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Santacroce L, Topi S, Bottalico L, Charitos IA, Jirillo E. Current Knowledge about Gastric Microbiota with Special Emphasis on Helicobacter pylori-Related Gastric Conditions. Curr Issues Mol Biol 2024; 46:4991-5009. [PMID: 38785567 PMCID: PMC11119845 DOI: 10.3390/cimb46050299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2024] [Revised: 05/06/2024] [Accepted: 05/14/2024] [Indexed: 05/25/2024] Open
Abstract
The gastric milieu, because of its very low acidic pH, is very harsh for bacterial growth. The discovery of Helicobacter pylori (H.p.) has opened a new avenue for studies on the gastric microbiota, thus indicating that the stomach is not a sterile environment. Nowadays, new technologies of bacterial identification have demonstrated the existence of other microorganisms in the gastric habitat, which play an important role in health and disease. This bacterium possesses an arsenal of compounds which enable its survival but, at the same time, damage the gastric mucosa. Toxins, such as cytotoxin-associated gene A, vacuolar cytotoxin A, lipopolysaccharides, and adhesins, determine an inflammatory status of the gastric mucosa which may become chronic, ultimately leading to a gastric carcinoma. In the initial stage, H.p. persistence alters the gastric microbiota with a condition of dysbiosis, predisposing to inflammation. Probiotics and prebiotics exhibit beneficial effects on H.p. infection, and, among them, anti-inflammatory, antioxidant, and antibacterial activities are the major ones. Moreover, the association of probiotics with prebiotics (synbiotics) to conventional anti-H.p. therapy contributes to a more efficacious eradication of the bacterium. Also, polyphenols, largely present in the vegetal kingdom, have been demonstrated to alleviate H.p.-dependent pathologies, even including the inhibition of tumorigenesis. The gastric microbiota composition in health and disease is described. Then, cellular and molecular mechanisms of H.p.-mediated damage are clarified. Finally, the use of probiotics, prebiotics, and polyphenols in experimental models and in patients infected with H.p. is discussed.
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Affiliation(s)
- Luigi Santacroce
- Section of Microbiology and Virology, Interdisciplinary Department of Medicine, School of Medicine, University of Bari ‘Aldo Moro’, 70124 Bari, Italy;
| | - Skender Topi
- Department of Clinical Disciplines, University ‘Alexander Xhuvani’ of Elbasan, 3001 Elbasan, Albania; (S.T.)
| | - Lucrezia Bottalico
- Department of Clinical Disciplines, University ‘Alexander Xhuvani’ of Elbasan, 3001 Elbasan, Albania; (S.T.)
| | - Ioannis Alexandros Charitos
- Istituti Clinici Scientifici Maugeri IRCCS, Pneumology and Respiratory Rehabilitation Unit, Institute of Bari, 70124 Bari, Italy;
| | - Emilio Jirillo
- Section of Microbiology and Virology, Interdisciplinary Department of Medicine, School of Medicine, University of Bari ‘Aldo Moro’, 70124 Bari, Italy;
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Pathways of Gastric Carcinogenesis, Helicobacter pylori Virulence and Interactions with Antioxidant Systems, Vitamin C and Phytochemicals. Int J Mol Sci 2020; 21:ijms21176451. [PMID: 32899442 PMCID: PMC7503565 DOI: 10.3390/ijms21176451] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Revised: 08/21/2020] [Accepted: 08/31/2020] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori is a class one carcinogen which causes chronic atrophic gastritis, gastric intestinal metaplasia, dysplasia and adenocarcinoma. The mechanisms by which H. pylori interacts with other risk and protective factors, particularly vitamin C in gastric carcinogenesis are complex. Gastric carcinogenesis includes metabolic, environmental, epigenetic, genomic, infective, inflammatory and oncogenic pathways. The molecular classification of gastric cancer subtypes has revolutionized the understanding of gastric carcinogenesis. This includes the tumour microenvironment, germline mutations, and the role of Helicobacter pylori bacteria, Epstein Barr virus and epigenetics in somatic mutations. There is evidence that ascorbic acid, phytochemicals and endogenous antioxidant systems can modify the risk of gastric cancer. Gastric juice ascorbate levels depend on dietary intake of ascorbic acid but can also be decreased by H. pylori infection, H. pylori CagA secretion, tobacco smoking, achlorhydria and chronic atrophic gastritis. Ascorbic acid may be protective against gastric cancer by its antioxidant effect in gastric cytoprotection, regenerating active vitamin E and glutathione, inhibiting endogenous N-nitrosation, reducing toxic effects of ingested nitrosodimethylamines and heterocyclic amines, and preventing H. pylori infection. The effectiveness of such cytoprotection is related to H. pylori strain virulence, particularly CagA expression. The role of vitamin C in epigenetic reprogramming in gastric cancer is still evolving. Other factors in conjunction with vitamin C also play a role in gastric carcinogenesis. Eradication of H. pylori may lead to recovery of vitamin C secretion by gastric epithelium and enable regression of premalignant gastric lesions, thereby interrupting the Correa cascade of gastric carcinogenesis.
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Lahner E, Persechino S, Annibale B. Micronutrients (Other than iron) and Helicobacter pylori infection: a systematic review. Helicobacter 2012; 17:1-15. [PMID: 22221610 DOI: 10.1111/j.1523-5378.2011.00892.x] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Many micronutrients depend on a healthy stomach for absorption. Helicobacter pylori chronic gastritis may alter gastric physiology affecting homeostasis of vitamins and minerals. OBJECTIVES Systematic review to assess whether H. pylori infection is associated with reduced micronutrient levels (other than iron) in the plasma or gastric juice and whether low micronutrient levels are modified by eradication treatment. METHOD Medline was searched for relevant publications from inception to June 2010. Studies describing micronutrient levels in H. pylori-infected and not-infected adults and/or the effect of eradication treatment on micronutrient levels were included. FINDINGS Fifty-two publications were selected: 46 investigated the association between H. pylori infection and reduced micronutrient levels and 14 the effect of eradication treatment on micronutrient levels. Sixty-four studies investigated vitamins (23 ascorbic acid, four ß-carotene, 21 cobalamin, 11 folate, and five α-tocopherol) and 10 addressed minerals (one calcium, one copper, one magnesium, one phosphorus, three selenium, and three zinc). Pooled standardized mean differences in micronutrient levels showed positive associations with H. pylori infection for ascorbic acid (gastric juice, -1.087) and cobalamin (-0.744), and a positive effect of eradication treatment, which increased ascorbic acid in the gastric juice (-1.408) and serum cobalamin (-1.910). No significant association between infection and low folate levels was observed. Meta-analyses for other micronutrients were not performed owing to insufficient data. CONCLUSIONS Meta-analyses indicate that H. pylori infection is associated with reduced levels of ascorbic acid and cobalamin, supported by the positive effect of eradication treatment. For other micronutrients, further studies are needed.
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Affiliation(s)
- Edith Lahner
- Digestive and Liver Disease Unit, University Sapienza, Sant'Andrea Hospital, Via Grottarossa 1035, 00189 Rome, Italy
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Staudte H, Güntsch A, Völpel A, Sigusch B. Vitamin C attenuates the cytotoxic effects of Porphyromonas gingivalis on human gingival fibroblasts. Arch Oral Biol 2010; 55:40-5. [DOI: 10.1016/j.archoralbio.2009.11.009] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2009] [Revised: 10/27/2009] [Accepted: 11/16/2009] [Indexed: 10/20/2022]
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Higdon J, Frei B. Vitamin C, Vitamin E, and b-Carotene in Cancer Chemoprevention. PHYTOPHARMACEUTICALS IN CANCER CHEMOPREVENTION 2004. [DOI: 10.1201/9780203506707.ch21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
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Yang J, Kato K, Noguchi K, Dairaku N, Koike T, Iijima K, Imatani A, Sekine H, Ohara S, Sasano H, Shimosegawa T. Tochu (Eucommia ulmoides) leaf extract prevents ammonia and vitamin C deficiency induced gastric mucosal injury. Life Sci 2003; 73:3245-56. [PMID: 14561529 DOI: 10.1016/j.lfs.2003.06.011] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
The ingestion of dietary antioxidants, including vitamin C (VC), is suggested to play an important role in the prevention of gastric cancer associated with Helicobacter pylori (HP) infection. Recently, water extracts of Tochu (Du-zhong, Eucommia ulmoidea OLIVER) leaves (WETL) have been reported to have potent antioxidant and antimutagenic effects. The present study investigated the effect(s) of VC and WETL on gastric mucosal injury induced by ammonia and a VC deficient diet. Guinea pigs fed the water containing ammonia and/or a VC-deficient diet were simultaneously treated with WETL or VC. Intramucosal levels of thiobarubiturate reactive substances (TBARS), an index of lipid peroxidation, increased significantly in animals fed ammoniated water and VC-deficient diets. This was accompanied by accelerated cell proliferation and increases in immunohistochemical staining indices for oxidative stress-induced DNA adducts and strand breaks (e.g., BrdU-uptake, 8-OhdG, ssDNA and the TUNEL reaction). The administration of either WETL or VC to the ammoniated water and VC-deficient diets ameliorated the increases in intramucosal TBARS levels and labeling indices of BrdU, 8-OHdG, ssDNA and TUNEL, i.e., the levels were similar to those measured in the normal-fed control animals. These data suggest that insufficient VC ingestion may be an important risk factor for gastric cancer development in patients with HP infections. Furthermore, our results suggest that WETL or some constituent may contribute to the prevention of oxidative gastric injury that precedes carcinogenesis.
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Affiliation(s)
- Jing Yang
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Seiryo-machi, Aoba, Sendai, 980-8574, Miyagi, Japan
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Oliveira CPMS, Kassab P, Lopasso FP, Souza HP, Janiszewski M, Laurindo FRM, Iriya K, Laudanna AA. Protective effect of ascorbic acid in experimental gastric cancer: reduction of oxidative stress. World J Gastroenterol 2003; 9:446-448. [PMID: 12632494 PMCID: PMC4621558 DOI: 10.3748/wjg.v9.i3.446] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2002] [Revised: 03/23/2002] [Accepted: 04/06/2002] [Indexed: 02/06/2023] Open
Abstract
AIM Oxidative stress participates in the cell carcinogenesis by inducing DNA mutations. Our aim was to assess whether ascorbic acid, an antioxidant, could have a role in preventing ROS (Reactive Oxygen Species) generation in experimental gastric carcinoma in a rat model. METHODS Experimental gastric cancer was induced in twelve Wistar male rats (weighting 250-350 g) by profound duodeno-gastric reflux throught split gastrojenunostomy. The rats were allocated to the following groups: Group I (n=6) was the control; Group II (n=6) which was mantained with daily intake of tape water with Vitamin C (30 mg/Kg). After 6 or 12 months, samples of gastric tumor or non tumor mucosa were taken from the anastomosis of both groups. Oxidative stress was measured by superoxide quantification through lucigenin-amplified chemiluminescence base and by staining with Nitrobluetetrazolium. The histopathologic confirmation of adenocarcinoma was made by eosin-hemathoxilin method. RESULTS The intestinal type of gastric adenocarcinoma was microscopically identified in all animals of group I whereas only 3 rats of group II showed an adenocarcinoma without macroscopic evidence of them. The cancers were located in the anastomosis in all cases. Basal luminescence from tumor gastric tissue generated 38.4+/-6.8 count per minute/mg/X10(6) (mean+/-SD) and 14.9+/-4.0 count per minute/mg/X10(6), respectively, in group I and II animals (P<0.05). The Nitrobluetetrazolium method showed intense staining in tumor tissues but not in non neoplasic mucosa. CONCLUSION Experimental gastric tumors seem to produce more reactive oxygen species than non neoplasic gastric tissue. The reduction of oxidative stress and gastric tumor incidence in rats were induced by the intake of ascorbic acid. Therefore, it may have a role in the prevention of gastric carcinoma.
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Affiliation(s)
- Claudia P M S Oliveira
- Department of Gastroenterology School of Medicine, University of Sao Paulo, Av Dr Eneas de Carvalho Aguiar no 255, Instituto Central 9th Floor, 9159, 05403000 Sao Paulo, Brazil.
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Abstract
Antioxidants are substances capable of inhibiting oxidation. In chronic diseases, inflammatory response cells produce oxygen free radicals. Oxygen free radicals cause DNA damage, and this may lead to gene modifications that might be carcinogenic. Chronic Helicobacter pylori infection causes the production of DNA-damaging free radicals. In recent years, various groups have studied the effects of antioxidants, especially on H. pylori-associated gastric cancer. In most of the studies, it has been shown that H. pylori infection does affect the level of antioxidants measured in the gastric juice, but there are also controversial results. Recent experimental studies, both in vivo and in vitro, have shown that vitamin C and astaxanthin, a carotenoid, are not only free radical scavengers but also show antimicrobial activity against H. pylori. It has been shown that astaxanthin changes the immune response to H. pylori by shifting the Th1 response towards a Th2 T-cell response. Very few experimental studies support the epidemiologic studies, and further studies are needed to describe the effect and the mechanism of antioxidants in the H. pylori immune response.
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Affiliation(s)
- Y Akyön
- Hacettepe University, School of Medicine, Department of Microbiology and Clinical Microbiology, Ankara, Turkey.
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Meuwissen SG, Craanen ME, Kuipers EJ. Gastric mucosal morphological consequences of acid suppression: a balanced view. Best Pract Res Clin Gastroenterol 2001; 15:497-510. [PMID: 11403542 DOI: 10.1053/bega.2001.0189] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
In the chapter, an analysis of the literature on the relationship between Helicobacter pylori, the use of proton pump inhibitors and the development of atrophic gastritis is presented, and the difficulties of classifying gastritis and the new possibilities of quantifying chronic inflammation by morphometric analysis are discussed. The issue surrounding the necessity of eradicating H. pylori in H. pylori-positive patients has still not been solved. Most studies have now accepted that proton pump inhibitors indeed accelerate the onset of atrophic gastritis in H. pylori-positive patients, but evidence against such an association was published in one recent (Scandinavian) study; conclusions from this study have, however, been challenged by several groups. Some data are available on the efficacy of H. pylori eradication with regard to the prevention of atrophy. The limited significance of the development of parietal cell protrusions and fundic gland cysts is better understood, but much less is known of the development and long-term consequence of H. pylori-induced autoimmune gastritis. Finally, recent studies in H. pylori-positive patients indicate that treatment with proton pump inhibitors may promote bacterial N-nitrosation formation. These data taken together suggest that the eradication of H. pylori may be based not only on morphological arguments, but also on bacterial alterations in the gastric milieu.
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Affiliation(s)
- S G Meuwissen
- Department of Gastroenterology, 'Vrije Universiteit' Medical Centre, Amsterdam, The Netherlands
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Tuo BG, Yan YH, Ge ZL, Ou GW, Zhao K. Ascorbic acid secretion in the human stomach and the effect of gastrin. World J Gastroenterol 2000; 6:704-708. [PMID: 11819678 PMCID: PMC4688847 DOI: 10.3748/wjg.v6.i5.704] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the changes of gastric mucosal ascorbic acid secretion in patients with nonulcer dyspepsia and the effect of gastrin on it, and to relate any observed changes to H. pylori infection and mucosal histology.
METHODS: Ascorbic acid secretions in patients were examined by collecting continuously gastric juice for one hour after having aspirated and discarded fasting gastric juice. Using the clearance rate (mL/min) of ascorbic acid from blood to gastric juice represented ascorbic acid secretion in the gastric mucosa. Ascorbic acid concentrations in plasma and juice were measured by ferric reduced method.
RESULTS: Gastric ascorbic acid secretions in H. pylori -positive patients (1.46 mL/min, range 0.27-3.78) did not significantly differ from those in H. pylori -negative patients (1.25 mL/min, 0.47-3.14) (P > 0.05). There were no significant differences in ascorbic acid secretions between patients with mild (1.56 mL/min, 0.50-3.30), moderate (1.34 mL/min, 0.27-2.93) and severe (1.36 mL/min, 0.47-3.78) inflammation (P > 0.05). There were no significant differences in ascorbic acid secretions between patients without activity (1.45 mL/min, 0.27-3.14) and with mild (1.32 mL/min, 0.61-2.93), moderate (1.49 mL/min, 0.50-3.78) and severe (1.43 mL/min, 0.51-3.26) activity of chronic gastritis either (P > 0.05). Ascorbic acid secretions in patients with severe atrophy (0.56 mL/min, 0.27-1.20) were markedly lower than those in patients with out atrophy (1.51 mL/min, 0.59-3.30) and with mild (1.43 mL/min, 0.53-3.78) and moderate (1.31 mL/min, 0.47-3.16) atrophy (P < 0.005). There was a significant negative correlation between ascorbic acid secretion and severity of atrophy (correlation coefficient = -0.43, P < 0.005). After administration of pentagastrin, ascorbic acid secretions were markedly elevated (from 1.39 mL/min, 0.36-2.96 to 3.53 mL/min, 0.84-5.91) (P < 0.001).
CONCLUSION: Ascorbic acid secretion in gastric mucosa is not affected by H. pylori infection. Gastric ascorbic acid secretion is markedly related to the severity of atrophy, whereas not related to the severity of inflammation and activity. Gastrin may stimulate gastric ascorbic acid secretion. A decreased ascorbic acid secretion may be an important factor in the link between atrophic gastritis and gastric carcinogenesis.
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