Gastric Dysbiosis Research Articles

Medications to Modify Aspiration Risk: Those That Add to Risk and Those That May Reduce Risk.

Aspiration pneumonia results from the abnormal entry of fluids into the respiratory tract. We present a review of drugs known to affect the risk of aspiration. Drugs that increase the risk of aspiration pneumonia can be broadly divided into those that affect protective reflexes (like cough and swallowing) due to direct or indirect mechanisms, and drugs that facilitate gastric dysbiosis or affect esophageal and intestinal motility. Chief among the first group are benzodiazepines and antipsychotics, while proton pump inhibitors are the most well-studied in the latter group. Pill esophagitis may also exacerbate swallowing dysfunction. On the other hand, some research has also focused on pharmaceutical modulation of the risk of aspiration pneumonia. Angiotensin-converting enzyme inhibitors have been demonstrated to be associated with a decrease in the hazard of aspiration pneumonia in high-risk patients of Chinese or Japanese origin. Drugs like amantadine, nicergoline, or folic acid have shown some promising results in stroke patients, although the available evidence is thus far not enough to allow for any meaningful conclusions. Importantly, antimicrobial prophylaxis has been proven to be ineffective. Focusing on modifiable risk factors for aspiration pneumonia is relevant since this may help to reduce the incidence of this often severe problem. Among these, several commonly used drug classes have been shown to increase the risk of aspiration pneumonia. These drugs should be withheld in the high-risk population whenever possible, alongside general measures, such as the semirecumbent position during sleep and feeding.

The Most Recent Insights into the Roots of Gastric Cancer.

Helicobacter pylori (H. pylori) is the most common bacterial infection worldwide, usually being acquired during childhood, and its persistence into adulthood represents one of the main contributors of gastric carcinogenesis. Based on these statements, it would be of great importance to know if the most early premalignant transformation occurs in children or later since, this would enable the development of effective anti-tumorigenesis strategies. The interplay between H. pylori virulence factors, the host's responses modified by this infection, and the gastric microecology are complex and eventually lead to the development of gastric cancer in susceptible individuals. Several biomarkers were identified as major contributors of this long-lasting process, such as pepsinogens, gastrin 17, lipid-, glucose- and iron-metabolism parameters, immunity players, aberrant bacterial DNA methylation, H. pylori virulence factors, and hallmarks of gastric dysbiosis. Several of these biomarkers were also identified in children with H. pylori infection, independently of the presence of premalignant lesions, which were also proven to be present in a subgroup of H. pylori-infected children, especially those carrying extremely virulent strains. Therefore, the most incipient premalignant gastric changes might indeed occur early during childhood, opening a promising research gate for further studies to delineate the border between infection and cancer.

Linking dysbiosis to precancerous stomach through inflammation: Deeper than and beyond imaging.

Upper gastrointestinal endoscopy is considered the gold standard for gastric lesions detection and surveillance, but it is still associated with a non-negligible rate of missing conditions. In the Era of Personalized Medicine, biomarkers could be the key to overcome missed lesions or to better predict recurrence, pushing the frontier of endoscopy to functional endoscopy. In the last decade, microbiota in gastric cancer has been extensively explored, with gastric carcinogenesis being associated with progressive dysbiosis. Helicobacter pylori infection has been considered the main causative agent of gastritis due to its interference in disrupting the acidic environment of the stomach through inflammatory mediators. Thus, does inflammation bridge the gap between gastric dysbiosis and the gastric carcinogenesis cascade and could the microbiota-inflammation axis-derived biomarkers be the answer to the unmet challenge of functional upper endoscopy? To address this question, in this review, the available evidence on the role of gastric dysbiosis and chronic inflammation in precancerous conditions of the stomach is summarized, particularly targeting the nuclear factor-κB (NF-κB), toll-like receptors (TLRs) and cyclooxygenase-2 (COX-2) pathways. Additionally, the potential of liquid biopsies as a non-invasive source and the clinical utility of studied biomarkers is also explored. Overall, and although most studies offer a mechanistic perspective linking a strong proinflammatory Th1 cell response associated with, but not limited to, chronic infection with Helicobacter pylori, promising data recently published highlights not only the diagnostic value of microbial biomarkers but also the potential of gastric juice as a liquid biopsy pushing forward the concept of functional endoscopy and personalized care in gastric cancer early diagnosis and surveillance.

Morphine use induces gastric microbial dysbiosis driving gastric inflammation through TLR2 signalling which is attenuated by proton pump inhibition.

Opioids are the standard drug for pain management; however, their effects on gastric dysfunction are relatively understudied. Opioid users have a higher incidence of gastric pathology leading to increased hospitalization. Herein, we investigated the consequences of morphine use on gastric pathology and the underlying mechanisms. We further investigated the therapeutic benefit of proton pump inhibition to overcome morphine-mediated gastric inflammation. Mice were implanted with 25 mg slow-release morphine and placebo pellets. Gastric microbiome analyses were performed. Gastric damage was assayed. Gastric pH was measured. Germ-free and TLR2KO mice were used to investigate the mechanisms. Gastroprotective studies were performed with the proton pump inhibitor (PPI) omeprazole. Chronic morphine treatment alters gastric microbial composition and induces preferential expansion of pathogenic bacterial communities such as Streptococcus and Pseudomonas. Morphine causes disruption of the gastric mucosal layer, increases apoptosis, and elevates inflammatory cytokines. Moreover, morphine-mediated gastric pathology was significantly attenuated in germ-free mice, and reconstitution of morphine gastric microbiome in germ-free mice resulted gastric inflammation. In addition, morphine-mediated gastric inflammation was attenuated in TLR2KO mice. Morphine causes a decrease in gastric pH, which contributes to gastric dysbiosis leads to gastric inflammation. Omeprazole treatment inhibits gastric acidity, rescuing morphine-induced gastric dysbiosis and preventing inflammation. This study attributes morphine-induced gastric acidity as a driver of gastric dysbiosis and pathology and proposes the therapeutic use of PPI as an inexpensive approach for the clinical management of morphine-associated pathophysiology.

Diagnostic approach to Helicobacter pylori-related gastric oncogenesis.

Helicobacter pylori (H. pylori) is a causative agent of peptic ulcer disease and plays an important role in the development of various other upper and lower gastrointestinal tract and systemic diseases; in addition to carcinogenesis and the development of mucosa-associated lymphoid tissue lymphoma, extragastric manifestations of H. pylori are increasingly being unraveled. Therefore, prompt and accurate diagnosis is essential. Within this narrative review we present an overview of the current trend in the diagnosis of H. pylori infection and its potential oncogenic sequelae, including gastric mucosa atrophy, intestinal metaplasia, dysplasia and gastric cancer. Signs of H. pylori-related gastric cancer risk can be assessed by endoscopy using the Kyoto classification score. New technology, such as optical or digital chromoendoscopy, improves diagnostic accuracy and provides information regarding H. pylori-related gastric preneoplastic and malignant lesions. In addition, a rapid urease test or histological examination should be performed, as these offer a high diagnostic sensitivity; both are also useful for the diagnosis of sequelae including gastric and colon neoplasms. Culture is necessary for resistance testing and detecting H. pylori-related gastric dysbiosis involved in gastric oncogenesis. Likewise, molecular methods can be utilized for resistance testing and detecting H. pylori-related gastric cancer development and progression. Noninvasive tests, such as the urea breath and stool antigen tests, can also be implemented; these are also suitable for monitoring eradication success and possibly for detecting H. pylori-related gastric malignancy. Serological tests may help to exclude infection in specific populations and detect gastric and colon cancers. Finally, there are emerging potential diagnostic biomarkers for H. pylori-related gastric cancer.

Role of Helicobacter pylori and Other Environmental Factors in the Development of Gastric Dysbiosis.

Microbiomes are defined as complex microbial communities, which are mainly composed of bacteria, fungi, and viruses residing in diverse regions of the human body. The human stomach consists of a unique and heterogeneous habitat of microbial communities owing to its anatomical and functional characteristics, that allow the optimal growth of characteristic bacteria in this environment. Gastric dysbiosis, which is defined as compositional and functional alterations of the gastric microbiota, can be induced by multiple environmental factors, such as age, diet, multiple antibiotic therapies, proton pump inhibitor abuse, H. pylori status, among others. Although H. pylori colonization has been reported across the world, chronic H. pylori infection may lead to serious consequences; therefore, the infection must be treated. Multiple antibiotic therapy improvements are not always successful because of the lack of adherence to the prescribed antibiotic treatment. However, the abuse of eradication treatments can generate gastric dysbiotic states. Dysbiosis of the gastric microenvironment induces microbial resilience, due to the loss of relevant commensal bacteria and simultaneous colonization by other pathobiont bacteria, which can generate metabolic and physiological changes or even initiate and develop other gastric disorders by non-H. pylori bacteria. This systematic review opens a discussion on the effects of multiple environmental factors on gastric microbial communities.

The impact of Helicobacter pylori infection, eradication therapy, and probiotics intervention on gastric microbiota in young adults.

The impact of probiotics on non-Helicobacter pylori gastric microbiota and its role in microbial restoration after eradication were relatively unknown. We aimed to explore the effect of H.pylori eradication and probiotic intervention on gastric microbiota in young adults. Fifty-six H.pylori-negative and 95 H.pylori-positive subjects aged 19-30 were included in this study. H.pylori-infected individuals were randomly assigned to quadruple therapy, probiotics supplemented quadruple therapy, or probiotics monotherapy group. Gastric mucosa and gastric juice samples were collected before and 2months after treatment for 16SrRNA gene sequencing. The gastric microbial community structure and composition differed from H.pylori-negative subjects 2months after successful H.pylori eradication. The α diversity of gastric mucosal microbiota significantly increased and was higher than H.pylori-negative subjects, while the α diversity of gastric juice microbiota decreased and was lower than the H.pylori-negative. After probiotics supplemented eradication treatment, Bifidobacterium was enriched in gastric mucosa, Lactobacillus was enriched in gastric juice, potentially pathogenic bacteria such as Fusobacterium and Campylobacter decreased, and the microbial diversity was closer to that of H.pylori-negative subjects compared to quadruple therapy group. Probiotics monotherapy significantly altered the diversity, community structure, and composition of gastric microbiota but showed no advantage in H.pylori inhibition and upregulating beneficial bacteria such as Bifidobacterium and Lactobacillus and related metabolism pathways. Certain potentially pathogenic bacteria such as Fusobacterium increased after probiotic monotherapy. H.pylori eradication significantly disrupted gastric microbiota in young adults and could not be restored in a short time. Probiotics supplementation partially helped restore the gastric dysbiosis caused by eradication therapy, but it might be unnecessary for H.pylori-infected young adults to take probiotics alone.

Human stomach microbiota: Effects on health and disease

The gut microbiota is a complex ecological community, consisting of trillions of microbes which include bacteria, viruses, fungi and protozoa. The stomach was previously considered as a sterile site uninhabited by microbes due to its hostile environmental conditions. Breaking this concept, Helicobacter pylori was the first pathogen reported to inhabit the stomach. Recent studies have suggested that the stomach harbours transient as well as certain commensal bacterial and fungal species. The five major microbial phyla in the stomach have been identified as Firmicutes, Bacteroidetes, Actinobacteria, Fusobacteria and Proteobacteria. The composition of gastric microbiota is dynamic and is affected by several factors. These include age group, dietary habits, medication use, inflammation of gastric mucosa and H. pylori colonization. Further, the role of host genetics has recently been studied in maintaining the stomach microbiota. Mutations in host genes may affect the host’s immune response towards commensal bacteria and reduce their number and diversity. The essential multiple roles of gut microorganisms include maintaining homeostasis in the gut, contributing to immune function and extraction of nutrients and energy from our diets. Loss of the normal balance between the gut microbiota and host has been associated with several abnormal conditions and disorders such as obesity, malnutrition, inflammatory bowel diseases (IBD), neurological disorders, and cancer. In the stomach, the interaction between H. pylori and the gastric microbiota can also influence gastric dis­ease progression. Further studies should focus on addressing the role of gastric dysbiosis in health and disease. Identifying gastric microbiota is essential to understand how the gut microbiota and H. pylori affect health and disease.

Gastric microbiome profile throughout gastric carcinogenesis: beyond helicobacter

Background Gastric dysbiosis has been hinted as a potential cause of gastric cancer. However, changes in microbiome throughout the major stages of gastric carcinogenesis remain mostly unknown. Objective To describe gastric microbiome at different stages, analysing for the first time dysbiosis specifically in patients with early gastric cancer (EGC). Methods Cross-sectional study including patients (n = 77) with endoscopically and histologically confirmed normal stomachs (controls; n = 25), advanced atrophic gastritis with intestinal metaplasia (IM; n = 18) and EGC (n = 34). Endoscopic biopsies from antrum and corpus (n = 154) were analyzed. Next-generation sequencing was performed characterizing microbial communities down to the species level based on full-length 16SrRNA gene profiling. Results Significant differences were found in the microbiome profile between the groups. Firmicutes were more frequent (p = .012) and Proteobacteria were less frequent (p = .04) both in the IM and EGC when comparing to controls. Relative frequency of Helicobacter pylori, when present, was much higher in the controls (83%) when comparing to the other groups (IM 1%, EGC 27%; p = .006), being the dominant bacteria only in the controls. Dysbiosis was present already and more significantly at the IM stage, with two bacteria progressively increasing from controls to IM then to cancer: Gemella from 1.48 to 3.9% (p = .014); and Streptococcus from 19.3 to 33.7% (p = .04), being the EGC dominant bacteria. Conclusions Our results confirm Helicobacter pylori dominancy in non-atrophic stomachs and progressive dysbiosis throughout gastric carcinogenesis. Gemella but particularly Streptococcus is significantly increased in patients with EGC. Specific modulation of these bacteria may change gastric cancer risk.

Pullulation bactérienne gastrique : une observation histologique inhabituelle, à ne pas méconnaître

Gastric bacterial overgrowth is a rare situation, which may be associated with short- and long-term complications. It must be known from pathologists, since it might be detected incidentally at histological examination of gastric biopsies. We report here the case of a 74-year old woman, obese, without significant medical history, apart from a gastro-esophageal reflux treated by the long-term administration of proton pump inhibitors (PPI). In this patient, gastric bacterial overgrowth was detected at histological examination of gastric biopsies performed after colectomy for left colon adenocarcinoma. Large clusters of small, round, "coccoid" bacteria were present in the gastric mucus. Their characteristics were suggestive of enterobacteria. Bacterial proliferation was associated with severe and diffuse lesions of active gastritis. The course was rapidly unfavorable, and the patient rapidly deceased with multiple infections and multi-organ failure. In our observation, the pathogenesis of gastric bacterial overgrowth was probably multifactorial. It might have been facilitated by long-term PPI treatment and obesity, which are known risk factors, and promoted, in the post-operative setting, by multiple infections and immune failure. Our observation underlines that gastric bacterial overgrowth might be associated with severe gastritis, which might justify antibiotherapy. Other consequences of prolonged gastric dysbiosis cannot be excluded, such as the promotion of neoplastic lesions.

Long-term persistence of gastric dysbiosis after eradication of Helicobacter pylori in patients who underwent endoscopic submucosal dissection for early gastric cancer

BackgroundGastric microbiome, other than Helicobacter pylori, plays a role in the tumorigenesis of gastric cancer (GC). Patients who undergo endoscopic submucosal dissection for early GC have a high risk of developing metachronous GC even after successful eradication of H. pylori. Thus, we investigated the microbial profiles and associated changes in such patients after the eradication of H. pylori.MethodsA total of 19 H. pylori-infected patients with early GC who were or to be treated by endoscopic resection, with paired biopsy samples at pre- and post-eradication therapy, were retrospectively enrolled. Ten H. pylori-negative patients were enrolled as controls. Biopsy samples were analyzed using 16S rRNA sequencing.ResultsH. pylori-positive patients exhibited low richness and evenness of bacteria with the deletion of several genera, including Blautia, Ralstonia, Faecalibacterium, Methylobacterium, and Megamonas. H. pylori eradication partially restored microbial diversity, as assessed during a median follow-up at 13 months after eradication therapy. However, post-eradication patients had less diversity than that in the controls and possessed a lower abundance of the five genera mentioned above. The eradication of H. pylori also altered the bacterial composition, but not to the same extent as that in controls. The microbial communities could be clustered into three separate groups: H. pylori-negative, pre-eradication, and post-eradication.ConclusionChanges in dysbiosis may persist long after the eradication of H. pylori in patients with a history of GC. Dysbiosis may be involved in the development of both primary and metachronous GC after the eradication of H. pylori in such patients.

Certain Indicators of Diclofenac Sodium Pharmacokinetics in Patients with Rheumatoid Arthritis Considering Comorbide States

Introduction: Much attention is paid to pharmacokinetic (FK) researches for studying the processes ofsupply, distribution, biotransformation and excretion of medications at the present time, as well as identifyinglinks between medical substances concentration and (or) its metabolites in biological fluids and tissues, andits pharmacological effect. In the treatment of rheumatoid arthritis (RA), non-steroidal anti-inflammatorydrugs (NSAID) are widely used for a symptom therapy, where Diclofenac Sodium (DS) is most commonlyprescribed. Duration of anti-inflammatory effect, effectiveness of NSAID in whole are directly dependent onthe level of effective concentration of medications and circulation duration in blood in free form.The Aim of the present research work is to study in a comparative aspect certain indicators of DiclofenacSodium pharmacokinetics in patients with rheumatoid arthritis with gastric microbiocenosis disorders(gastric dysbiosis) and without disorders (without dysbiosis).Materials and Method: 38 patients at the age from 18 to 60 years were examined, with I-II-III degree ofdisease activity. In addition to the general clinical examination, an immune-enzyme method and urease testwere carried out to determine Helicobacter Pylori and highly effective liquid chromatography to determineDiclofenac pharmacokinetics.Results: Conducted researches and analysis of their results indicate that in conditions of rheumatoid arthritis,particularly, in the presence of comorbid states, there is a decrease in the metabolism rate and an extension ofNSAID half-excretion period, which increases the risk of side effects, especially to the gastrointestinal tract,and significantly affects the disease course and the results of the treatment.Conclusion: In conditions of rheumatoid arthritis with comorbid states, there is more frequent occurrenceof the NSAID side effects. Research conducted and analysis of their results indicate that in conditionsof rheumatoid arthritis, particularly at comorbid states, there are reasonable changes in the NSAIDpharmacokinetics. The decreasing of metabolic rate and the extension of the NSAID half-excretion increasesthe risk of side effects, especially on the side of the GIT, which significantly affects the disease course andresults of the treatment. This circumstance dictates the need to take these results into account in the treatmentof the studied pathology and in the development of a personalized approach to the treatment of rheumatoidarthritis

Risk factors associated with gastric malignancy during chronic Helicobacter pylori Infection.

Chronic Helicobacter pylori (Hp) infection is considered to be the single most important risk factor for the development of gastric adenocarcinoma in humans, which is a leading cause of cancer-related death worldwide. Nonetheless, Hp infection does not always progress to malignancy, and, gastric adenocarcinoma can occur in the absence of detectable Hp carriage, highlighting the complex and multifactorial nature of gastric cancer. Here we review known contributors to gastric malignancy, including Hp virulence factors, host genetic variation, and multiple environmental variables. In addition, we assess emerging evidence that resident gastric microflora in humans might impact disease progression in Hp-infected individuals. Molecular approaches for microbe identification have revealed differences in the gastric microbiota composition between cancer and non-cancerous patients, as well as infected and uninfected individuals. Although the reasons underlying differences in microbial community structures are not entirely understood, gastric atrophy and hypochlorhydria that accompany chronic Hp infection may be a critical driver of gastric dysbiosis that promote colonization of microbes that contribute to increased risk of malignancy. Defining the importance and role of the gastric microbiota as a potential risk factor for Hp-associated gastric cancer is a vital and exciting area of current research.

Modification of the Gastric Mucosal Microbiota by a Strain-Specific Helicobacter pylori Oncoprotein and Carcinogenic Histologic Phenotype.

Helicobacter pylori is the strongest risk factor for gastric adenocarcinoma; however, most infected individuals never develop this malignancy. Strain-specific microbial factors, such as the oncoprotein CagA, as well as environmental conditions, such as iron deficiency, augment cancer risk. Importantly, dysbiosis of the gastric microbiota is also associated with gastric cancer. To investigate the combinatorial effects of these determinants in an in vivo model of gastric cancer, Mongolian gerbils were infected with the carcinogenic cag+H. pylori strain 7.13 or a 7.13 cagA isogenic mutant, and microbial DNA extracted from gastric tissue was analyzed by 16S rRNA sequencing. Infection with H. pylori significantly increased gastric inflammation and injury, decreased α-diversity, and altered microbial community structure in a cagA-dependent manner. The effect of iron deficiency on gastric microbial communities was also investigated within the context of infection. H. pylori-induced injury was augmented under conditions of iron deficiency, but despite differences in gastric pathology, there were no significant differences in α- or β-diversity, phyla, or operational taxonomic unit (OTU) abundance among infected gerbils maintained on iron-replete or iron-depleted diets. However, when microbial composition was stratified based solely on the severity of histologic injury, significant differences in α- and β-diversity were present among gerbils harboring premalignant or malignant lesions compared to gerbils with gastritis alone. This study demonstrates that H. pylori decreases gastric microbial diversity and community structure in a cagA-dependent manner and that as carcinogenesis progresses, there are corresponding alterations in community structure that parallel the severity of disease.IMPORTANCE Microbial communities are essential for the maintenance of human health, and when these communities are altered, hosts can become susceptible to inflammation and disease. Dysbiosis contributes to gastrointestinal cancers, and specific bacterial species are associated with this phenotype. This study uses a robust and reproducible animal model to demonstrate that H. pylori infection induces gastric dysbiosis in a cagA-dependent manner and further that dysbiosis and altered microbial community structure parallel the severity of H. pylori-induced gastric injury. Ultimately, such models of H. pylori infection and cancer that can effectively evaluate multiple determinants simultaneously may yield effective strategies for manipulating the gastric microbiota to prevent the development of gastric cancer.

1133 – ΑΑInduction of Gastric Dysbiosis by Carcinogenic Helicobacter Pylori is Altered by the Oncoprotein Caga and Segregates with Premalignant and Malignant Histologic Phenotypes

1133 – ΑΑInduction of Gastric Dysbiosis by Carcinogenic Helicobacter Pylori is Altered by the Oncoprotein Caga and Segregates with Premalignant and Malignant Histologic Phenotypes

Helicobacter pylori Infection and Gastric Dysbiosis: Can Probiotics Administration Be Useful to Treat This Condition?

Helicobacter pylori (Hp) is responsible for one of the most common infections in the world. The prevalence exceeds 50% of the population in developing countries, and approximately one-third of the adults are colonized in North Europe and North America. It is considered a major pathogenic agent of chronic gastritis, peptic ulcer, atrophic gastritis, gastric cancer, and mucosa-associated lymphoid tissue lymphoma (MALT). Hp colonization modifies the composition of gastric microbiota that could drive the development of gastric disorders. Currently, an emerging problem in Hp treatment is represented by the increasing rate of antimicrobial therapy resistance. In this context, the search for adjuvant agents can be very useful to overcome this issue and probiotics administration can represent a valid option. The aim of this review is to describe the gastric microbiota changes during Hp colonization, the mechanisms of action, and a possible role of probiotics in the treatment of this infection.

Gastrointestinal Cancer

Gastrointestinal Cancer

Colonization of an acid resistant Kingella denitrificans in the stomach may contribute to gastric dysbiosis by Helicobacter pylori

In the stomach of a gastric ulcer patient who had been administered an anti-acid, a gram-negative and urease-negative bacillus similar in size to Helicobacter pylori was infected together with H. pylori. According to biochemical test and 16S rRNA gene analysis, the urease-negative bacterium was identified as Kingella denitrificans, a human nasopharyngeal commensal. In contrast to the standard strain of K. denitrificans, the isolate showed catalase activity, did not produce acid from glucose, and exhibited acid tolerance. Acid tolerance of H. pylori was increased by cocultivation with the K. denitrificans isolate, but not with other isolates of K. denitrificans. Disruption of physiological and immunological niche by dysbiotic colonization of bacterium may provide pathological attributes to human stomach. Collectively, a careful administration of anti-acids to the elderly, especially those with atrophic gastritis, is necessary to avoid repression of the gastric barrier to bacteria.