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Ethier R, Krishnamurthy A, Jeffrey M, Tompkins TA. Profiling of Metabolites in a Fermented Soy Dietary Supplement Reinforces its Role in the Management of Intestinal Inflammation. Mol Nutr Food Res 2024; 68:e2300770. [PMID: 38522032 DOI: 10.1002/mnfr.202300770] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 02/19/2024] [Indexed: 03/25/2024]
Abstract
SCOPE Gastro-AD (GAD) is a soy flour derived product that undergoes an industrial fermentation with Lactobacillus delbrueckii R0187 and has demonstrated clinical effects in gastroesophageal reflux and peptic ulcer symptom resolution. The aim of this study is to describe and link GAD's metabolomic profile to plausible mechanisms that manifest and explain the documented clinical outcomes. METHODS AND RESULTS 1H NMR spectroscopy with multivariate statistical analysis is used to characterize the prefermented soy flour and GAD products. The acquired spectra are screened using various resources and the molecular assignments are confirmed using total correlation spectroscopy (TOCSY). Peaks corresponding to different metabolites are integrated and compared between the two products for relative changes. HPLC and GC are used to quantify some specific molecules. NMR analyses demonstrate significant changes in the composition of various assigned bioactive moieties. HPLC and GC analysis demonstrate deglycation of isoflavones after fermentation, resulting in estrogenically active secondary metabolites that have been previously shown to help to reduce inflammation. CONCLUSION The identification of bioactive molecules, such as genistein and SCFAs, capable of modulating anti-inflammatory signaling cascades in the stomach's gastric and neuroendocrine tissues can explain the reported biological effects in GAD and is supported by in vivo data.
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Affiliation(s)
- Richard Ethier
- Richard Ethier Consulting, Montreal, Quebec, H4C 2J9, Canada
| | - Arun Krishnamurthy
- Purity-IQ Inc., Suite# 102, 150 Research Lane, Guelph, Ontario, N1G 4T2, Canada
| | - Michael Jeffrey
- Faculty of Science, Engineering & Information Technology, Durham College, Oshawa, Ontario, L1G 0C5, Canada
| | - Thomas A Tompkins
- Lallemand Bio-Ingredients, 1620 rue Prefontaine, Montreal, Quebec, H1W 2N8, Canada
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Tovey FI. Role of dietary phospholipids and phytosterols in protection against peptic ulceration as shown by experiments on rats. World J Gastroenterol 2015; 21:1377-1384. [PMID: 25663757 PMCID: PMC4316080 DOI: 10.3748/wjg.v21.i5.1377] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2014] [Accepted: 12/22/2014] [Indexed: 02/06/2023] Open
Abstract
Geographically the prevalence of duodenal ulceration is related to the staple foods in the diet in regions of developing countries where the diet is stable. It is higher in regions where the diet is based on milled rice, refined wheat or maize, yams, cassava, sweet potato, or green bananas, and is lower in regions where the staple diet is based on unrefined wheat or maize, soya, certain millets or certain pulses. Experiments on rat gastric and duodenal ulcer models showed that it was the lipid fraction in staple foods from low prevalence areas that was protective against both gastric and duodenal ulceration, including ulceration due to non-steroidal anti-inflammatory drugs (NSAIDs). It also promoted ulcer healing. The lipid from the pulse, Dolichos biflorus, horse gram which was highly protective was used to identify the fractions with protective activity in the lipid. The protective activity lay in the phospholipid, sterol and sterol ester fractions. In the phospholipid fraction phosphatidyl choline (lethicin) and phosphatidyl ethanolamine (cephalin) were predominant. In the sterol fraction the sub-fractions showing protective activity contained β-sitosterol, stigmasterol, and an unidentified isomer of β-sitosterol. The evidence from animal models shows that certain dietary phospholipids and phytosterols have a protective action against gastroduodenal ulceration, both singly and in combination. This supports the protective role of staple diets in areas of low duodenal ulcer prevalence and may prove to be of importance in the prevention and treatment of duodenal ulceration and management of recurrent ulcers. A combination of phospholipids and phytosterols could also play an important role in protection against ulceration due to NSAIDs.
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Abstract
The prevalence of duodenal ulceration in India, Africa, China and other developing countries is high in some regions and low in others, despite a high prevalence of Helicobacter pylori infection throughout the areas. This variation is related to the staple diet of the regions involved. In regions where, because of the climate, the staple food is milled white rice, wheat or maize, or cassava, yams,sweet potato and green bananas the prevalence of duodenal ulcer is higher than in regions where the staple diet is based on unrefined wheat or maize, soya, certain millets or pulses. These differences have been reproduced in animal peptic ulcer models. Using these models it has been shown that the protective factor against ulceration lies in the lipid fraction present in staple foods from the low prevalence areas. The lipid fraction not only gave protection in the experimental models against ulceration but also promoted healing. The pulse Dolichos biflorus (horse gram) gave the greatest yield of the lipid and this was used for further investigations. It was found that the ulceroprotective activity of the lipid lay in its phospholipid and sterols fractions. The presence or absence of protective lipid in the diet would account for the regional differences in duodenal ulcer prevalence.
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Kate V, Ananthakrishnan N, Tovey FI. Is Helicobacter pylori Infection the Primary Cause of Duodenal Ulceration or a Secondary Factor? A Review of the Evidence. Gastroenterol Res Pract 2013; 2013:425840. [PMID: 23606834 PMCID: PMC3623110 DOI: 10.1155/2013/425840] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2013] [Accepted: 03/07/2013] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) has a role in the multifactorial etiology of peptic ulcer disease. A link between H. pylori infection and duodenal ulcer disease is now established. Other contributing factors and their interaction with the organism may initiate the ulcerative process. The fact that eradication of H. pylori infection leads to a long-term cure in the majority of duodenal ulcer patients and the fact that the prevalence of infection is higher in ulcer patients than in the normal population are cogent arguments in favor of it being the primary cause of the ulceration. Against this concept there are issues that need explanation such as the reason why only a minority of infected persons develop duodenal ulceration when infection with H. pylori is widespread. There is evidence that H. pylori infection has been prevalent for several centuries, yet duodenal ulceration became common at the beginning of the twentieth century. The prevalence of duodenal ulceration is not higher in countries with a high prevalence of H. pylori infection. This paper debate puts forth the point of view of two groups of workers in this field whether H. pylori infection is the primary cause of duodenal ulcer disease or a secondary factor.
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Affiliation(s)
- Vikram Kate
- Department of General and Gastrointestinal Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry 605006, India
| | - N. Ananthakrishnan
- Mahatma Gandhi Medical College & Research Institute, Pondicherry 607402, India
| | - Frank I. Tovey
- Division of Surgery and Interventional Science, University College London, London W1W 7ET, UK
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Tovey FI, Bardhan KD, Hobsley M. Dietary phosphilipids and sterols protective against peptic ulceration. Phytother Res 2012; 27:1265-9. [PMID: 23097339 DOI: 10.1002/ptr.4865] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2012] [Revised: 09/23/2012] [Accepted: 09/27/2012] [Indexed: 12/16/2022]
Abstract
The prevalence of duodenal ulceration in regions of developing countries with a stable diet is related to the staple food(s) in that diet. A higher prevalence occurs in areas where the diet is principally milled rice, refined wheat or maize, yams, cassava, sweet potato or green bananas, and a lower prevalence in areas where the staple diet is based on unrefined wheat or maize, soya, certain millets or certain pulses. Experiments using animal peptic ulcer models showed that the lipid fraction in foods from the staple diets of low prevalence areas gave protection against both gastric and duodenal ulceration, including ulceration due to non-steroidal anti-inflammatory drugs (NSAIDs), and also promoted healing of ulceration. The protective activity was found to lie in the phospholipid, sterol and sterol ester fractions of the lipid. Amongst individual phospholipids present in the phospholipid fraction, phosphatidyl ethanolamine (cephalin) and phosphatidyl choline (Lecithin) predominated. The sterol fraction showing activity contained β-sitosterol, stigmasterol and an unidentified isomer of β-sitosterol. The evidence shows that dietary phytosterols and phospholipids, both individually and in combination, have a protective effect on gastroduodenal mucosa. These findings may prove to be important in the prevention and management of duodenal and gastric ulceration including ulceration due to NSAIDs.
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Affiliation(s)
- F I Tovey
- Division of Surgery and Interventional Science, University College, London, UK.
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Ma LS. A tribute to Dr. Frank I Tovey on his 90th birthday. World J Gastroenterol 2011; 17:3565-6. [PMID: 21987600 PMCID: PMC3180010 DOI: 10.3748/wjg.v17.i31.3565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2011] [Revised: 08/11/2011] [Accepted: 08/14/2011] [Indexed: 02/06/2023] Open
Abstract
This paper pays a tribute to Dr. Frank I Tovey on his 90th birthday which happens on September 1, 2011, and briefly describes the major findings in his research career and contributions as follows. The geographical prevalence of duodenal ulceration is related to staple diets. Unrefined wheat and maize, soya, certain pulses and millets are associated with a low prevalence while refined wheat, maize and rice, yams, cassava and green banana with a high prevalence. Predominant foodstuffs from low prevalence areas are ulceroprotective in rat peptic ulcer models. The protective activity lies in the lipid fraction present in these foodstuffs. The lipid fraction also promotes ulcer healing, is active both orally and intramuscularly and is ulceroprotective against non-steroidal anti-inflammatory drugs (NSAIDs). The phospholipids and phytosterols present in the lipid have been identified to be responsible for this protective activity. The combination of phospholipids and phytosterols may be of value in the prevention and treatment of duodenal ulceration and protection against the ulcerogenic effect of NSAIDs.
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Tovey FI, Capanoglu D, Langley GJ, Herniman JM, Bor S, Ozutemiz O, Hobsley M, Bardhan KD, Linclau B. Dietary Phytosterols Protective Against Peptic Ulceration. Gastroenterology Res 2011; 4:149-156. [PMID: 27942332 PMCID: PMC5139726 DOI: 10.4021/gr328w] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/04/2011] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND In developing countries the prevalence of duodenal ulceration is related to the staple diet and not to the prevalence of Helicobacter pylori. Experiments using animal peptic ulcer models show that the lipid fraction in foods from the staple diets of low prevalence areas gives protection against ulceration, including ulceration due to non-steroidal anti-inflammatory drugs (NSAIDs), and also promotes healing of ulceration. The lipid from the pulse Dolichos biflorus (Horse gram) was highly active and used for further investigations. Further experiments showed the phospholipids, sterol esters and sterols present in Horse gram lipid were gastroprotective. Dietary phospholipids are known to be protective, but the nature of protective sterols in staple diets is not known. The present research investigates the nature of the protective phytosterols. METHODS Sterol fractions were extracted from the lipid in Dolichos biflorus and tested for gastroprotection using the rat ethanol model. The fractions showing protective activity were isolated and identification of the components was investigated by Gas Chromatography-Mass Spectrometry (GC-MS). RESULTS The protective phytosterol fraction was shown to consist of stigmasterol, β-sitosterol and a third as yet unidentified sterol, isomeric with β-sitosterol. CONCLUSIONS Dietary changes, affecting the intake of protective phospholipids and phytosterols, may reduce the prevalence of duodenal ulceration in areas of high prevalence and may reduce the incidence of recurrent duodenal ulceration after healing and elimination of Helicobacter pylori infection. A combination of phospholipids and phytosterols, such as found in the lipid fraction of ulceroprotecive foods, may be of value in giving protection against the ulcerogenic effect of NSAIDs.
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Affiliation(s)
- Frank I Tovey
- Division of Surgery and Interventional Science, University College, London, UK
| | - Doga Capanoglu
- Department of Gastroenterology, Ege University, Bornova, Turkey
| | | | | | - Serhat Bor
- Department of Gastroenterology, Ege University, Bornova, Turkey
| | - Omer Ozutemiz
- Department of Gastroenterology, Ege University, Bornova, Turkey
| | - Michael Hobsley
- Division of Surgery and Interventional Science, University College, London, UK
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Abstract
PUD affects both the East and the West. The magnitude of the problem, however, varies within these regions. The study of peptic ulcer epidemiology is impeded by the paucity of general population-based data, invasiveness of diagnostic tests, and variable access to testing facilities. As such, direct comparisons of PUD epidemiology between the East and the West are difficult. The prevalence rates of H pylori are highly variable and depend greatly on the local sanitation conditions. The use of NSAIDs and aspirin is ubiquitous and increasing especially for the antiplatelet activity of aspirin in the prophylaxis of cardiovascular events. There is evidence that pharmacogenetics play a role in susceptibility to the ulcerogenic properties of NSAIDs. The prevalence of PUD parallels the risk factors, but emerging in both the East and the West is idiopathic PUD, now a substantial proportion of ulcers in areas of declining H pylori infection. Genetic polymorphisms affect the efficacy of treatment using PPIs. Local H pylori resistance rates also influence the eradication success rates.
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Affiliation(s)
- Rupert W Leong
- Concord Hospital, Ambulatory Care Endoscopy Unit, Level 1 West, Hospital Road, Concord, Sydney NSW 2139, Australia.
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Controversies in the Helicobacter pylori/duodenal ulcer story. Trans R Soc Trop Med Hyg 2008; 102:1171-5. [PMID: 18589464 DOI: 10.1016/j.trstmh.2008.04.035] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2008] [Revised: 04/24/2008] [Accepted: 04/24/2008] [Indexed: 12/12/2022] Open
Abstract
In patients with Helicobacter pylori-positive duodenal ulcer (DU), the organism must be eradicated to achieve rapid, stable healing. However, evidence is against much else that is commonly accepted. (1) Does H. pylori cause the ulcer? Evidence against includes archaeopathology, geographical prevalence, temporal relationships and H. pylori-negative DU patients. DU can recur after eradication of H. pylori infection, and DUs may remain healed after reduction of acid secretion despite persistent infection. The faster healing of ulcers when H. pylori has been eradicated is due to the organism's interference with neoangiogenesis and the healing of wounded epithelial cells. (2) Does H. pylori infection persist until pharmacologically eradicated? Studies based on current infection show that H. pylori infection is a labile state that can change in 3 months. High rates of gastric acid secretion result in spontaneous cure, whereas low rates permit re-infection. Hydrochloric acid, necessary for producing a DU, is strongly associated with the likelihood of an ulcer. At the start, patients owe their ulcer to gastric hypersecretion of hydrochloric acid; approximately 60% may be H. pylori-negative. If acid is suppressed, the less acid milieu encourages invasion by H. pylori, especially if the strain is virulent.
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Abstract
The facts that H pylori infection is commoner in duodenal ulcer (DU) patients than in the normal population, and that eradication results in most cases being cured, have led to the belief that it causes DU. However, early cases of DU are less likely than established ones to be infected. H pylori-negative cases are usually ascribed to specific associated factors such as non-steroidal anti-inflammatory drugs (NSAIDs), Crohn’s disease, and hypergastrinaemia, but even after excluding these, several H pylori-negative cases remain and are particularly common in areas of low prevalence of H pylori infection. Moreover, this incidence of H pylori negative DU is not associated with a fall in overall DU prevalence when compared with countries with a higher H pylori prevalence. In countries with a high H pylori prevalence there are regional differences in DU prevalence, but no evidence of an overall higher prevalence of DU than in countries with a low H pylori prevalence. There is no evidence that virulence factors are predictive of clinical outcome. After healing following eradication of H pylori infection DU can still recur. Medical or surgical measures to reduce acid output can lead to long-term healing despite persistence of H pylori infection. Up to half of cases of acute DU perforation are H pylori negative. These findings lead to the conclusion that H pylori infection does not itself cause DU, but leads to resistance to healing, i.e., chronicity. This conclusion is shown not to be incompatible with the universally high prevalence of DU compared with controls.
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Affiliation(s)
- Michael Hobsley
- Department of Surgery, Royal Free and University College Medical School, London, United Kingdom.
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Abstract
BACKGROUND In South Africa there is suggestive evidence that home-pounded maize protects against duodenal ulceration. Therefore the purpose of the present paper was to test, in an animal model, whether oil from home-pounded maize gives protection against ulceration and whether this effect is present in commercially prepared maize oil. METHODS Gastric ulceration was induced in rats with topical ethanol 1 h after giving oil prepared either from fresh-pounded or from commercially treated maize. The lengths of the linear ulcers produced were measured with a planimeter and summed in each rat. Control observations were made using arachis oil (which is known not to be ulceroprotective) and horse gram lipid (which is known to be strongly ulceroprotective). Statistical comparisons were performed mainly with the Mann-Whitney U-test, but also with reference to the normal distribution. Thin-layer chromatography (TLC) was performed on the oil from fresh maize, and the fractions similarly investigated for ulceroprotective activity. RESULTS Fresh maize oil was strongly ulceroprotective (P = 0.0039), commercial maize oil was not (P = 0.2864). The active ingredient in the fresh maize oil was located in the fraction near the solvent front. CONCLUSION These findings support the hypothesis that home-pounded maize protects against duodenal ulceration.
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Affiliation(s)
- Frank I Tovey
- Department of Surgery, University College London, London, UK.
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Berger A, Jones PJH, Abumweis SS. Plant sterols: factors affecting their efficacy and safety as functional food ingredients. Lipids Health Dis 2004; 3:5. [PMID: 15070410 PMCID: PMC419367 DOI: 10.1186/1476-511x-3-5] [Citation(s) in RCA: 160] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2004] [Accepted: 04/07/2004] [Indexed: 11/10/2022] Open
Abstract
Plant sterols are naturally occurring molecules that humanity has evolved with. Herein, we have critically evaluated recent literature pertaining to the myriad of factors affecting efficacy and safety of plant sterols in free and esterified forms. We conclude that properly solubilized 4-desmetyl plant sterols, in ester or free form, in reasonable doses (0.8-1.0 g of equivalents per day) and in various vehicles including natural sources, and as part of a healthy diet and lifestyle, are important dietary components for lowering low density lipoprotein (LDL) cholesterol and maintaining good heart health. In addition to their cholesterol lowering properties, plant sterols possess anti-cancer, anti-inflammatory, anti-atherogenicity, and anti-oxidation activities, and should thus be of clinical importance, even for those individuals without elevated LDL cholesterol. The carotenoid lowering effect of plant sterols should be corrected by increasing intake of food that is rich in carotenoids. In pregnant and lactating women and children, further study is needed to verify the dose required to decrease blood cholesterol without affecting fat-soluble vitamins and carotenoid status.
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Affiliation(s)
- Alvin Berger
- Head, Biochemical Profiling, Paradigm Genetics, P.O. Box 14528, Research Triangle Park, North Carolina, 27709-4528, USA
| | - Peter JH Jones
- School of Dietetics and Human Nutrition, McGill University, 21,111 Lakeshore Road, Ste-Anne-de-Bellevue, Quebec, H9X3V9, Canada
| | - Suhad S Abumweis
- School of Dietetics and Human Nutrition, McGill University, 21,111 Lakeshore Road, Ste-Anne-de-Bellevue, Quebec, H9X3V9, Canada
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