The Case for Rhodobacter Sphaeroides as a probiotic: Applications for Human Health and Ulcerative Colitis
Main Article Content
Abstract
In this short review, the mechanisms through which the probiotic administration of non-pathogenic bacterium Rhodobacter Sphaeroides could contribute to human health in general, and more specifically, the treatment of ulcerative colitis, are explored. This review is built around the concept that the mitochondrion is the key player in the pathogenesis of ulcerative colitis, and proposes ways that the probiotic could contribute to a more optimal environment for mitochondrial functioning, namely through reduction of inflammation and production of beneficial compounds like ubiquinone and bacteria-derived carotenoids. It concludes with the current state of the research involving Rhodobacter Sphaeroides as a probiotic and suggests possible future directions.
Article Details
Section
Review & Clinical Practice
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
- Authors publishing in the UOJM retain copyright of their articles, including all the drafts and the final published version in the journal.
- While UOJM does not retain any rights to the articles submitted, by agreeing to publish in UOJM, authors are granting the journal right of first publication and distribution rights of their articles.
- Authors are free to submit their works to other publications, including journals, institutional repositories or books, with an acknowledgment of its initial publication in UOJM.
- Copies of UOJM are distributed both in print and online, and all materials will be publicly available online. The journal holds no legal responsibility as to how these materials will be used by the public.
- Please ensure that all authors, co-authors and investigators have read and agree to these terms.
- Works are licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
References
1. Aizawa S-I. Chapter 21 - Rhodobacter sphaeroides — A Resourceful Little Bug. In: Aizawa S-I, editor. The Flagellar World [Internet]. Academic Press; 2014 [cited 2021 Nov 16]. p. 66–8. Available from: https://www.sciencedirect.com/science/article/pii/B9780124172340000219
2. Yen H-W, Shih T-Y. Coenzyme Q10 production by Rhodobacter sphaeroides in stirred tank and in airlift bioreactor. Bioprocess Biosyst Eng. 2009 Oct 1;32(6):711–6.
3. Urakami T, Yoshida T. Production of ubiquinone and bacteriochlorophyll a by Rhodobacter sphaeroides and Rhodobacter sulfidophilus. Journal of Fermentation and Bioengineering. 1993 Jan 1;76(3):191–4.
4. Yeliseev AA, Eraso JM, Kaplan S. Differential carotenoid composition of the B875 and B800-850 photosynthetic antenna complexes in Rhodobacter sphaeroides 2.4.1: involvement of spheroidene and spheroidenone in adaptation to changes in light intensity and oxygen availability. J Bacteriol. 1996 Oct;178(20):5877–83.
5. Kien NB, Kong I-S, Lee M-G, Kim JK. Coenzyme Q10 production in a 150-l reactor by a mutant strain of Rhodobacter sphaeroides. Journal of Industrial Microbiology and Biotechnology. 2010 May 1;37(5):521–9.
6. Zhang L, Liu L, Wang K-F, Xu L, Zhou L, Wang W, et al. Phosphate limitation increases coenzyme Q10 production in industrial Rhodobacter sphaeroides HY01. Synthetic and Systems Biotechnology. 2019 Dec 1;4(4):212–9.
7. Bai H-J, Zhang Z-M, Yang G-E, Li B-Z. Bioremediation of cadmium by growing Rhodobacter sphaeroides: Kinetic characteristic and mechanism studies. Bioresource Technology. 2008 Nov 1;99(16):7716–22.
8. Merugu R. Bioremediation of waste waters by the anoxygenic photosynthetic bacterium Rhodobacter sphaeroides SMR 009. International journal of research in Environmental Science and Technology. 2014 Oct 15;
9. Hai NV. Research findings from the use of probiotics in tilapia aquaculture: A review. Fish & Shellfish Immunology. 2015 Aug 1;45(2):592–7.
10. Chumpol S, Kantachote D, Rattanachuay P, Vuddhakul V, Nitoda T, Kanzaki H. In vitro and in vivo selection of probiotic purple nonsulphur bacteria with an ability to inhibit shrimp pathogens: acute hepatopancreatic necrosis disease-causing Vibrio parahaemolyticus and other vibrios. Aquaculture Research. 2017;48(6):3182–97.
11. Chumpol S, Kantachote D, Nitoda T, Kanzaki H. The roles of probiotic purple nonsulfur bacteria to control water quality and prevent acute hepatopancreatic necrosis disease (AHPND) for enhancement growth with higher survival in white shrimp (Litopenaeus vannamei) during cultivation. Aquaculture. 2017 Apr 20;473:327–36.
12. Yang C, Luan N, An J, Zhang M, Li Z, Li Q, et al. The Effects of Rhodobacter sphaeroides on the Composition of Gut Microbiota and Short-chain Fatty Acids in Mice. JFNR. 2020 Jul 15;8(6):288–96.
13. An J, Yang C, Li Z, Finn PW, Perkins DL, Sun J, et al. In vitro antioxidant activities of Rhodobacter sphaeroides and protective effect on Caco-2 cell line model. Appl Microbiol Biotechnol. 2019 Jan 1;103(2):917–27.
14. Wang C-C, Ding S, Chiu K-H, Liu W-S, Lin T-J, Wen Z-H. Extract from a mutant Rhodobacter sphaeroides as an enriched carotenoid source. Food Nutr Res. 2016;60:29580.
15. Liu W-S, Chen M-C, Chiu K-H, Wen Z-H, Lee C-H. Amelioration of Dextran Sodium Sulfate-Induced Colitis in Mice by Rhodobacter sphaeroides Extract. Molecules. 2012 Nov 16;17(11):13622–30.
16. Chang W-W, Liu J-J, Liu C-F, Liu W-S, Lim Y-P, Cheng Y-J, et al. An Extract of Rhodobacter sphaeroides Reduces Cisplatin-Induced Nephrotoxicity in Mice. Toxins (Basel). 2013 Nov 29;5(12):2353–65.
17. Chassaing B, Darfeuille-Michaud A. The commensal microbiota and enteropathogens in the pathogenesis of inflammatory bowel diseases. Gastroenterology. 2011 May;140(6):1720–8.
18. Machiels K, Joossens M, Sabino J, De Preter V, Arijs I, Eeckhaut V, et al. A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut. 2014 Aug;63(8):1275–83.
19. Sasaki M, Klapproth J-MA. The Role of Bacteria in the Pathogenesis of Ulcerative Colitis. Journal of Signal Transduction [Internet]. 2012 [cited 2021 Dec 6];2012. Available from: https://www.ncbi.nlm.nih.gov/sites/ppmc/articles/PMC3348635/
20. Shen J, Zuo Z-X, Mao A-P. Effect of probiotics on inducing remission and maintaining therapy in ulcerative colitis, Crohn’s disease, and pouchitis: meta-analysis of randomized controlled trials. Inflamm Bowel Dis. 2014 Jan;20(1):21–35.
21. Shen Z-H, Zhu C-X, Quan Y-S, Yang Z-Y, Wu S, Luo W-W, et al. Relationship between intestinal microbiota and ulcerative colitis: Mechanisms and clinical application of probiotics and fecal microbiota transplantation. World J Gastroenterol. 2018 Jan 7;24(1):5–14.
22. Anhê FF, Barra NG, Cavallari JF, Henriksbo BD, Schertzer JD. Metabolic endotoxemia is dictated by the type of lipopolysaccharide. Cell Reports. 2021 Sep;36(11):109691.
23. Coats SR, Pham T-TT, Bainbridge BW, Reife RA, Darveau RP. MD-2 Mediates the Ability of Tetra-Acylated and Penta-Acylated Lipopolysaccharides to Antagonize Escherichia coli Lipopolysaccharide at the TLR4 Signaling Complex. The Journal of Immunology. 2005 Oct 1;175(7):4490–8.
24. Gardiner KR, Halliday MI, Barclay GR, Milne L, Brown D, Stephens S, et al. Significance of systemic endotoxaemia in inflammatory bowel disease. Gut. 1995 Jun;36(6):897–901.
25. Aoki K. A study of endotoxemia in ulcerative colitis and Crohn’s disease. I. Clinical study. Acta Med Okayama. 1978 Jun;32(2):147–58.
26. Caradonna L, Amati L, Magrone T, Pellegrino NM, Jirillo E, Caccavo D. Enteric bacteria, lipopolysaccharides and related cytokines in inflammatory bowel disease: biological and clinical significance. J Endotoxin Res. 2000;6(3):205–14.
27. McDonnell M, Liang Y, Noronha A, Coukos J, Kasper DL, Farraye FA, et al. Systemic Toll-like receptor ligands modify B-cell responses in human inflammatory bowel disease. Inflamm Bowel Dis. 2011 Jan;17(1):298–307.
28. Tam JSY, Coller JK, Hughes PA, Prestidge CA, Bowen JM. Toll-like receptor 4 (TLR4) antagonists as potential therapeutics for intestinal inflammation. Indian J Gastroenterol. 2021 Feb;40(1):5–21.
29. Kameyama J, Narui H, Inui M, Sato T. Energy level in large intestinal mucosa in patients with ulcerative colitis. Tohoku J Exp Med. 1984 Jun;143(2):253–4.
30. Roediger WE. The colonic epithelium in ulcerative colitis: an energy-deficiency disease? Lancet. 1980 Oct 4;2(8197):712–5.
31. Chapman MA, Grahn MF, Boyle MA, Hutton M, Rogers J, Williams NS. Butyrate oxidation is impaired in the colonic mucosa of sufferers of quiescent ulcerative colitis. Gut. 1994 Jan;35(1):73–6.
32. Thibault R, Blachier F, Darcy-Vrillon B, de Coppet P, Bourreille A, Segain J-P. Butyrate utilization by the colonic mucosa in inflammatory bowel diseases: a transport deficiency. Inflamm Bowel Dis. 2010 Apr;16(4):684–95.
33. SÜNDERHAUF A, Hicken M, Skibbe K, Schlichting H, Hirose M, Perner S, et al. P007 GC1qR driven oxidative phosphorylation is essential for intestinal goblet cell differentiation. Journal of Crohn’s and Colitis. 2020 Jan 15;14(Supplement_1):S133.
34. Sünderhauf A, Hicken M, Schlichting H, Skibbe K, Ragab M, Raschdorf A, et al. Loss of Mucosal p32/gC1qR/HABP1 Triggers Energy Deficiency and Impairs Goblet Cell Differentiation in Ulcerative Colitis. Cell Mol Gastroenterol Hepatol. 2021 Jan 27;12(1):229–50.
35. Kim YS, Ho SB. Intestinal Goblet Cells and Mucins in Health and Disease: Recent Insights and Progress. Curr Gastroenterol Rep. 2010;12(5):319–30.
36. Haberman Y, Karns R, Dexheimer PJ, Schirmer M, Somekh J, Jurickova I, et al. Ulcerative colitis mucosal transcriptomes reveal mitochondriopathy and personalized mechanisms underlying disease severity and treatment response. Nat Commun. 2019 Jan 3;10(1):38.
37. Santhanam S, Rajamanickam S, Motamarry A, Ramakrishna BS, Amirtharaj JG, Ramachandran A, et al. Mitochondrial electron transport chain complex dysfunction in the colonic mucosa in ulcerative colitis. Inflamm Bowel Dis. 2012 Nov;18(11):2158–68.
38. Sifroni KG, Damiani CR, Stoffel C, Cardoso MR, Ferreira GK, Jeremias IC, et al. Mitochondrial respiratory chain in the colonic mucosal of patients with ulcerative colitis. Mol Cell Biochem. 2010 Sep;342(1–2):111–5.
39. Schniers A, Goll R, Pasing Y, Sørbye SW, Florholmen J, Hansen T. Ulcerative colitis: functional analysis of the in-depth proteome. Clinical Proteomics. 2019 Jan 29;16(1):4.
40. Gersemann M, Becker S, Kübler I, Koslowski M, Wang G, Herrlinger KR, et al. Differences in goblet cell differentiation between Crohn’s disease and ulcerative colitis. Differentiation. 2009 Jan;77(1):84–94.
41. Post S van der, Jabbar KS, Birchenough G, Arike L, Akhtar N, Sjovall H, et al. Structural weakening of the colonic mucus barrier is an early event in ulcerative colitis pathogenesis. Gut. 2019 Dec 1;68(12):2142–51.
42. Wu B, Li J, Ni H, Zhuang X, Qi Z, Chen Q, et al. TLR4 Activation Promotes the Progression of Experimental Autoimmune Myocarditis to Dilated Cardiomyopathy by Inducing Mitochondrial Dynamic Imbalance. Oxidative Medicine and Cellular Longevity. 2018 Jun 26;2018:e3181278.
43. Kapetanovic R, Afroz SF, Ramnath D, Lawrence GM, Okada T, Curson JE, et al. Lipopolysaccharide promotes Drp1-dependent mitochondrial fission and associated inflammatory responses in macrophages. Immunol Cell Biol. 2020 Aug;98(7):528–39.
44. Zhong Z, Umemura A, Sanchez-Lopez E, Liang S, Shalapour S, Wong J, et al. NF-κB Restricts Inflammasome Activation via Elimination of Damaged Mitochondria. Cell. 2016 Feb 25;164(5):896–910.
45. Neal MD, Sodhi CP, Jia H, Dyer M, Egan CE, Yazji I, et al. Toll-like receptor 4 is expressed on intestinal stem cells and regulates their proliferation and apoptosis via the p53 up-regulated modulator of apoptosis. J Biol Chem. 2012 Oct 26;287(44):37296–308.
46. El Morsy EM, Kamel R, Ahmed MAE. Attenuating effects of coenzyme Q10 and amlodipine in ulcerative colitis model in rats. Immunopharmacology and Immunotoxicology. 2015 May 4;37(3):244–51.
47. Ewees MG, Messiha BAS, Abo-Saif AA, Abd El-Latif HAE-T. Is Coenzyme Q10 Effective in Protection against Ulcerative Colitis? An Experimental Study in Rats. Biol Pharm Bull. 2016;39(7):1159–66.
48. Khodir AE, Atef H, Said E, ElKashef HA, Salem HA. Implication of Nrf2/HO-1 pathway in the coloprotective effect of coenzyme Q10 against experimentally induced ulcerative colitis. Inflammopharmacology. 2017 Feb;25(1):119–35.
49. Lee S-Y, Lee SH, Yang E-J, Kim J-K, Kim E-K, Jung K, et al. Coenzyme Q10 Inhibits Th17 and STAT3 Signaling Pathways to Ameliorate Colitis in Mice. Journal of Medicinal Food. 2017 Sep 1;20(9):821–9.
50. Korkina L, Suprun M, Petrova A, Mikhal’Chik E, Luci A, Luca CD. The protective and healing effects of a natural antioxidant formulation based on ubiquinol and Aloe vera against dextran sulfate-induced ulcerative colitis in rats. BioFactors. 2003;18(1–4):255–64.
51. Liu, Russell, Smith, Bronson, Milbury, Furukawa, et al. The Effect of Dietary Glutathione and Coenzyme Q10 on the Prevention and Treatment of Inflammatory Bowel Disease in Mice. International Journal for Vitamin and Nutrition Research. 2004 Jan 1;74(1):74–85.
52. Kagan T, Davis C, Lin L, Zakeri Z. Coenzyme Q10 Can in Some Circumstances Block Apoptosis, and This Effect Is Mediated through Mitochondria. Annals of the New York Academy of Sciences. 1999;887(1):31–47.
53. Papucci L, Schiavone N, Witort E, Donnini M, Lapucci A, Tempestini A, et al. Coenzyme Q10 Prevents Apoptosis by Inhibiting Mitochondrial Depolarization Independently of Its Free Radical Scavenging Property *. Journal of Biological Chemistry. 2003 Jul 25;278(30):28220–8.
54. Farsi F, Ebrahimi-Daryani N, Barati M, Janani L, Karimi MY, Akbari A, et al. Effects of coenzyme Q10 on health-related quality of life, clinical disease activity and blood pressure in patients with mild to moderate ulcerative colitis: a randomized clinical trial. Med J Islam Repub Iran. 2021 Jan 6;35:3.
55. Bae G-S, Choi A, Yeo JM, Kim JN, Song J, Kim EJ, et al. Supplementing Rhodobacter sphaeroides in the diet of lactating Holstein cows may naturally produce coenzyme Q10-enriched milk. Asian-Australas J Anim Sci. 2018 Jan;31(1):40–6.
56. Wang Y, Chen S, Liu J, Lv P, Cai D, Zhao G. Efficient production of coenzyme Q 10 from acid hydrolysate of sweet sorghum juice by Rhodobacter sphaeroides. RSC Advances. 2019;9(39):22336–42.
57. Swidsinski A, Ladhoff A, Pernthaler A, Swidsinski S, Loening-Baucke V, Ortner M, et al. Mucosal flora in inflammatory bowel disease. Gastroenterology. 2002 Jan;122(1):44–54.
58. Bär F, Bochmann W, Widok A, von Medem K, Pagel R, Hirose M, et al. Mitochondrial gene polymorphisms that protect mice from colitis. Gastroenterology. 2013 Nov;145(5):1055-1063.e3.
59. Yu X, Wieczorek S, Franke A, Yin H, Pierer M, Sina C, et al. Association of UCP2 −866 G/A polymorphism with chronic inflammatory diseases. Genes Immun. 2009 Sep;10(6):601–5.
60. Dankowski T, Schröder T, Möller S, Yu X, Ellinghaus D, Bär F, et al. Male-specific association between MT-ND4 11719 A/G polymorphism and ulcerative colitis: a mitochondria-wide genetic association study. BMC Gastroenterol. 2016 Oct 3;16(1):118.
61. McGovern DPB, Gardet A, Törkvist L, Goyette P, Essers J, Taylor KD, et al. Genome-wide association identifies multiple ulcerative colitis susceptibility loci. Nat Genet. 2010 Apr;42(4):332–7.
2. Yen H-W, Shih T-Y. Coenzyme Q10 production by Rhodobacter sphaeroides in stirred tank and in airlift bioreactor. Bioprocess Biosyst Eng. 2009 Oct 1;32(6):711–6.
3. Urakami T, Yoshida T. Production of ubiquinone and bacteriochlorophyll a by Rhodobacter sphaeroides and Rhodobacter sulfidophilus. Journal of Fermentation and Bioengineering. 1993 Jan 1;76(3):191–4.
4. Yeliseev AA, Eraso JM, Kaplan S. Differential carotenoid composition of the B875 and B800-850 photosynthetic antenna complexes in Rhodobacter sphaeroides 2.4.1: involvement of spheroidene and spheroidenone in adaptation to changes in light intensity and oxygen availability. J Bacteriol. 1996 Oct;178(20):5877–83.
5. Kien NB, Kong I-S, Lee M-G, Kim JK. Coenzyme Q10 production in a 150-l reactor by a mutant strain of Rhodobacter sphaeroides. Journal of Industrial Microbiology and Biotechnology. 2010 May 1;37(5):521–9.
6. Zhang L, Liu L, Wang K-F, Xu L, Zhou L, Wang W, et al. Phosphate limitation increases coenzyme Q10 production in industrial Rhodobacter sphaeroides HY01. Synthetic and Systems Biotechnology. 2019 Dec 1;4(4):212–9.
7. Bai H-J, Zhang Z-M, Yang G-E, Li B-Z. Bioremediation of cadmium by growing Rhodobacter sphaeroides: Kinetic characteristic and mechanism studies. Bioresource Technology. 2008 Nov 1;99(16):7716–22.
8. Merugu R. Bioremediation of waste waters by the anoxygenic photosynthetic bacterium Rhodobacter sphaeroides SMR 009. International journal of research in Environmental Science and Technology. 2014 Oct 15;
9. Hai NV. Research findings from the use of probiotics in tilapia aquaculture: A review. Fish & Shellfish Immunology. 2015 Aug 1;45(2):592–7.
10. Chumpol S, Kantachote D, Rattanachuay P, Vuddhakul V, Nitoda T, Kanzaki H. In vitro and in vivo selection of probiotic purple nonsulphur bacteria with an ability to inhibit shrimp pathogens: acute hepatopancreatic necrosis disease-causing Vibrio parahaemolyticus and other vibrios. Aquaculture Research. 2017;48(6):3182–97.
11. Chumpol S, Kantachote D, Nitoda T, Kanzaki H. The roles of probiotic purple nonsulfur bacteria to control water quality and prevent acute hepatopancreatic necrosis disease (AHPND) for enhancement growth with higher survival in white shrimp (Litopenaeus vannamei) during cultivation. Aquaculture. 2017 Apr 20;473:327–36.
12. Yang C, Luan N, An J, Zhang M, Li Z, Li Q, et al. The Effects of Rhodobacter sphaeroides on the Composition of Gut Microbiota and Short-chain Fatty Acids in Mice. JFNR. 2020 Jul 15;8(6):288–96.
13. An J, Yang C, Li Z, Finn PW, Perkins DL, Sun J, et al. In vitro antioxidant activities of Rhodobacter sphaeroides and protective effect on Caco-2 cell line model. Appl Microbiol Biotechnol. 2019 Jan 1;103(2):917–27.
14. Wang C-C, Ding S, Chiu K-H, Liu W-S, Lin T-J, Wen Z-H. Extract from a mutant Rhodobacter sphaeroides as an enriched carotenoid source. Food Nutr Res. 2016;60:29580.
15. Liu W-S, Chen M-C, Chiu K-H, Wen Z-H, Lee C-H. Amelioration of Dextran Sodium Sulfate-Induced Colitis in Mice by Rhodobacter sphaeroides Extract. Molecules. 2012 Nov 16;17(11):13622–30.
16. Chang W-W, Liu J-J, Liu C-F, Liu W-S, Lim Y-P, Cheng Y-J, et al. An Extract of Rhodobacter sphaeroides Reduces Cisplatin-Induced Nephrotoxicity in Mice. Toxins (Basel). 2013 Nov 29;5(12):2353–65.
17. Chassaing B, Darfeuille-Michaud A. The commensal microbiota and enteropathogens in the pathogenesis of inflammatory bowel diseases. Gastroenterology. 2011 May;140(6):1720–8.
18. Machiels K, Joossens M, Sabino J, De Preter V, Arijs I, Eeckhaut V, et al. A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut. 2014 Aug;63(8):1275–83.
19. Sasaki M, Klapproth J-MA. The Role of Bacteria in the Pathogenesis of Ulcerative Colitis. Journal of Signal Transduction [Internet]. 2012 [cited 2021 Dec 6];2012. Available from: https://www.ncbi.nlm.nih.gov/sites/ppmc/articles/PMC3348635/
20. Shen J, Zuo Z-X, Mao A-P. Effect of probiotics on inducing remission and maintaining therapy in ulcerative colitis, Crohn’s disease, and pouchitis: meta-analysis of randomized controlled trials. Inflamm Bowel Dis. 2014 Jan;20(1):21–35.
21. Shen Z-H, Zhu C-X, Quan Y-S, Yang Z-Y, Wu S, Luo W-W, et al. Relationship between intestinal microbiota and ulcerative colitis: Mechanisms and clinical application of probiotics and fecal microbiota transplantation. World J Gastroenterol. 2018 Jan 7;24(1):5–14.
22. Anhê FF, Barra NG, Cavallari JF, Henriksbo BD, Schertzer JD. Metabolic endotoxemia is dictated by the type of lipopolysaccharide. Cell Reports. 2021 Sep;36(11):109691.
23. Coats SR, Pham T-TT, Bainbridge BW, Reife RA, Darveau RP. MD-2 Mediates the Ability of Tetra-Acylated and Penta-Acylated Lipopolysaccharides to Antagonize Escherichia coli Lipopolysaccharide at the TLR4 Signaling Complex. The Journal of Immunology. 2005 Oct 1;175(7):4490–8.
24. Gardiner KR, Halliday MI, Barclay GR, Milne L, Brown D, Stephens S, et al. Significance of systemic endotoxaemia in inflammatory bowel disease. Gut. 1995 Jun;36(6):897–901.
25. Aoki K. A study of endotoxemia in ulcerative colitis and Crohn’s disease. I. Clinical study. Acta Med Okayama. 1978 Jun;32(2):147–58.
26. Caradonna L, Amati L, Magrone T, Pellegrino NM, Jirillo E, Caccavo D. Enteric bacteria, lipopolysaccharides and related cytokines in inflammatory bowel disease: biological and clinical significance. J Endotoxin Res. 2000;6(3):205–14.
27. McDonnell M, Liang Y, Noronha A, Coukos J, Kasper DL, Farraye FA, et al. Systemic Toll-like receptor ligands modify B-cell responses in human inflammatory bowel disease. Inflamm Bowel Dis. 2011 Jan;17(1):298–307.
28. Tam JSY, Coller JK, Hughes PA, Prestidge CA, Bowen JM. Toll-like receptor 4 (TLR4) antagonists as potential therapeutics for intestinal inflammation. Indian J Gastroenterol. 2021 Feb;40(1):5–21.
29. Kameyama J, Narui H, Inui M, Sato T. Energy level in large intestinal mucosa in patients with ulcerative colitis. Tohoku J Exp Med. 1984 Jun;143(2):253–4.
30. Roediger WE. The colonic epithelium in ulcerative colitis: an energy-deficiency disease? Lancet. 1980 Oct 4;2(8197):712–5.
31. Chapman MA, Grahn MF, Boyle MA, Hutton M, Rogers J, Williams NS. Butyrate oxidation is impaired in the colonic mucosa of sufferers of quiescent ulcerative colitis. Gut. 1994 Jan;35(1):73–6.
32. Thibault R, Blachier F, Darcy-Vrillon B, de Coppet P, Bourreille A, Segain J-P. Butyrate utilization by the colonic mucosa in inflammatory bowel diseases: a transport deficiency. Inflamm Bowel Dis. 2010 Apr;16(4):684–95.
33. SÜNDERHAUF A, Hicken M, Skibbe K, Schlichting H, Hirose M, Perner S, et al. P007 GC1qR driven oxidative phosphorylation is essential for intestinal goblet cell differentiation. Journal of Crohn’s and Colitis. 2020 Jan 15;14(Supplement_1):S133.
34. Sünderhauf A, Hicken M, Schlichting H, Skibbe K, Ragab M, Raschdorf A, et al. Loss of Mucosal p32/gC1qR/HABP1 Triggers Energy Deficiency and Impairs Goblet Cell Differentiation in Ulcerative Colitis. Cell Mol Gastroenterol Hepatol. 2021 Jan 27;12(1):229–50.
35. Kim YS, Ho SB. Intestinal Goblet Cells and Mucins in Health and Disease: Recent Insights and Progress. Curr Gastroenterol Rep. 2010;12(5):319–30.
36. Haberman Y, Karns R, Dexheimer PJ, Schirmer M, Somekh J, Jurickova I, et al. Ulcerative colitis mucosal transcriptomes reveal mitochondriopathy and personalized mechanisms underlying disease severity and treatment response. Nat Commun. 2019 Jan 3;10(1):38.
37. Santhanam S, Rajamanickam S, Motamarry A, Ramakrishna BS, Amirtharaj JG, Ramachandran A, et al. Mitochondrial electron transport chain complex dysfunction in the colonic mucosa in ulcerative colitis. Inflamm Bowel Dis. 2012 Nov;18(11):2158–68.
38. Sifroni KG, Damiani CR, Stoffel C, Cardoso MR, Ferreira GK, Jeremias IC, et al. Mitochondrial respiratory chain in the colonic mucosal of patients with ulcerative colitis. Mol Cell Biochem. 2010 Sep;342(1–2):111–5.
39. Schniers A, Goll R, Pasing Y, Sørbye SW, Florholmen J, Hansen T. Ulcerative colitis: functional analysis of the in-depth proteome. Clinical Proteomics. 2019 Jan 29;16(1):4.
40. Gersemann M, Becker S, Kübler I, Koslowski M, Wang G, Herrlinger KR, et al. Differences in goblet cell differentiation between Crohn’s disease and ulcerative colitis. Differentiation. 2009 Jan;77(1):84–94.
41. Post S van der, Jabbar KS, Birchenough G, Arike L, Akhtar N, Sjovall H, et al. Structural weakening of the colonic mucus barrier is an early event in ulcerative colitis pathogenesis. Gut. 2019 Dec 1;68(12):2142–51.
42. Wu B, Li J, Ni H, Zhuang X, Qi Z, Chen Q, et al. TLR4 Activation Promotes the Progression of Experimental Autoimmune Myocarditis to Dilated Cardiomyopathy by Inducing Mitochondrial Dynamic Imbalance. Oxidative Medicine and Cellular Longevity. 2018 Jun 26;2018:e3181278.
43. Kapetanovic R, Afroz SF, Ramnath D, Lawrence GM, Okada T, Curson JE, et al. Lipopolysaccharide promotes Drp1-dependent mitochondrial fission and associated inflammatory responses in macrophages. Immunol Cell Biol. 2020 Aug;98(7):528–39.
44. Zhong Z, Umemura A, Sanchez-Lopez E, Liang S, Shalapour S, Wong J, et al. NF-κB Restricts Inflammasome Activation via Elimination of Damaged Mitochondria. Cell. 2016 Feb 25;164(5):896–910.
45. Neal MD, Sodhi CP, Jia H, Dyer M, Egan CE, Yazji I, et al. Toll-like receptor 4 is expressed on intestinal stem cells and regulates their proliferation and apoptosis via the p53 up-regulated modulator of apoptosis. J Biol Chem. 2012 Oct 26;287(44):37296–308.
46. El Morsy EM, Kamel R, Ahmed MAE. Attenuating effects of coenzyme Q10 and amlodipine in ulcerative colitis model in rats. Immunopharmacology and Immunotoxicology. 2015 May 4;37(3):244–51.
47. Ewees MG, Messiha BAS, Abo-Saif AA, Abd El-Latif HAE-T. Is Coenzyme Q10 Effective in Protection against Ulcerative Colitis? An Experimental Study in Rats. Biol Pharm Bull. 2016;39(7):1159–66.
48. Khodir AE, Atef H, Said E, ElKashef HA, Salem HA. Implication of Nrf2/HO-1 pathway in the coloprotective effect of coenzyme Q10 against experimentally induced ulcerative colitis. Inflammopharmacology. 2017 Feb;25(1):119–35.
49. Lee S-Y, Lee SH, Yang E-J, Kim J-K, Kim E-K, Jung K, et al. Coenzyme Q10 Inhibits Th17 and STAT3 Signaling Pathways to Ameliorate Colitis in Mice. Journal of Medicinal Food. 2017 Sep 1;20(9):821–9.
50. Korkina L, Suprun M, Petrova A, Mikhal’Chik E, Luci A, Luca CD. The protective and healing effects of a natural antioxidant formulation based on ubiquinol and Aloe vera against dextran sulfate-induced ulcerative colitis in rats. BioFactors. 2003;18(1–4):255–64.
51. Liu, Russell, Smith, Bronson, Milbury, Furukawa, et al. The Effect of Dietary Glutathione and Coenzyme Q10 on the Prevention and Treatment of Inflammatory Bowel Disease in Mice. International Journal for Vitamin and Nutrition Research. 2004 Jan 1;74(1):74–85.
52. Kagan T, Davis C, Lin L, Zakeri Z. Coenzyme Q10 Can in Some Circumstances Block Apoptosis, and This Effect Is Mediated through Mitochondria. Annals of the New York Academy of Sciences. 1999;887(1):31–47.
53. Papucci L, Schiavone N, Witort E, Donnini M, Lapucci A, Tempestini A, et al. Coenzyme Q10 Prevents Apoptosis by Inhibiting Mitochondrial Depolarization Independently of Its Free Radical Scavenging Property *. Journal of Biological Chemistry. 2003 Jul 25;278(30):28220–8.
54. Farsi F, Ebrahimi-Daryani N, Barati M, Janani L, Karimi MY, Akbari A, et al. Effects of coenzyme Q10 on health-related quality of life, clinical disease activity and blood pressure in patients with mild to moderate ulcerative colitis: a randomized clinical trial. Med J Islam Repub Iran. 2021 Jan 6;35:3.
55. Bae G-S, Choi A, Yeo JM, Kim JN, Song J, Kim EJ, et al. Supplementing Rhodobacter sphaeroides in the diet of lactating Holstein cows may naturally produce coenzyme Q10-enriched milk. Asian-Australas J Anim Sci. 2018 Jan;31(1):40–6.
56. Wang Y, Chen S, Liu J, Lv P, Cai D, Zhao G. Efficient production of coenzyme Q 10 from acid hydrolysate of sweet sorghum juice by Rhodobacter sphaeroides. RSC Advances. 2019;9(39):22336–42.
57. Swidsinski A, Ladhoff A, Pernthaler A, Swidsinski S, Loening-Baucke V, Ortner M, et al. Mucosal flora in inflammatory bowel disease. Gastroenterology. 2002 Jan;122(1):44–54.
58. Bär F, Bochmann W, Widok A, von Medem K, Pagel R, Hirose M, et al. Mitochondrial gene polymorphisms that protect mice from colitis. Gastroenterology. 2013 Nov;145(5):1055-1063.e3.
59. Yu X, Wieczorek S, Franke A, Yin H, Pierer M, Sina C, et al. Association of UCP2 −866 G/A polymorphism with chronic inflammatory diseases. Genes Immun. 2009 Sep;10(6):601–5.
60. Dankowski T, Schröder T, Möller S, Yu X, Ellinghaus D, Bär F, et al. Male-specific association between MT-ND4 11719 A/G polymorphism and ulcerative colitis: a mitochondria-wide genetic association study. BMC Gastroenterol. 2016 Oct 3;16(1):118.
61. McGovern DPB, Gardet A, Törkvist L, Goyette P, Essers J, Taylor KD, et al. Genome-wide association identifies multiple ulcerative colitis susceptibility loci. Nat Genet. 2010 Apr;42(4):332–7.