open access
Evaluation of butyric acid as a potential supportive treatment in anterior uveitis
, 1, 2, 2, 3, 2, 1
Affiliations- Ophthalmology Department, Military Institute of Medicine, Warsaw, Poland
- Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland
- Department of Pathology and Veterinary Diagnostics, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, Poland
open access
Abstract
Background: The aim of the study was to evaluate the anti-inflammatory effect of topically administered aqueous sodium butyrate solution in an endotoxin-induced uveitis rat model and compare the results with corticosteroid treatment.
Material and methods: Forty female Lewis rats were randomly divided into five groups. Uveitis was induced by a single lipopolysaccharide (LPS) injection into each footpad of each LPS+ rat. Group I (naive) received saline injected into the footpad of each rat at a dose of 0.1 mL/each footpad; Group II (LPS+) received saline solution topically. Group III (LPS+ Dex) — an aqueous dexamethasone sodium phosphate solution topically; Group IV (LPS+ But 0.5 mM) — 0.5 mM aqueous sodium butyrate solution topically, Group V (LPS+ But 1 mM) — 1.0 mM aqueous sodium butyrate solution topically. Clinical scoring of inflammation in rat eyes was evaluated before LPS injection and after 24 hours. The iris involvement, posterior synechiae presence, and insight into the eye fundus were clinicallyassessed. A histopathological examination was also performed. The rats were euthanatized 24 hours after LPS injection, and aqueous humor (AqH) was collected from the eyes by anterior chamber puncture. Levels of inflammatory cytokines and chemokines in the AqH were determined with commercially available Luminex assays.
Results: Development of iris hyperemia associated with miosis and poor visibility of fundus details occurred 24 hours after LPS injection. Compared to the LPS+ group, the clinical scores were strongly suppressed in rats treated with Dexamethasone and moderately diminished in LPS+ But 0.5 mM. These clinical features were not observed in the controls (Group 1 — naive). Data from inflammatory cytokines evaluation indicates no significant differences between the LPS+ group (Group 2) and the LPS+ But groups (Groups 4 and 5). Histopathological examinations suggest that hyperemia, corneal stratification, and lesions were less common in the group of animals treated with BA in a lower concentration.
Conclusion: Topical administration of sodium butyrate as a therapeutic agent might alleviate the severity of intraocular inflammation in eyes with uveitis. The effect of sodium butyrate was slight but clinically significant in 0.5 mM dose, so other doses of topically administered sodium butyrate should be considered and evaluated in further research.
Abstract
Background: The aim of the study was to evaluate the anti-inflammatory effect of topically administered aqueous sodium butyrate solution in an endotoxin-induced uveitis rat model and compare the results with corticosteroid treatment.
Material and methods: Forty female Lewis rats were randomly divided into five groups. Uveitis was induced by a single lipopolysaccharide (LPS) injection into each footpad of each LPS+ rat. Group I (naive) received saline injected into the footpad of each rat at a dose of 0.1 mL/each footpad; Group II (LPS+) received saline solution topically. Group III (LPS+ Dex) — an aqueous dexamethasone sodium phosphate solution topically; Group IV (LPS+ But 0.5 mM) — 0.5 mM aqueous sodium butyrate solution topically, Group V (LPS+ But 1 mM) — 1.0 mM aqueous sodium butyrate solution topically. Clinical scoring of inflammation in rat eyes was evaluated before LPS injection and after 24 hours. The iris involvement, posterior synechiae presence, and insight into the eye fundus were clinicallyassessed. A histopathological examination was also performed. The rats were euthanatized 24 hours after LPS injection, and aqueous humor (AqH) was collected from the eyes by anterior chamber puncture. Levels of inflammatory cytokines and chemokines in the AqH were determined with commercially available Luminex assays.
Results: Development of iris hyperemia associated with miosis and poor visibility of fundus details occurred 24 hours after LPS injection. Compared to the LPS+ group, the clinical scores were strongly suppressed in rats treated with Dexamethasone and moderately diminished in LPS+ But 0.5 mM. These clinical features were not observed in the controls (Group 1 — naive). Data from inflammatory cytokines evaluation indicates no significant differences between the LPS+ group (Group 2) and the LPS+ But groups (Groups 4 and 5). Histopathological examinations suggest that hyperemia, corneal stratification, and lesions were less common in the group of animals treated with BA in a lower concentration.
Conclusion: Topical administration of sodium butyrate as a therapeutic agent might alleviate the severity of intraocular inflammation in eyes with uveitis. The effect of sodium butyrate was slight but clinically significant in 0.5 mM dose, so other doses of topically administered sodium butyrate should be considered and evaluated in further research.
Keywords
butyric acid; anterior uveitis; bacterial metabolites; ophthalmology; autoimmune diseases
About this articleTitle
Evaluation of butyric acid as a potential supportive treatment in anterior uveitis
Journal
Issue
Vol 7 (2022): Continuous Publishing
Article type
Original paper
Pages
117-126
Published online
2022-09-05
Page views
3903
Article views/downloads
493
DOI
Bibliographic record
Ophthalmol J 2022;7:117-126.
Keywords
butyric acid
anterior uveitis
bacterial metabolites
ophthalmology
autoimmune diseases
Authors
Karolina Krix-Jachym
Maksymilian Onyszkiewicz
Maciej Swiatkiewicz
Michal Fiedorowicz
Rafal Sapierzynski
Pawel Grieb
Marek Rekas
References (49)- Biggioggero M, Crotti C, Becciolini A, et al. The Management of Acute Anterior Uveitis Complicating Spondyloarthritis: Present and Future. Biomed Res Int. 2018; 2018: 9460187.
- Jabs DA, Nussenblatt RB, Rosenbaum JT, et al. Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol. 2005; 140(3): 509–516.
- Bloch-Michel E, Nussenblatt R. International Uveitis Study Group Recommendations for the Evaluation of Intraocular Inflammatory Disease. Am J Ophthalmol. 1987; 103(2): 234–235.
- Deschenes J, Murray PI, Rao NA, et al. International Uveitis Study Group. International Uveitis Study Group (IUSG): clinical classification of uveitis. Ocul Immunol Inflamm. 2008; 16(1): 1–2.
- Durrani OM, Tehrani NN, Marr JE, et al. Degree, duration, and causes of visual loss in uveitis. Br J Ophthalmol. 2004; 88(9): 1159–1162.
- Gritz DC, Wong IG. Incidence and prevalence of uveitis in Northern California; the Northern California Epidemiology of Uveitis Study. Ophthalmology. 2004; 111(3): 491–500; discussion 500.
- DARRELL RW, WAGENER HP, KURLAND LT. Epidemiology of uveitis. Incidence and prevalence in a small urban community. Arch Ophthalmol. 1962; 68: 502–514.
- Forrester J. Uveitis: pathogenesis. Lancet. 1991; 338(8781): 1498–1501.
- Kalogeropoulos D, Sung VCt. Pathogenesis of Uveitic Glaucoma. J Curr Glaucoma Pract. 2018; 12(3): 125–138.
- Bodaghi B, Cassoux N, Wechsler B, et al. Chronic severe uveitis: etiology and visual outcome in 927 patients from a single center. Medicine (Baltimore). 2001; 80(4): 263–270.
- Rothova A, Buitenhuis HJ, Meenken C, et al. Uveitis and systemic disease. Br J Ophthalmol. 1992; 76(3): 137–141.
- de Smet MD, Taylor SRJ, Bodaghi B, et al. Understanding uveitis: the impact of research on visual outcomes. Prog Retin Eye Res. 2011; 30(6): 452–470.
- Awan MA, Agarwal PK, Watson DG, et al. Penetration of topical and subconjunctival corticosteroids into human aqueous humour and its therapeutic significance. Br J Ophthalmol. 2009; 93(6): 708–713.
- Sharma SM, Jackson D. Uveitis and spondyloarthropathies. Best Pract Res Clin Rheumatol. 2017; 31(6): 846–862.
- Trivedi A, Katelaris C. The use of biologic agents in the management of uveitis. Intern Med J. 2019; 49(11): 1352–1363.
- Goldstein DA, Godfrey DG, Hall A, et al. Intraocular pressure in patients with uveitis treated with fluocinolone acetonide implants. Arch Ophthalmol. 2007; 125(11): 1478–1485.
- Lallemand F, Felt-Baeyens O, Besseghir K, et al. Cyclosporine A delivery to the eye: A pharmaceutical challenge. Eur J Pharm Biopharm. 2003; 56(3): 307–318.
- Jager RD, Aiello LP, Patel SC, et al. Risks of intravitreous injection: a comprehensive review. Retina. 2004; 24(5): 676–698.
- Tripathi RC, Parapuram SK, Tripathi BJ, et al. Corticosteroids and glaucoma risk. Drugs Aging. 1999; 15(6): 439–450.
- Babu K, Mahendradas P. Medical management of uveitis - current trends. Indian J Ophthalmol. 2013; 61(6): 277–283.
- Agrawal RV, Murthy S, Sangwan V, et al. Current approach in diagnosis and management of anterior uveitis. Indian J Ophthalmol. 2010; 58(1): 11–19.
- Harthan JS, Opitz DL, Fromstein SR, et al. Diagnosis and treatment of anterior uveitis: optometric management. Clin Optom (Auckl). 2016; 8: 23–35.
- Smith JR, Hart PH, Williams KA. Basic pathogenic mechanisms operating in experimental models of acute anterior uveitis. Immunol Cell Biol. 1998; 76(6): 497–512.
- Graf D, Di Cagno R, Fåk F, et al. Contribution of diet to the composition of the human gut microbiota. Microb Ecol Health Dis. 2015; 26: 26164.
- Ursell LK, Clemente JC, Rideout JR, et al. The interpersonal and intrapersonal diversity of human-associated microbiota in key body sites. J Allergy Clin Immunol. 2012; 129(5): 1204–1208.
- Bibbò S, Ianiro G, Giorgio V, et al. The role of diet on gut microbiota composition. Eur Rev Med Pharmacol Sci . 2016; 20(22): 4742–4749.
- Belkaid Y, Hand TW. Role of the microbiota in immunity and inflammation. Cell. 2014; 157(1): 121–141.
- Lazar V, Ditu LM, Pircalabioru GG, et al. Aspects of Gut Microbiota and Immune System Interactions in Infectious Diseases, Immunopathology, and Cancer. Front Immunol. 2018; 9: 1830.
- Bourassa MW, Alim I, Bultman SJ, et al. Butyrate, neuroepigenetics and the gut microbiome: Can a high fiber diet improve brain health? Neurosci Lett. 2016; 625: 56–63.
- Canani RB, Costanzo MDi, Leone L, et al. Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World J Gastroenterol. 2011; 17(12): 1519–1528.
- Chen X, Su W, Wan T, et al. Sodium butyrate regulates Th17/Treg cell balance to ameliorate uveitis via the Nrf2/HO-1 pathway. Biochem Pharmacol. 2017; 142: 111–119.
- Wang XQ, Liu HL, Wang GB, et al. Effect of artesunate on endotoxin-induced uveitis in rats. Invest Ophthalmol Vis Sci. 2011; 52(2): 916–919.
- Kim TW, Han JMo, Han YK, et al. Anti-inflammatory Effects of Extract On Endotoxin-induced Uveitis in Lewis Rats. Int J Med Sci. 2018; 15(8): 758–764.
- Wilkie DA. The Ohthalmic Examination as It Pertains to General Ocular Toxicology: Basic and Advanced Techniques and Secies-Associated Findings. In: Gilger BC. ed. Ocular Pharmacology and Toxicology. Humana Press, Totowa, NJ 2014: 143–203.
- Dusek O, Fajstova A, Klimova A, et al. Severity of Experimental Autoimmune Uveitis Is Reduced by Pretreatment with Live Probiotic Nissle 1917. Cells. 2020; 10(1).
- Kugadas A, Wright Q, Geddes-McAlister J, et al. Role of Microbiota in Strengthening Ocular Mucosal Barrier Function Through Secretory IgA. Invest Ophthalmol Vis Sci. 2017; 58(11): 4593–4600.
- Tlaskalová-Hogenová H, Stěpánková R, Kozáková H, et al. The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases. Cell Mol Immunol. 2011; 8(2): 110–120.
- Huang Y, Ding Y, Xu H, et al. Effects of sodium butyrate supplementation on inflammation, gut microbiota, and short-chain fatty acids in Helicobacter pylori-infected mice. Helicobacter. 2021; 26(2): e12785.
- Zhai S, Qin S, Li L, et al. Dietary butyrate suppresses inflammation through modulating gut microbiota in high-fat diet-fed mice. FEMS Microbiol Lett. 2019; 366(13).
- Yu C, Liu S, Chen L, et al. Effect of exercise and butyrate supplementation on microbiota composition and lipid metabolism. J Endocrinol. 2019; 243(2): 125–135.
- Fang W, Xue H, Chen Xu, et al. Supplementation with Sodium Butyrate Modulates the Composition of the Gut Microbiota and Ameliorates High-Fat Diet-Induced Obesity in Mice. J Nutr. 2019; 149(5): 747–754.
- Arpaia N, Campbell C, Fan X, et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 2013; 504(7480): 451–455.
- Singh N, Gurav A, Sivaprakasam S, et al. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity. 2014; 40(1): 128–139.
- Stilling RM, van de Wouw M, Clarke G, et al. The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis? Neurochem Int. 2016; 99: 110–132.
- Weinstein JE, Pepple KL. Cytokines in uveitis. Curr Opin Ophthalmol. 2018; 29(3): 267–274.
- Stilling RM, van de Wouw M, Clarke G, et al. The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis? Neurochem Int. 2016; 99: 110–132.
- Iraporda C, Errea A, Romanin DE, et al. Lactate and short chain fatty acids produced by microbial fermentation downregulate proinflammatory responses in intestinal epithelial cells and myeloid cells. Immunobiology. 2015; 220(10): 1161–1169.
- Hernandez H, de So, Yu Z, et al. Anti-inflammatory properties of butyrate on the ocular surface epithelium. Investig Ophthalmol Visual Sci. 2019; 60(9): 2818.
- Dinarello C. Proinflammatory Cytokines. Chest. 2000; 118(2): 503–508.