Metabiotic extracted from Bifidobacterium bifidum modulates antioxidant capacity and inflammatory responses during peptic ulcer healing in male wistar rats: a preliminary study
,
Abstract
Background and Objectives: Peptic ulcer disease is a multifactorial disease that affects up to 10% of people. The use of natural product remedies has received much attention for its treatment. In this research, the healing effect of metabiotic extracted from Bifidobacterium bifidum was investigated.
Materials and Methods: 45 male wistar rats were divided into 3 groups (Ctrl-, drug, and metabiotic), and stomach ulcers were induced by ethanol administration and treated by drug and metabiotic. The healing process was investigated on different days by histological analysis and qRT-PCR.
Results: The metabiotic increased IL-8 and PDGF expression and stimulated the recruitment of polymorphonuclear cells to the wound site. It caused a faster onset of the inflammation phase followed by the proliferation phase. The metabiotic increased the expression of SOD and GPx genes and the antioxidant capacity of the wound. The increase in EGF expression led to faster re-epithelization, which was evident in the wound closure process.
Conclusion: Metabiotic extracted from B. bifidum is a promising candidate for the treatment of PUD. It causes a faster onset of the inflammation phase. Improving the antioxidant status of the wound, causes a faster resolution of inflammation, which leads to the acceleration of the wound-healing process.
1. Xie X, Ren K, Zhou Z, Dang C, Zhang H. The global, regional and national burden of peptic ulcer disease from 1990 to 2019: a population-based study. BMC Gastroenterol 2022; 22: 58.
2. Lanas A, Dumonceau J-M, Hunt RH, Fujishiro M, Scheiman JM, Gralnek IM, et al. Non-variceal upper gastrointestinal bleeding. Nat Rev Dis Primers 2018; 4: 18020.
3. Sumbul S, Ahmad MA, Mohd A, Mohd A. Role of phenolic compounds in peptic ulcer: An overview. J Pharm Bioallied Sci 2011; 3: 361-367.
4. Nagasue T, Nakamura S, Kochi S, Kurahara K, Yaita H, Kawasaki K, et al. Time trends of the impact of Helicobacter pylori infection and nonsteroidal anti-inflammatory drugs on peptic ulcer bleeding in Japanese patients. Digestion 2015; 91: 37-41.
5. Nagata N, Niikura R, Sekine K, Sakurai T, Shimbo T, Kishida Y, et al. Risk of peptic ulcer bleeding associated with H elicobacter pylori infection, nonsteroidal anti‐inflammatory drugs, low‐dose aspirin, and antihypertensive drugs: A case‐control study. J Gastroenterol Hepatol 2015; 30: 292-298.
6. Robinson K, Letley DP, Kaneko K. The human stomach in health and disease: infection strategies by Helicobacter pylori. Curr Top Microbiol Immunol 2017; 400: 1-26.
7. Mohseni S, Bayani M, Bahmani F, Tajabadi-Ebrahimi M, Bayani MA, Jafari P, et al. The beneficial effects of probiotic administration on wound healing and metabolic status in patients with diabetic foot ulcer: a randomized, double‐blind, placebo‐controlled trial. Diabetes Metab Res Rev 2018; 34: 10.1002/dmrr.2970.
8. Long AT, Kenne E, Jung R, Fuchs TA, Renné T. Contact system revisited: an interface between inflammation, coagulation, and innate immunity. J Thromb Haemost 2016; 14: 427-437.
9. Smith SA, Travers RJ, Morrissey JH. How it all starts: Initiation of the clotting cascade. Crit Rev Biochem Mol Biol 2015; 50: 326-336.
10. Tarnawski AS. Cellular and molecular mechanisms of gastrointestinal ulcer healing. Dig Dis Sci 2005; 50 Suppl 1: S24-33.
11. Jamaran S, Jafari P, Marjani A, Akbari N, Feizabad MM. Novel wound dressing based on postbiotic/chitosan film accelerates cutaneous wound healing. Jundishapur J Microbiol 2021; 14(12): e120806.
12. Auf Dem Keller U, Kümin A, Braun S, Werner S. Reactive oxygen species and their detoxification in healing skin wounds. J Investig Dermatol Symp Proc 2006; 11: 106-111.
13. Schieber M, Chandel NS. ROS function in redox signaling and oxidative stress. Curr Biol 2014; 24: R453-62.
14. Zhu G, Wang Q, Lu S, Niu Y. Hydrogen peroxide: a potential wound therapeutic target. Med Princ Pract 2017; 26: 301-308.
15. Sies H, Jones DP. Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat Rev Mol Cell Biol 2020; 21: 363-383.
16. Mirończuk-Chodakowska I, Witkowska AM, Zujko ME. Endogenous non-enzymatic antioxidants in the human body. Adv Med Sci 2018; 63: 68-78.
17. Belinskaia DA, Voronina PA, Shmurak VI, Vovk MA, Batalova AA, Jenkins RO, et al. The universal soldier: Enzymatic and non-enzymatic antioxidant functions of serum albumin. Antioxidants (Basel) 2020; 9: 966.
18. Ighodaro OM, Akinloye OA. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alexandria J Med 2018; 54: 287-293.
19. Kurahashi T, Fujii J. Roles of antioxidative enzymes in wound healing. J Dev Biol 2015; 3: 57-70.
20. Nafiu AB, Rahman MT. Anti-inflammatory and antioxidant properties of unripe papaya extract in an excision wound model. Pharm Biol 2015; 53: 662-671.
21. Wang Y, Wu Y, Wang Y, Xu H, Mei X, Yu D, et al. Antioxidant properties of probiotic bacteria. Nutrients 2017; 9: 521.
22. Libera J, Latoch A, Wójciak KM. Utilization of grape seed extract as a natural antioxidant in the technology of meat products inoculated with a probiotic strain of LAB. Foods 2020; 9: 103.
23. Feng T, Wang J. Oxidative stress tolerance and antioxidant capacity of lactic acid bacteria as probiotic: A systematic review. Gut Microbes 2020; 12: 1801944.
24. Kim H, Kim J-S, Kim YG, Jeong Y, Kim J-E, Paek N-S, et al. Antioxidant and probiotic properties of Lactobacilli and Bifidobacteria of human origins. Biotechnol Bioprocess Eng 2020; 25: 421-430.
25. Happel AU, Barnabas SL, Froissart R, Passmore JS. Weighing in on the risks and benefits of probiotic use in HIV-infected and immunocompromised populations. Benef Microbes 2018; 9: 239-246.
26. Haghighat L, Crum-Cianflone NF. The potential risks of probiotics among HIV-infected persons: Bacteraemia due to Lactobacillus acidophilus and review of the literature. Int J STD AIDS 2016; 27: 1223-1230.
27. Ferrario C, Duranti S, Milani C, Mancabelli L, Lugli GA, Turroni F, et al. Exploring amino acid auxotrophy in bifidobacterium bifidum PRL2010. Front Microbiol 2015; 6: 1331.
28. Guzmán-Gómez O, García-Rodríguez RV, Quevedo-Corona L, Pérez-Pastén-Borja R, Rivero-Ramírez NL, Ríos-Castro E, et al. Amelioration of ethanol-induced gastric ulcers in rats pretreated with phycobiliproteins of Arthrospira (Spirulina) Maxima. Nutrients 2018; 10: 763.
29. sowjanya A, Pal A. Drug-Drug-Dietary interactions in pharmacotherapy of GIT medication: A review. Int J Res Pharm Sci 2020; 11: 2903-2909.
30. Subudhi BB, Sahoo SP, Sahu PK. Updates in Drug Development strategies against peptic ulcer. J Gastrointest Dig Syst 2016; 6: 10.4172/2161-069X.1000398.
31. Wellington D, Mikaelian I, Singer L. Comparison of ketamine–xylazine and ketamine–dexmedetomidine anesthesia and intraperitoneal tolerance in rats. J Am Assoc Lab Anim Sci 2013; 52: 481-487.
32. Beeton C, Garcia A, Chandy KG. Drawing blood from rats through the saphenous vein and by cardiac puncture. J Vis Exp 2007; (7): 266.
33. El-Ela FIA, Farghali AA, Mahmoud RK, Mohamed NA, Moaty SAA. New approach in ulcer prevention and wound healing treatment using doxycycline and amoxicillin/LDH Nanocomposites. Sci Rep 2019; 9: 6418.
34. Feldman AT, Wolfe D. Tissue processing and hematoxylin and eosin staining. Methods Mol Biol 2014; 1180: 31-43.
35. Fischer AH, Jacobson KA, Rose J, Zeller R. Hematoxylin and eosin staining of tissue and cell sections. CSH Protoc 2008; 2008: pdb.prot4986.
36. Gonzalez AC, Costa TF, Andrade ZA, Medrado AR. Wound healing-A literature review. An Bras Dermatol 2016; 91; 614-620.
37. Rodriguez PG, Felix FN, Woodley DT, Shim EK. The role of oxygen in wound healing: a review of the literature. Dermatol Surg 2008; 34: 1159-1169.
38. Kimmel HM, Grant A, Ditata J. The Presence of Oxygen in Wound Healing. Wounds 2016; 28: 264-270.
39. Velnar T, Bailey T, Smrkolj V. The wound healing process: an overview of the cellular and molecular mechanisms. J Int Med Res 2009; 37: 1528-1542.
40. Dunnill C, Patton T, Brennan J, Barrett J, Dryden M, Cooke J, et al. Reactive oxygen species (ROS) and wound healing: the functional role of ROS and emerging ROS‐modulating technologies for augmentation of the healing process. Int Wound J 2017; 14: 89-96.
41. Nouvong A, Ambrus AM, Zhang ER, Hultman L, Coller HA. Reactive oxygen species and bacterial biofilms in diabetic wound healing. Physiol Genomics 2016; 48: 889-896.
42. Xu Z, Han S, Gu Z, Wu J. Advances and impact of antioxidant hydrogel in chronic wound healing. Adv Healthc Mater 2020; 9(5): e1901502.
43. Li Z, Zhang J, Fu Y, Yang L, Zhu F, Liu X, et al. Antioxidant shape amphiphiles for accelerated wound healing. J Mater Chem B 2020; 8: 7018-7023.
44. Amaretti A, di Nunzio M, Pompei A, Raimondi S, Rossi M, Bordoni A. Antioxidant properties of potentially probiotic bacteria: in vitro and in vivo activities. Appl Microbiol Biotechnol 2013; 97: 809-817.
45. Gentile P, Garcovich S. Systematic review: adipose-derived mesenchymal stem cells, platelet-rich plasma and biomaterials as new regenerative strategies in chronic skin wounds and soft tissue defects. Int J Mol Sci 2021; 22: 1538.
46. Finnson KW, Arany PR, Philip A. Transforming growth factor beta signaling in cutaneous wound healing: lessons learned from animal studies. Adv Wound Care (New Rochelle) 2013; 2: 225-237.
47. Cakir SN, Whitehead KM, Hendricks HKL, de Castro Brás LE. Novel techniques targeting fibroblasts after ischemic heart injury. Cells 2022; 11: 402.
48. Ellis S, Lin EJ, Tartar D. Immunology of wound healing. Curr Dermatol Rep 2018; 7: 350-358.
49. D'Arpa P, Leung KP. Toll-like receptor signaling in burn wound healing and scarring. Adv Wound Care (New Rochelle) 2017; 6: 330-343.
50. Shen Q, Shang N, Li P. In vitro and in vivo antioxidant activity of Bifidobacterium animalis 01 isolated from centenarians. Curr Microbiol 2011; 62: 1097-1103.
51. Lee J, Hwang K-T, Chung M-Y, Cho D-H, Park C-S. Resistance of Lactobacillus casei KCTC 3260 to reactive oxygen species (ROS): role for a metal ion chelating effect. J Food Sci 2005; 70: m388-m391.
52. Ahire JJ, Mokashe NU, Patil HJ, Chaudhari BL. Antioxidative potential of folate producing probiotic Lactobacillus helveticus CD6. J Food Sci Technol 2013; 50: 26-34.
53. Silva YP, Bernardi A, Frozza RL. The role of short-chain fatty acids from gut microbiota in gut-brain communication. Front Endocrinol (Lausanne) 2020; 11: 25.
54. Kim S, Park S, Choi TG, Kim SS. Role of short chain Fatty acids in epilepsy and potential benefits of probiotics and prebiotics: targeting “Health” of Epileptic Patients. Nutrients 2022; 14: 2982.
55. Lee JY, Kang C-H. Probiotics Alleviate Oxidative Stress in H2O2-exposed Hepatocytes and t-BHP-Induced C57BL/6 Mice. Microorganisms 2022; 10: 234.
2. Lanas A, Dumonceau J-M, Hunt RH, Fujishiro M, Scheiman JM, Gralnek IM, et al. Non-variceal upper gastrointestinal bleeding. Nat Rev Dis Primers 2018; 4: 18020.
3. Sumbul S, Ahmad MA, Mohd A, Mohd A. Role of phenolic compounds in peptic ulcer: An overview. J Pharm Bioallied Sci 2011; 3: 361-367.
4. Nagasue T, Nakamura S, Kochi S, Kurahara K, Yaita H, Kawasaki K, et al. Time trends of the impact of Helicobacter pylori infection and nonsteroidal anti-inflammatory drugs on peptic ulcer bleeding in Japanese patients. Digestion 2015; 91: 37-41.
5. Nagata N, Niikura R, Sekine K, Sakurai T, Shimbo T, Kishida Y, et al. Risk of peptic ulcer bleeding associated with H elicobacter pylori infection, nonsteroidal anti‐inflammatory drugs, low‐dose aspirin, and antihypertensive drugs: A case‐control study. J Gastroenterol Hepatol 2015; 30: 292-298.
6. Robinson K, Letley DP, Kaneko K. The human stomach in health and disease: infection strategies by Helicobacter pylori. Curr Top Microbiol Immunol 2017; 400: 1-26.
7. Mohseni S, Bayani M, Bahmani F, Tajabadi-Ebrahimi M, Bayani MA, Jafari P, et al. The beneficial effects of probiotic administration on wound healing and metabolic status in patients with diabetic foot ulcer: a randomized, double‐blind, placebo‐controlled trial. Diabetes Metab Res Rev 2018; 34: 10.1002/dmrr.2970.
8. Long AT, Kenne E, Jung R, Fuchs TA, Renné T. Contact system revisited: an interface between inflammation, coagulation, and innate immunity. J Thromb Haemost 2016; 14: 427-437.
9. Smith SA, Travers RJ, Morrissey JH. How it all starts: Initiation of the clotting cascade. Crit Rev Biochem Mol Biol 2015; 50: 326-336.
10. Tarnawski AS. Cellular and molecular mechanisms of gastrointestinal ulcer healing. Dig Dis Sci 2005; 50 Suppl 1: S24-33.
11. Jamaran S, Jafari P, Marjani A, Akbari N, Feizabad MM. Novel wound dressing based on postbiotic/chitosan film accelerates cutaneous wound healing. Jundishapur J Microbiol 2021; 14(12): e120806.
12. Auf Dem Keller U, Kümin A, Braun S, Werner S. Reactive oxygen species and their detoxification in healing skin wounds. J Investig Dermatol Symp Proc 2006; 11: 106-111.
13. Schieber M, Chandel NS. ROS function in redox signaling and oxidative stress. Curr Biol 2014; 24: R453-62.
14. Zhu G, Wang Q, Lu S, Niu Y. Hydrogen peroxide: a potential wound therapeutic target. Med Princ Pract 2017; 26: 301-308.
15. Sies H, Jones DP. Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat Rev Mol Cell Biol 2020; 21: 363-383.
16. Mirończuk-Chodakowska I, Witkowska AM, Zujko ME. Endogenous non-enzymatic antioxidants in the human body. Adv Med Sci 2018; 63: 68-78.
17. Belinskaia DA, Voronina PA, Shmurak VI, Vovk MA, Batalova AA, Jenkins RO, et al. The universal soldier: Enzymatic and non-enzymatic antioxidant functions of serum albumin. Antioxidants (Basel) 2020; 9: 966.
18. Ighodaro OM, Akinloye OA. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alexandria J Med 2018; 54: 287-293.
19. Kurahashi T, Fujii J. Roles of antioxidative enzymes in wound healing. J Dev Biol 2015; 3: 57-70.
20. Nafiu AB, Rahman MT. Anti-inflammatory and antioxidant properties of unripe papaya extract in an excision wound model. Pharm Biol 2015; 53: 662-671.
21. Wang Y, Wu Y, Wang Y, Xu H, Mei X, Yu D, et al. Antioxidant properties of probiotic bacteria. Nutrients 2017; 9: 521.
22. Libera J, Latoch A, Wójciak KM. Utilization of grape seed extract as a natural antioxidant in the technology of meat products inoculated with a probiotic strain of LAB. Foods 2020; 9: 103.
23. Feng T, Wang J. Oxidative stress tolerance and antioxidant capacity of lactic acid bacteria as probiotic: A systematic review. Gut Microbes 2020; 12: 1801944.
24. Kim H, Kim J-S, Kim YG, Jeong Y, Kim J-E, Paek N-S, et al. Antioxidant and probiotic properties of Lactobacilli and Bifidobacteria of human origins. Biotechnol Bioprocess Eng 2020; 25: 421-430.
25. Happel AU, Barnabas SL, Froissart R, Passmore JS. Weighing in on the risks and benefits of probiotic use in HIV-infected and immunocompromised populations. Benef Microbes 2018; 9: 239-246.
26. Haghighat L, Crum-Cianflone NF. The potential risks of probiotics among HIV-infected persons: Bacteraemia due to Lactobacillus acidophilus and review of the literature. Int J STD AIDS 2016; 27: 1223-1230.
27. Ferrario C, Duranti S, Milani C, Mancabelli L, Lugli GA, Turroni F, et al. Exploring amino acid auxotrophy in bifidobacterium bifidum PRL2010. Front Microbiol 2015; 6: 1331.
28. Guzmán-Gómez O, García-Rodríguez RV, Quevedo-Corona L, Pérez-Pastén-Borja R, Rivero-Ramírez NL, Ríos-Castro E, et al. Amelioration of ethanol-induced gastric ulcers in rats pretreated with phycobiliproteins of Arthrospira (Spirulina) Maxima. Nutrients 2018; 10: 763.
29. sowjanya A, Pal A. Drug-Drug-Dietary interactions in pharmacotherapy of GIT medication: A review. Int J Res Pharm Sci 2020; 11: 2903-2909.
30. Subudhi BB, Sahoo SP, Sahu PK. Updates in Drug Development strategies against peptic ulcer. J Gastrointest Dig Syst 2016; 6: 10.4172/2161-069X.1000398.
31. Wellington D, Mikaelian I, Singer L. Comparison of ketamine–xylazine and ketamine–dexmedetomidine anesthesia and intraperitoneal tolerance in rats. J Am Assoc Lab Anim Sci 2013; 52: 481-487.
32. Beeton C, Garcia A, Chandy KG. Drawing blood from rats through the saphenous vein and by cardiac puncture. J Vis Exp 2007; (7): 266.
33. El-Ela FIA, Farghali AA, Mahmoud RK, Mohamed NA, Moaty SAA. New approach in ulcer prevention and wound healing treatment using doxycycline and amoxicillin/LDH Nanocomposites. Sci Rep 2019; 9: 6418.
34. Feldman AT, Wolfe D. Tissue processing and hematoxylin and eosin staining. Methods Mol Biol 2014; 1180: 31-43.
35. Fischer AH, Jacobson KA, Rose J, Zeller R. Hematoxylin and eosin staining of tissue and cell sections. CSH Protoc 2008; 2008: pdb.prot4986.
36. Gonzalez AC, Costa TF, Andrade ZA, Medrado AR. Wound healing-A literature review. An Bras Dermatol 2016; 91; 614-620.
37. Rodriguez PG, Felix FN, Woodley DT, Shim EK. The role of oxygen in wound healing: a review of the literature. Dermatol Surg 2008; 34: 1159-1169.
38. Kimmel HM, Grant A, Ditata J. The Presence of Oxygen in Wound Healing. Wounds 2016; 28: 264-270.
39. Velnar T, Bailey T, Smrkolj V. The wound healing process: an overview of the cellular and molecular mechanisms. J Int Med Res 2009; 37: 1528-1542.
40. Dunnill C, Patton T, Brennan J, Barrett J, Dryden M, Cooke J, et al. Reactive oxygen species (ROS) and wound healing: the functional role of ROS and emerging ROS‐modulating technologies for augmentation of the healing process. Int Wound J 2017; 14: 89-96.
41. Nouvong A, Ambrus AM, Zhang ER, Hultman L, Coller HA. Reactive oxygen species and bacterial biofilms in diabetic wound healing. Physiol Genomics 2016; 48: 889-896.
42. Xu Z, Han S, Gu Z, Wu J. Advances and impact of antioxidant hydrogel in chronic wound healing. Adv Healthc Mater 2020; 9(5): e1901502.
43. Li Z, Zhang J, Fu Y, Yang L, Zhu F, Liu X, et al. Antioxidant shape amphiphiles for accelerated wound healing. J Mater Chem B 2020; 8: 7018-7023.
44. Amaretti A, di Nunzio M, Pompei A, Raimondi S, Rossi M, Bordoni A. Antioxidant properties of potentially probiotic bacteria: in vitro and in vivo activities. Appl Microbiol Biotechnol 2013; 97: 809-817.
45. Gentile P, Garcovich S. Systematic review: adipose-derived mesenchymal stem cells, platelet-rich plasma and biomaterials as new regenerative strategies in chronic skin wounds and soft tissue defects. Int J Mol Sci 2021; 22: 1538.
46. Finnson KW, Arany PR, Philip A. Transforming growth factor beta signaling in cutaneous wound healing: lessons learned from animal studies. Adv Wound Care (New Rochelle) 2013; 2: 225-237.
47. Cakir SN, Whitehead KM, Hendricks HKL, de Castro Brás LE. Novel techniques targeting fibroblasts after ischemic heart injury. Cells 2022; 11: 402.
48. Ellis S, Lin EJ, Tartar D. Immunology of wound healing. Curr Dermatol Rep 2018; 7: 350-358.
49. D'Arpa P, Leung KP. Toll-like receptor signaling in burn wound healing and scarring. Adv Wound Care (New Rochelle) 2017; 6: 330-343.
50. Shen Q, Shang N, Li P. In vitro and in vivo antioxidant activity of Bifidobacterium animalis 01 isolated from centenarians. Curr Microbiol 2011; 62: 1097-1103.
51. Lee J, Hwang K-T, Chung M-Y, Cho D-H, Park C-S. Resistance of Lactobacillus casei KCTC 3260 to reactive oxygen species (ROS): role for a metal ion chelating effect. J Food Sci 2005; 70: m388-m391.
52. Ahire JJ, Mokashe NU, Patil HJ, Chaudhari BL. Antioxidative potential of folate producing probiotic Lactobacillus helveticus CD6. J Food Sci Technol 2013; 50: 26-34.
53. Silva YP, Bernardi A, Frozza RL. The role of short-chain fatty acids from gut microbiota in gut-brain communication. Front Endocrinol (Lausanne) 2020; 11: 25.
54. Kim S, Park S, Choi TG, Kim SS. Role of short chain Fatty acids in epilepsy and potential benefits of probiotics and prebiotics: targeting “Health” of Epileptic Patients. Nutrients 2022; 14: 2982.
55. Lee JY, Kang C-H. Probiotics Alleviate Oxidative Stress in H2O2-exposed Hepatocytes and t-BHP-Induced C57BL/6 Mice. Microorganisms 2022; 10: 234.
| Files | ||
| Issue | Vol 15 No 1 (2023) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v15i1.11924 | |
| Keywords | ||
| Bifidobacterium bifidum; Metabiotic; Peptic ulcer; Inflammation; Antioxidant | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Almasyan R, Jafari P, Farjanikish G, Noorbazargan H. Metabiotic extracted from Bifidobacterium bifidum modulates antioxidant capacity and inflammatory responses during peptic ulcer healing in male wistar rats: a preliminary study. Iran J Microbiol. 2023;15(1):102-110.
