adverse outcomes, mainly neurological. Recently, perinatal asphyxia has been reported to increase the risk of developing necrotizing enterocolitis in term infants. WHAT IS NEW: • An association between acidemia at birth and risk of developing FGIDs such as regurgitation and colic during the first year of life had never been described so far. • An increased surveillance of infants with low UA pH at birth may be beneficial and could allow for early detection of any of the reported FGIDs.

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.

Iodine Absorption in Celiac Children: A Longitudinal Pilot Study.

Background: non-autoimmune thyroid disorder is a common finding in celiac patients, more frequent than in the general population. An impairment of iodine absorption has been hypothesized, but it has never been investigated so far. We aimed to evaluate the iodine absorption in children and adolescents with newly diagnosed celiac disease. Methods: 36 consecutive celiac patients (age 7.4 years, range 2.4-14.5 years) before starting a gluten-free diet (GFD) were enrolled. We assayed the urinary iodine concentration (UIC) in a 24-h urine sample, at baseline (T0) after 3 (T1) and 12 months (T2) of GFD. Results: UIC at T0 was 64 µg/L (IQR 45-93.25 µg/L) with an iodine deficiency rate of 77.8%. UIC was not different according to histological damage, clinical presentation (typical vs atypical); we found no correlation with the thyroid function tests and auxological parameters. UIC was not statistically different at T1 (76 µg/L) and T2 (89 µg/L) vs T0. UIC at T2 was similar between patients with positive and negative anti-transglutaminase antibodies at T2. No patients presented overt hypothyroidism during the study. Conclusions: We found that iodine absorption in celiac children is impaired compared to the general population; it increases slightly, but not significantly, during the GFD. We should regularly reinforce the need for a proper iodine intake in celiac disease patients to reduce iodine deficiency risk.

Anti-Inflammatory and Immunomodulatory Effects of Probiotics in Gut Inflammation: A Door to the Body.

Hosting millions of microorganisms, the digestive tract is the primary and most important part of bacterial colonization. On one side, in cases of opportunistic invasion, the abundant bacterial population inside intestinal tissues may face potential health problems such as inflammation and infections. Therefore, the immune system has evolved to sustain the host-microbiota symbiotic relationship. On the other hand, to maintain host immune homeostasis, the intestinal microflora often exerts an immunoregulatory function that cannot be ignored. A field of great interest is the association of either microbiota or probiotics with the immune system concerning clinical uses. This microbial community regulates some of the host's metabolic and physiological functions and drives early-life immune system maturation, contributing to their homeostasis throughout life. Changes in gut microbiota can occur through modification in function, composition (dysbiosis), or microbiota-host interplays. Studies on animals and humans show that probiotics can have a pivotal effect on the modulation of immune and inflammatory mechanisms; however, the precise mechanisms have not yet been well defined. Diet, age, BMI (body mass index), medications, and stress may confound the benefits of probiotic intake. In addition to host gut functions (permeability and physiology), all these agents have profound implications for the gut microbiome composition. The use of probiotics could improve the gut microbial population, increase mucus-secretion, and prevent the destruction of tight junction proteins by decreasing the number of lipopolysaccharides (LPSs). When LPS binds endothelial cells to toll-like receptors (TLR 2, 4), dendritic cells and macrophage cells are activated, and inflammatory markers are increased. Furthermore, a decrease in gut dysbiosis and intestinal leakage after probiotic therapy may minimize the development of inflammatory biomarkers and blunt unnecessary activation of the immune system. In turn, probiotics improve the differentiation of T-cells against Th2 and development of Th2 cytokines such as IL-4 and IL-10. The present narrative review explores the interactions between gut microflora/probiotics and the immune system starting from the general perspective of a biological plausibility to get to the in vitro and in vivo demonstrations of a probiotic-based approach up to the possible uses for novel therapeutic strategies.

Retrospective Study on Breastfeeding Practices by SARS-COV-2 Positive Mothers in a High Risk Area for Coronavirus Infection.

BACKGROUND: During the pandemic of SARS-Cov-2, among other clinical and public health issues, a major concern raised by SARS-CoV-2 is the possibility of transmission of the infection from mother to child in the perinatal period. This has placed a question mark on the safety of breastfeeding, with ambiguity on the joint management of SARS-CoV-2 positive or suspected mothers and their children. It was aimed to evaluate breastfeeding rates for newborns of asymptomatic SARS-CoV-2 positive mothers who were temporarily separated from their babies at birth, compared to those who were not separated. RESULTS: Babies who were not isolated from their mothers at delivery were significantly more likely to be breastfed and were at no higher risk of infection with SARS-CoV-2. CONCLUSION: Following the World Health Organization (WHO) recommendations and strict hand and mask hygiene measures, breastfeeding practices can be established and maintained through rooming-in, thus promoting the mother-child bond without compromising the safety of the newborn.