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Gut Oct 2015The stomach is traditionally regarded as a hollow muscular sac that initiates the second phase of digestion. Yet this simple view ignores the fact that it is the most... (Review)
Review
The stomach is traditionally regarded as a hollow muscular sac that initiates the second phase of digestion. Yet this simple view ignores the fact that it is the most sophisticated endocrine organ with unique physiology, biochemistry, immunology and microbiology. All ingested materials, including our nutrition, have to negotiate this organ first, and as such, the stomach is arguably the most important segment within the GI tract. The unique biological function of gastric acid secretion not only initiates the digestive process but also acts as a first line of defence against food-borne microbes. Normal gastric physiology and morphology may be disrupted by Helicobacter pylori infection, the most common chronic bacterial infection in the world and the aetiological agent for most peptic ulcers and gastric cancer. In this state-of-the-art review, the most relevant new aspects of the stomach in health and disease are addressed. Topics include gastric physiology and the role of gastric dysmotility in dyspepsia and gastroparesis; the stomach in appetite control and obesity; there is an update on the immunology of the stomach and the emerging field of the gastric microbiome. H. pylori-induced gastritis and its associated diseases including peptic ulcers and gastric cancer are addressed together with advances in diagnosis. The conclusions provide a future approach to gastric diseases underpinned by the concept that a healthy stomach is the gateway to a healthy and balanced host. This philosophy should reinforce any public health efforts designed to eradicate major gastric diseases, including stomach cancer.
Topics: Gastric Mucosa; Humans; Stomach; Stomach Diseases
PubMed: 26342014
DOI: 10.1136/gutjnl-2014-307595 -
Gastroenterology Feb 2022The mucosa of the body of the stomach (ie, the gastric corpus) uses 2 overlapping, depth-dependent mechanisms to respond to injury. Superficial injury heals via surface... (Review)
Review
The mucosa of the body of the stomach (ie, the gastric corpus) uses 2 overlapping, depth-dependent mechanisms to respond to injury. Superficial injury heals via surface cells with histopathologic changes like foveolar hyperplasia. Deeper, usually chronic, injury/inflammation, most frequently induced by the carcinogenic bacteria Helicobacter pylori, elicits glandular histopathologic alterations, initially manifesting as pyloric (also known as pseudopyloric) metaplasia. In this pyloric metaplasia, corpus glands become antrum (pylorus)-like with loss of acid-secreting parietal cells (atrophic gastritis), expansion of foveolar cells, and reprogramming of digestive enzyme-secreting chief cells into deep antral gland-like mucous cells. After acute parietal cell loss, chief cells can reprogram through an orderly stepwise progression (paligenosis) initiated by interleukin-13-secreting innate lymphoid cells (ILC2s). First, massive lysosomal activation helps mitigate reactive oxygen species and remove damaged organelles. Second, mucus and wound-healing proteins (eg, TFF2) and other transcriptional alterations are induced, at which point the reprogrammed chief cells are recognized as mucus-secreting spasmolytic polypeptide-expressing metaplasia cells. In chronic severe injury, glands with pyloric metaplasia can harbor both actively proliferating spasmolytic polypeptide-expressing metaplasia cells and eventually intestine-like cells. Gastric glands with such lineage confusion (mixed incomplete intestinal metaplasia and proliferative spasmolytic polypeptide-expressing metaplasia) may be at particular risk for progression to dysplasia and cancer. A pyloric-like pattern of metaplasia after injury also occurs in other gastrointestinal organs including esophagus, pancreas, and intestines, and the paligenosis program itself seems broadly conserved across tissues and species. Here we discuss aspects of metaplasia in stomach, incorporating data derived from animal models and work on human cells and tissues in correlation with diagnostic and clinical implications.
Topics: Animals; Cell Plasticity; Cellular Reprogramming; Gastric Mucosa; Helicobacter Infections; Humans; Hyperplasia; Metaplasia; Parietal Cells, Gastric; Regeneration; Stomach
PubMed: 34728185
DOI: 10.1053/j.gastro.2021.10.036 -
American Journal of Physiology. Cell... Dec 2020Spasmolytic polypeptide/trefoil factor 2 (TFF2)-expressing metaplasia (SPEM) is a mucous-secreting reparative lineage that emerges at the ulcer margin in response to... (Review)
Review
Spasmolytic polypeptide/trefoil factor 2 (TFF2)-expressing metaplasia (SPEM) is a mucous-secreting reparative lineage that emerges at the ulcer margin in response to gastric injury. Under conditions of chronic inflammation with parietal cell loss, SPEM has been found to emerge and evolve into neoplasia. Cluster-of-differentiation gene 44 (CD44) is known to coordinate normal and metaplastic epithelial cell proliferation. In particular, CD44 variant isoform 9 (CD44v9) associates with the cystine-glutamate transporter xCT, stabilizes the protein, and provides defense against reactive oxygen species (ROS). xCT stabilization by CD44v9 leads to defense against ROS by cystine uptake, glutathione (GSH) synthesis, and maintenance of the redox balance within the intracellular environment. Furthermore, p38 signaling is a known downstream ROS target, leading to diminished cell proliferation and migration, two vital processes of gastric epithelial repair. CD44v9 emerges during repair of the gastric epithelium after injury, where it is coexpressed with other markers of SPEM. The regulatory mechanisms for the emergence of CD44v9 and the role of CD44v9 during the process of gastric epithelial regeneration are largely unknown. Inflammation and M2 macrophage infiltration have recently been demonstrated to play key roles in the induction of SPEM after injury. The following review proposes new insights into the functional role of metaplasia in the process of gastric regeneration in response to ulceration. Our insights are extrapolated from documented studies reporting oxyntic atrophy and SPEM development and our current unpublished findings using the acetic acid-induced gastric injury model.
Topics: Acetic Acid; Animals; Gastric Mucosa; Humans; Metaplasia; Regeneration; Stomach
PubMed: 32755448
DOI: 10.1152/ajpcell.00415.2019 -
JCI Insight Feb 2023Helicobacter pylori colonization of the gastric niche can persist for years in asymptomatic individuals. To deeply characterize the host-microbiota environment in H....
Helicobacter pylori colonization of the gastric niche can persist for years in asymptomatic individuals. To deeply characterize the host-microbiota environment in H. pylori-infected (HPI) stomachs, we collected human gastric tissues and performed metagenomic sequencing, single-cell RNA-Seq (scRNA-Seq), flow cytometry, and fluorescent microscopy. HPI asymptomatic individuals had dramatic changes in the composition of gastric microbiome and immune cells compared with noninfected individuals. Metagenomic analysis uncovered pathway alterations related to metabolism and immune response. scRNA-Seq and flow cytometry data revealed that, in contrast to murine stomachs, ILC2s are virtually absent in the human gastric mucosa, whereas ILC3s are the dominant population. Specifically, proportion of NKp44+ ILC3s out of total ILCs were highly increased in the gastric mucosa of asymptomatic HPI individuals, and correlated with the abundance of selected microbial taxa. In addition, CD11c+ myeloid cells and activated CD4+ T cells and B cells were expanded in HPI individuals. B cells of HPI individuals acquired an activated phenotype and progressed into a highly proliferating germinal-center stage and plasmablast maturation, which correlated with the presence of tertiary lymphoid structures within the gastric lamina propria. Our study provides a comprehensive atlas of the gastric mucosa-associated microbiome and immune cell landscape when comparing asymptomatic HPI and uninfected individuals.
Topics: Humans; Animals; Mice; Helicobacter pylori; Immunity, Innate; Single-Cell Gene Expression Analysis; Stomach; Gastric Mucosa; Plasma Cells; Helicobacter Infections
PubMed: 36810249
DOI: 10.1172/jci.insight.161042 -
Development (Cambridge, England) Feb 2016The stomach, an organ derived from foregut endoderm, secretes acid and enzymes and plays a key role in digestion. During development, mesenchymal-epithelial interactions... (Review)
Review
The stomach, an organ derived from foregut endoderm, secretes acid and enzymes and plays a key role in digestion. During development, mesenchymal-epithelial interactions drive stomach specification, patterning, differentiation and growth through selected signaling pathways and transcription factors. After birth, the gastric epithelium is maintained by the activity of stem cells. Developmental signals are aberrantly activated and stem cell functions are disrupted in gastric cancer and other disorders. Therefore, a better understanding of stomach development and stem cells can inform approaches to treating these conditions. This Review highlights the molecular mechanisms of stomach development and discusses recent findings regarding stomach stem cells and organoid cultures, and their roles in investigating disease mechanisms.
Topics: Animals; Body Patterning; Endoderm; Humans; Signal Transduction; Stem Cells; Stomach; Stomach Diseases
PubMed: 26884394
DOI: 10.1242/dev.124891 -
American Journal of Primatology May 2021Within the gastrointestinal tract, the physiochemical microenvironments are highly diversified among the different stages of food digestion. Accordingly, gut microbiome...
Within the gastrointestinal tract, the physiochemical microenvironments are highly diversified among the different stages of food digestion. Accordingly, gut microbiome composition and function vary at different gut sites. In this study, we examine and compare the compositional and functional potential between the stomach and colonic microbiome of wild Japanese macaques (Macaca fuscata yakui) living in the evergreen forest of Yakushima Island. We find a significantly lower microbial diversity in the stomach than in the colon, possibly due to the stomach's acidic and aerobic environment, which is suboptimal for microbial survival. According to past studies, the microbial taxa enriched in the stomach are aero- and acid-tolerant. By functional prediction through PICRUSt2, we reveal that the stomach microbiome is more enriched in pathways relating to the metabolism of simple sugars. On the contrary, the colonic microbiota is more enriched with fiber-degrading microbes, such as those from Lachnospiracea, Ruminococcaceae, and Prevotella. Our study shows a clear difference in the microbiome between the stomach and colon of Japanese macaques in both composition and function. This study provides a preliminary look at the alpha diversity and taxonomic composition within the stomach microbiome of Japanese macaques, a hindgut-fermenting nonhuman primate.
Topics: Animals; Colon; Gastrointestinal Microbiome; Macaca; Macaca fuscata; Stomach
PubMed: 33566369
DOI: 10.1002/ajp.23242 -
Cellular and Molecular Gastroenterology... 2021
Topics: GATA4 Transcription Factor; Gene Expression Regulation; Humans; Morphogenesis; Organogenesis; Stomach
PubMed: 34310908
DOI: 10.1016/j.jcmgh.2021.06.025 -
Journal of Nuclear Medicine Technology Jun 2019
Review
Topics: Gastric Emptying; Humans; Radionuclide Imaging; Stomach
PubMed: 31167827
DOI: 10.2967/jnmt.117.227892 -
The Journal of Physiology Sep 2016Adult tissues maintain function and architecture through robust homeostatic mechanisms mediated by self-renewing cells capable of generating all resident cell types.... (Review)
Review
Adult tissues maintain function and architecture through robust homeostatic mechanisms mediated by self-renewing cells capable of generating all resident cell types. However, severe injury can challenge the regeneration potential of such a stem/progenitor compartment. Indeed, upon injury adult tissues can exhibit massive cellular plasticity in order to achieve proper tissue regeneration, circumventing an impaired stem/progenitor compartment. Several examples of such plasticity have been reported in both rapidly and slowly self-renewing organs and follow conserved mechanisms. Upon loss of the cellular compartment responsible for maintaining homeostasis, quiescent or slowly proliferating stem/progenitor cells can acquire high proliferation potential and turn into active stem cells, or, alternatively, mature cells can de-differentiate into stem-like cells or re-enter the cell cycle to compensate for the tissue loss. This extensive cellular plasticity acts as a key mechanism to respond to multiple stimuli in a context-dependent manner, enabling tissue regeneration in a robust fashion. In this review cellular plasticity in the adult liver and stomach will be examined, highlighting the diverse cell populations capable of repairing the damaged tissue.
Topics: Animals; Cell Plasticity; Homeostasis; Humans; Liver; Regeneration; Stem Cells; Stomach
PubMed: 27028579
DOI: 10.1113/JP271769 -
World Journal of Gastroenterology Nov 2019The bacterium () infects the stomachs of approximately 50% of all humans. With its universal occurrence, high infectivity and virulence properties it is considered as... (Review)
Review
The bacterium () infects the stomachs of approximately 50% of all humans. With its universal occurrence, high infectivity and virulence properties it is considered as one of the most severe global burdens of modern humankind. It has accompanied humans for many thousands of years, and due to its high genetic variability and vertical transmission, its population genetics reflects the history of human migrations. However, especially complex demographic events such as the colonisation of Europe cannot be resolved with population genetic analysis of modern strains alone. This is best exemplified with the reconstruction of the 5300-year-old genome of the Iceman, a European Copper Age mummy. Our analysis provided precious insights into the ancestry and evolution of the pathogen and underlined the high complexity of ancient European population history. In this review we will provide an overview on the molecular analysis of in mummified human remains that were done so far and we will outline methodological advancements in the field of ancient DNA research that support the reconstruction and authentication of ancient genome sequences.
Topics: Body Remains; DNA, Ancient; DNA, Bacterial; Genome, Bacterial; Helicobacter Infections; Helicobacter pylori; Humans; Mummies; Stomach; Virulence
PubMed: 31754290
DOI: 10.3748/wjg.v25.i42.6289