Search Results (13)

Aging is associated with structural and functional changes in the gastrointestinal tract; however, its impact on gastric secretion remains unclear. This scoping review examines whether gastric secretion declines with age and explores its clinical implications. Following the PRISMA guidelines, PubMed, Web of Science, Embase, and Google Scholar were systematically searched from inception to December 2024. Fifteen studies (both animal and human) met the inclusion criteria: they were written in English, directly relevant to aging and gastric secretion, and had a clearly stated methodology. Evidence strength was assessed using the GRADE framework, revealing predominantly low to moderate certainty due to small sample sizes and observational study designs. Animal studies have demonstrated reduced acid secretion in older rats, which is attributed to mucosal atrophy and diminished responsiveness to gastrin. Recent human studies suggest that aging does not directly reduce acid output, as reduced acid secretion may result from a higher prevalence of atrophic gastritis, Helicobacter pylori infection, and the widespread use of proton pump inhibitors. Antisecretory therapy may lack benefits in older adult patients with hypochlorhydria/achlorhydria and increase the risk of adverse effects. Pepsin output declines with aging due to reduced chief cell function, although its clinical impact on digestion is unclear. Since intrinsic factor secretion far exceeds the amount necessary for its physiological function, even low amounts seem to be sufficient to prevent cobalamin deficiency. Age-related decline in gastric secretion is mostly attributed to age-associated disorders; however, impairment of secretory function in older people is frequent. Future research should prioritise longitudinal studies, larger cohorts, and histology-stratified analysis. Full article

Food cobalamin malabsorption (FCM) represents a prevalent, often underdiagnosed, etiology of vitamin B12 deficiency, particularly within an aging population. Unlike pernicious anemia, an autoimmune disorder targeting intrinsic factor, FCM stems from the impaired release of cobalamin from food proteins, primarily due to age-related gastric changes, medication-induced gastric hypochlorhydria, metformin, or non-immune atrophic gastritis. The clinical presentation of FCM mirrors that of general cobalamin deficiency, encompassing a spectrum of neurological (peripheral neuropathy, cognitive decline), hematological (megaloblastic anemia), and gastrointestinal (glossitis, anorexia) manifestations. Given the potential for irreversible neurological sequelae, early detection and intervention are paramount. High-dose oral cobalamin (125–250 mcg daily) has demonstrated efficacy, offering a convenient and cost-effective alternative to parenteral administration. Full article

Gastrointestinal disorders dysregulate the biochemical environment of the gastrointestinal tract by altering pH conditions during the gastric phase of digestion or by reducing the secretion of pancreatin during the intestinal part of the process. Ingested functional food could therefore lose some of its health-promoting potential apart from its nutritional value. In this work, we aimed to manufacture bread marked by decreased gluten content, using a commercial or laboratory sourdough, that could be appropriate for patients afflicted with wheat allergy, hypertension and pancreatic malfunctions. A reference sample (no sourdough) was prepared alongside wheat and wheat–rye bread samples—produced with either commercial or laboratory sourdough (L. plantarum BS, L. brevis 1269, L. sanfranciscensis 20663). We measured the QQQPP allergen content (ELISA) in bread extracts digested in vitro and determined how these extracted components affect the level of active angiotensin and alpha amylase (spectrophotometry). We then elucidated how these properties changed when physiological digestion conditions (pH and pancreatin activity) were disturbed to mimic gastric hyperacidity, hypochlorhydria or exocrine pancreatic insufficiency. The key finding was that every tested type of bread produced with laboratory sourdough exhibited pronounced angiotensin-converting enzyme inhibition. The effect was preserved even in dysregulated digestive conditions. The use of laboratory sourdough prevented an increase in allergenicity when pancreatin was restricted as opposed to the commercial sourdough, which surpassed the reference sample reading at 50% pancreatin. No statistically consistent link was reported when the inhibition of alpha amylase was assayed. In conclusion, functional bread manufactured with sourdough composed of L. plantarum BS, L. brevis 1269, and L. sanfranciscensis 20663 was shown to be potentially capable of contributing to the treatment against hypertension as evidenced by in vitro research. It was also moderately safer with regard to its allergenicity. Full article

Autoimmune atrophic gastritis is an immune-mediated disease resulting in autoimmune destruction of the specialized acid-producing gastric parietal cells. As a consequence, in autoimmune atrophic gastritis, gastric acid secretion is irreversibly impaired, and the resulting hypochlorhydria leads to the main clinical manifestations and is linked, directly or indirectly, to the long-term neoplastic complications of this disease. In the last few years, autoimmune atrophic gastritis has gained growing interest leading to the acquisition of new knowledge on different aspects of this disorder. Although reliable serological biomarkers are available and gastrointestinal endoscopy techniques have substantially evolved, the diagnosis of autoimmune atrophic gastritis is still affected by a considerable delay and relies on histopathological assessment of gastric biopsies. One of the reasons for the diagnostic delay is that the clinical presentations of autoimmune atrophic gastritis giving rise to clinical suspicion are very different, ranging from hematological to neurological–psychiatric up to gastrointestinal and less commonly to gynecological–obstetric symptoms or signs. Therefore, patients with autoimmune atrophic gastritis often seek advice from physicians of other medical specialties than gastroenterologists, thus underlining the need for increased awareness of this disease in a broad medical and scientific community. Full article

Autoimmune gastritis (AIG) is characterized by the destruction of gastric parietal cells, resulting in hypochlorhydria and eventual achlorhydria, as oxyntic glands in the corpus are destroyed and become atrophic. The permanent loss of gastric acid has many impacts—both theoretical and documented. The most concerning of these are hypergastrinemia and increased N-nitroso compounds, both of which increase the risk of gastric cancers. While known deficiencies of B12 and iron are often replaced in AIG, acid is not. Moreover, patients with AIG are often prescribed acid suppression for a stomach that is decidedly no longer acidic, worsening the sequelae of gastric atrophy. Betaine hydrochloride (BHCL) is a short-acting acidifying agent, available over the counter in capsule form. Mealtime acid supplementation has an historic basis and could ameliorate many AIG-related gastrointestinal symptoms. Theoretically, acidification could also reduce the potential for hypergastrinemia and the production of N-nitroso compounds, consequently reducing the risk of gastric cancers. Supplemental vitamin C may also help in preventing gastric N-nitroso formation, regardless of the gastric pH. This narrative review describes the functions of gastric acid in gastrointestinal and immune health, documents the effects of hypochlorhydria in AIG, and proposes potential options for safely re-establishing the acid milieu of the stomach for patients with AIG. Full article

Gender differences and microbiota are gaining increasing attention. This study aimed to assess gender differences in gastric bacterial microbiota between subjects with healthy stomachs and those with autoimmune atrophic gastritis. This was a post hoc analysis of 52 subjects undergoing gastroscopy for dyspepsia (57.7% healthy stomach, 42.3% autoimmune atrophic gastritis). Gastric biopsies were obtained for histopathology and genomic DNA extraction. Gastric microbiota were assessed by sequencing the hypervariable regions of the 16SrRNA gene. The bacterial profile at the phylum level was reported as being in relative abundance expressed as 16SrRNA OTUs (>0.5%) and biodiversity calculated as Shannon-diversity index-H. All data were stratified for the female and male gender. Results showed that women with healthy stomachs had a higher gastric bacterial abundance and less microbial diversity compared to men. Likely due to hypochlorhydria and the non-acid intragastric environment, autoimmune atrophic gastritis seems to reset gender differences in gastric bacterial abundance and reduce biodiversity in males, showing a greater extent of dysbiosis in terms of reduced biodiversity in men. Differences between gender on taxa frequency at the phylum and genus level in healthy subjects and autoimmune atrophic gastritis were observed. The impact of these findings on the gender-specific natural history of autoimmune atrophic gastritis remains to be elucidated; in any case, gender differences should deserve attention in gastric microbiota studies. Full article

Intrinsically, enteric capsule shells offer several advantages compared to coating of dosage forms with enteric polymers. We undertook a systematic investigation to elucidate capsule-fill parameters that may result in premature gastric drug release from Vcaps^® Enteric capsules (Lonza CHI, Morristown, NJ, USA). Four model drugs with different ionization and solubility profiles were investigated: acetaminophen, ketoprofen, trimethoprim and atenolol. Different fill loads, diluents and drug-to-diluent ratios were explored. Enteric capsules were filled with drug or drug and diluent powder mix and underwent USP II dissolution testing using mini-vessels and paddles. Capsules were tested in pH 2 (0.01 M HCl) or pH 4.5 (3.2 × 10⁻⁵ M HCl) 200 mL acid media to simulate normal, fasted or hypochlorhydric gastric pH, respectively. Acetaminophen, trimethoprim and atenolol displayed premature gastric drug release from enteric capsules. The extent of premature release was dependent on drug solubility, ionization profile and capsule-fill level. At 100 mg drug-fill level, acetaminophen, trimethoprim and atenolol gave rise to 10.6, 12.2 and 83.1% drug release, respectively, in normal, fasted, gastric fluids. Diffusion layer pH of trimethoprim and atenolol in pH 2 media was determined to be pH 6.3 and 10.3, respectively. Upon increasing capsule-fill load using microcrystalline cellulose as a diluent, a significant reduction in premature gastric release was observed. However, including mannitol as a diluent was only effective at decreasing premature drug release at a low drug-to-diluent ratio. Systematic in vitro screening of enteric capsule fills needs to be conducted to ensure that drug product performance is not compromised. Full article

In recent years, it has been shown that gastrointestinal microflora has a substantial impact on the development of a large number of chronic diseases. The imbalance in the number or type of microbes in the gastrointestinal tract can lead to diseases and conditions, including autism spectrum disorder, celiac disease, Crohn’s disease, diabetes, and small bowel cancers. This can occur as a result of genetics, alcohol, tobacco, chemotherapeutics, cytostatics, as well as antibiotic overuse. Due to this, essential taxa can be lost, and the host’s metabolism can be severely affected. A less known condition called small intestine bacterial overgrowth (SIBO) can be seen in patients who suffer from hypochlorhydria and small intestine cancers. It is characterized as a state in which the bacterial population in the small intestine exceeds 10⁵–10⁶ organisms/mL. The latest examination methods such as double-balloon enteroscopy and wireless capsule endoscopy have the potential to increase the accuracy and precision of diagnosis and provide better patient care. This review paper aims to summarize the effect of the gastrointestinal environment on chronic disease severity and the development of cancers. Full article

Several nutraceutical products require gastric protection against the hostile environment in the stomach. Currently marketed synthetic and semi-synthetic coatings suffer from major shortcomings such as poor gastric protection, slow-release response to pH change, and the use of artificial ingredients. The challenge of coating natural products is further exacerbated by the relatively high gastric pH in the fed state. In this work, a novel natural enteric coating is presented as a breakthrough alternative to current solutions. Two coating systems were devised: (i) a triple-layer coating that comprises a wax layer embedded between two alginate-based coatings, and (ii) a double-layer coating, where an overcoat of organic acids (fumaric or citric acid) is applied to an alginate-based coating. The multi-layer architecture did not impact the pH-responsive nature of the coating even when more biologically relevant Krebs bicarbonate buffer of lower buffer capacity was used. Interestingly, the gastric protection barrier of organic acid-based coating remained resistant at elevated gastric pH 2, 3, or 4 for 2 h. This is the first report of using an alginate-based coating to provide gastric protection against fed-state stomach conditions (pH 2–4). Being biodegradable, naturally occurring, and with no limit on daily intake, the reported novel coating provides a superior platform to current coating solutions for pharmaceutical and nutraceutical products. Full article

The study aims to design a novel combination of drug-free solid self-nanoemulsifying drug delivery systems (S-SNEDDS) + solid dispersion (SD) to enhance cinnarizine (CN) dissolution at high pH environment caused by hypochlorhydria/achlorhydria. Drug-loaded and drug-free liquid SNEDDS were solidified using Neusilin^® US2 at 1:1 and 1:2 ratios. Various CN-SDs were prepared using freeze drying and microwave technologies. The developed SDs were characterized by differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD). In-vitro dissolution studies were conducted to evaluate CN formulations at pH 6.8. Drug-free S-SNEDDSs showed acceptable self-emulsification and powder flow properties. DSC and XRD showed that CN was successfully amorphized into SDs. The combination of drug-free S-SNEDDS + pure CN showed negligible drug dissolution due to poor CN migration into the formed nanoemulsion droplets. CN-SDs and drug-loaded S-SNEDDS showed only 4% and 23% dissolution efficiency (DE) while (drug-free S-SNEDDS + FD-SD) combination showed 880% and 160% enhancement of total drug release compared to uncombined SD and drug-loaded S-SNEDDS, respectively. (Drug-free S-SNEDDS + SD) combination offer a potential approach to overcome the negative impact of hypochlorhydria/achlorhydria on drug absorption by enhancing dissolution at elevated pH environments. In addition, the systems minimize the adverse effect of adsorbent on drug release. Full article

Helicobacter pylori infection is a severe global health problem that is closely associated with acid-related diseases and gastric malignancies. Eradicating H. pylori is strongly recommended for lowering peptic ulcer recurrence and preventing gastric cancer. The current approved H. pylori eradication regimen combines a proton pump inhibitor (PPI) with two antibiotics. Unfortunately, this regimen failed to meet expectations mostly due to antibiotic resistance and insufficient gastric acid suppression. Vonoprazan, a novel potassium-competitive acid blocker, showed promising results as a PPI replacement. Vonoprazan inhibits gastric acid secretion by acting as a reversible competitive inhibitor against potassium ions and forming disulfide bonds with the cysteine molecule of H⁺/K⁺-ATPase. Vonoprazan has superior pharmacological characteristics over PPI, such as no requirement for acid activation, stability in acidic conditions, shorter optimum acid suppression period, and resistance to cytochrome P (CYP)2C19 polymorphism. Several comparative randomized controlled trials and meta-analyses revealed the superiority of vonoprazan in eradicating H. pylori, notably the resistant strains. The adverse effect caused by vonoprazan is long-term acid suppression that may induce elevated gastrin serum, hypochlorhydria, and malabsorption. All vonoprazan studies have only been conducted in Japan. Further studies outside Japan are necessary for universally conclusive results. Full article

Gastric juice is a unique combination of hydrochloric acid (HCl), lipase, and pepsin. Acidic gastric juice is found in all vertebrates, and its main function is to inactivate microorganisms. The phylogenetic preservation of this energy-consuming and, at times, hazardous function (acid-related diseases) reflects its biological importance. Proton pump inhibitors (PPIs) are one of the most widely used drugs in the world. Due to the reduced prevalence of Helicobacter pylori infection as well as the increased use of inhibitors of gastric acid secretion, the latter has become the most important cause of gastric hypoacidity. In the present manuscript, we review the microbiological consequences of removing gastric acidity. The resulting susceptibility to infections has not been studied extensively, and focus has mainly been restricted to bacterial and parasitic agents only. The strongest evidence concerning the relationship between hypochlorhydria and predisposition to infections relates to bacterial infections affecting the gastrointestinal tract. However, several other clinical settings with increased susceptibility to infections due to inhibited gastric acidity are discussed. We also discuss the impact of hypochlorhydria on the gut microbiome. Full article

The number of patients with gastroesophageal problems taking proton pump inhibitors (PPIs) is increasing. Several studies suggested a possible association between PPIs and fracture risk, especially hip fractures, but the relationship remains contentious. This review aimed to investigate the longitudinal studies published in the last five years on the relationship between PPIs and fracture risk. The mechanism underlying this relationship was also explored. Overall, PPIs were positively associated with elevated fracture risk in multiple studies (n = 14), although some studies reported no significant relationship (n = 4). Increased gastrin production and hypochlorhydria are the two main mechanisms that affect bone remodeling, mineral absorption, and muscle strength, contributing to increased fracture risk among PPI users. As a conclusion, there is a potential relationship between PPIs and fracture risks. Therefore, patients on long-term PPI treatment should pay attention to bone health status and consider prophylaxis to decrease fracture risk. Full article