Vitamin C improves gut Bifidobacteria in humans

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References

• 1. Pauling L. Vitamin C and common cold. JAMA 216(2), 332–332 (1971).
  Medline CASGoogle Scholar
• 2. Pauling L. Respect for vitamin C. Science 254(5039), 1712 (1991). • Fundamental studies showing the roles of vitamin C.
  Google Scholar
• 3. Hemilä H, Chalker E. Vitamin C for preventing and treating the common cold. Cochrane Database Systematic Rev. (2013). https://www.cochrane.org/CD000980/ARI_vitamin-c-for-preventing-and-treating-the-common-cold
  Google Scholar
• 4. Ran L, Zhao W, Wang J et al. Extra dose of vitamin C based on a daily supplementation shortens the common cold: a meta-analysis of 9 randomized controlled trials. Biomed Res Int. doi:10.1155/2018/1837634 (2018) (Epub ahead of print).
  Google Scholar
• 5. Anderson TWRDB, Beaton GH. Vitamin C and the common cold: a double-blind trial. Can Med Assoc J. l107(6), 503–508 (1972).
  Google Scholar
• 6. Coulehan JL, Eberhard S, Kapner L, Taylor F, Rogers K, Garry P. Vitamin C and acute illness in Navajo school children. N. Engl. J. Med. 295(18), 973–977 (1976).
  Medline CASGoogle Scholar
• 7. Sasazuki S, Sasaki S, Tsubono Y, Okubo S, Hayashi M, Tsugane S. Effect of vitamin C on common cold: randomized controlled trial. Eur. J. Clin. Nutr. 60(1), 9–17 (2006).
  Medline CASGoogle Scholar
• 8. Anderson TW, Suranyi G, Beaton GH. The effect on winter illness of large doses of vitamin C. Can. Med. Assoc. J. 111, 31–36 (1974).
  Medline CASGoogle Scholar
• 9. Bancalari A, Seguel, Neira C, Ruiz FI, Calvo C. [Prophylactic value of vitamin C in acute respiratory tract infections in schoolchildren] Rev. Med. Chil. 112(9), 871–876 (1984).
  Medline CASGoogle Scholar
• 10. Briggs M. Vitamin C and infectious diesease: a review of the literature and the results of a randomized, double-blind, prospective study over 8 years. In recent Vitamin Research 39–82 (1984). https://www.taylorfrancis.com/books/edit/10.1201/9780203710562/recent-vitamin-research-1984-briggs-michael?refId=052c615e-cb54-4e84-a40e-347422f4d9b9&context=ubx
  Google Scholar
• 11. Carr AB, Einstein R, Lai LYC, Martin NG, Starmer GA. Vitamin C and the common cold: a second MZ co-twin control study. Acta Genet. Med. Gemellol. 30(4), 249–255 (1981).
  Medline CASGoogle Scholar
• 12. Charleston SS, Clegg KM. Ascorbic acid and the common cold. Lancet 1(7765), 1401–1402 (1972).
  Medline CASGoogle Scholar
• 13. Clegg KM, Macdonald JM. L-Ascorbic acid and D-isoascorbic acid in a common cold survey. Am. J. Clin. Nutr. 28(9), 973–976 (1975).
  Medline CASGoogle Scholar
• 14. Elliott B. Ascorbic acid: efficacy in the prevention of symptoms of respiratory infection on a Polaris submarine. Int. Res. Commun. Syst./Med. Sci. 1(3), 12 (1973).
  Google Scholar
• 15. Elwood PC, Lee HP, St Leger AS, Baird M, Howard AN. A randomized controlled trial of vitamin C in the prevention and amelioration of the common cold. Br. J. Prev. Soc. Med. 30(3), 193–196 (1976).
  Medline CASGoogle Scholar
• 16. Karlowski TR, Chalmers TC, Frenkel LD, Kapikian AZ, Lewis TL, Lynch JM. Ascorbic acid for the common cold: a prophylactic and therapeutic trial. JAMA 231(10), 1038–1042 (1975).
  Medline CASGoogle Scholar
• 17. Ludvigsson J, Olof Hansson L, Tibbling G. Vitamin C as a preventive medicine against common colds in children. Scand. J. Infect. Dis. 9(2), 91–98 (1977).
  Medline CASGoogle Scholar
• 18. K.A.Mink, E.C.Dick, Lance C Jennings. Amelioration of rhinovirus colds by vitamin C (ascorbic acid) supplementation. Medical Virology VII 241, 909–911 (1979).
  Google Scholar
• 19. Pitt HA, Costrini AM. Vitamin C prophylaxis in marine recruits. JAMA 241(9), 908–911 (1979).
  Medline CASGoogle Scholar
• 20. Schwartz AR, Togo Y, Hornick RB, Tominaga S, Gleckman RA. Evaluation of the efficacy of ascorbic acid in prophylaxis of induced rhinovirus 44 infection in man. J. Infect. Dis. 128(4), 500–505 (1973).
  Medline CASGoogle Scholar
• 21. Wexler HM. Bacteroides: the good, the bad, and the nitty-gritty. Clin. Microbiol. Rev. 20(4), 593–621 (2007).
  Medline CASGoogle Scholar
• 22. Spiers PS. On the prevention of the common cold: no help from vitamin C. Epidemiology 13(1), 4–5 (2002).
  MedlineGoogle Scholar
• 23. Travica N, Ried K, Sali A, Scholey A, Hudson I, Pipingas A. Vitamin C status and cognitive function: a systematic review. Nutrients 9(9), 960 (2017).
  MedlineGoogle Scholar
• 24. Mayland CR, Bennett MI, Allan K. Vitamin C deficiency in cancer patients. Palliat. Med. 19(1), 17–20 (2005).
  MedlineGoogle Scholar
• 25. Tomasa-Irriguible TM, Bielsa-Berrocal L. COVID-19: up to 82% critically ill patients had low vitamin C values. Nutr. J. 20(1), 66 (2021).
  Medline CASGoogle Scholar
• 26. Rowe S, Carr AC. Global vitamin C status and prevalence of deficiency: a cause for concern? Nutrients 12(7), 2008 (2020).
  Medline CASGoogle Scholar
• 27. Schleicher RL, Carroll MD, Ford ES, Lacher DA. Serum vitamin C and the prevalence of vitamin C deficiency in the United States: 2003–2004 National Health and Nutrition Examination Survey (NHANES). Am. J. Clin. Nutr. 90(5), 1252–1263 (2009).
  Medline CASGoogle Scholar
• 28. Levine M, Conry-Cantilena C, Wang Y et al. Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc. Natl Acad. Sci. USA 93(8), 3704–3709 (1996).
  Medline CASGoogle Scholar
• 29. Padayatty SJ, Levine M. New insights into the physiology and pharmacology of vitamin C. CMAJ 164(3), 353–355 (2001).
  Medline CASGoogle Scholar
• 30. Harper A, Vijayakumar V, Ouwehand AC et al. Viral infections, the microbiome, and probiotics. Front. Cell. Infect. Microbiol. 10, 596166 (2021).
  MedlineGoogle Scholar
• 31. Menzies V, Jallo N, Kinser P et al. Shared symptoms and putative biological mechanisms in chronic liver disease: implications for biobehavioral research. Biol. Res. Nurs. 17(2), 222–229 (2015).
  MedlineGoogle Scholar
• 32. Quigley EM, Monsour HP. Targeting the microbiota in the management of gastrointestinal and liver disease. Rev. Gastroenterol. Peru 33(2), 139–144 (2013).
  MedlineGoogle Scholar
• 33. Gibson GR, Hutkins R, Sanders ME et al. Expert consensus document: the International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat. Rev. Gastroenterol. Hepatol. 14(8), 491–502 (2017).
  MedlineGoogle Scholar
• 34. Steinert RE, Lee YK, Sybesma W. Vitamins for the gut microbiome. Trends Mol. Med. 26(2), 137–140 (2020).
  Medline CASGoogle Scholar
• 35. Von Martels JZH, Bourgonje AR, Klaassen MaY et al. Riboflavin supplementation in patients with Crohn’s disease (the RISE-UP study). J. Crohns Colitis 14(5), 595–607 (2020).
  MedlineGoogle Scholar
• 36. Schaffler H, Herlemann DP, Klinitzke P et al. Vitamin D administration leads to a shift of the intestinal bacterial composition in Crohn's disease patients, but not in healthy controls. J. Dig. Dis. 19(4), 225–234 (2018).
  MedlineGoogle Scholar
• 37. Shang M, Sun J. Vitamin D/VDR, probiotics, and gastrointestinal diseases. Curr. Med. Chem. 24(9), 876–887 (2017).
  Medline CASGoogle Scholar
• 38. Cantorna MT, McDaniel K, Bora S, Chen J, James J. Vitamin D, immune regulation, the microbiota, and inflammatory bowel disease. Exp. Biol. Med. 239(11), 1524–1530 (2014).
  Google Scholar
• 39. Jostins L, Ripke S, Weersma RK et al. Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491(7422), 119–124 (2012).
  Medline CASGoogle Scholar
• 40. Wang J, Thingholm LB, Skieceviciene J et al. Genome-wide association analysis identifies variation in vitamin D receptor and other host factors influencing the gut microbiota. Nat. Genet. 48(11), 1396–1406 (2016).
  Medline CASGoogle Scholar
• 41. Hazan S, Stollman N, Bozkurt HS et al. Lost microbes of COVID-19: Bifidobacterium, Faecalibacterium depletion and decreased microbiome diversity associated with SARS-CoV-2 infection severity. BMJ Open Gastroenterol. 9(1), e000871 (2022).
  MedlineGoogle Scholar
• 42. Howell MC, Green R, Mcgill AR, Dutta R, Mohapatra S, Mohapatra SS. SARS-CoV-2-Induced gut microbiome dysbiosis: implications for colorectal cancer. Cancers (Basel) 13(11), 2676 (2021).
  Medline CASGoogle Scholar
• 43. Hung YP, Lee CC, Lee JC, Tsai PJ, Ko WC. Gut dysbiosis during COVID-19 and potential effect of probiotics. Microorganisms 9(8), 1605 (2021).
  Medline CASGoogle Scholar
• 44. Yamamoto S, Saito M, Tamura A, Prawisuda D, Mizutani T, Yotsuyanagi H. The human microbiome and COVID-19: a systematic review. PLOS ONE 16(6), e0253293 (2021).
  Medline CASGoogle Scholar
• 45. Zuo T, Wu X, Wen W, Lan P. Gut microbiome alterations in COVID-19. Genomics Proteomics Bioinformatics 19(5), 679–688 (2021).
  MedlineGoogle Scholar
• 46. Patterson T, Isales CM, Fulzele S. Low level of vitamin C and dysregulation of vitamin C transporter might be involved in the severity of COVID-19 infection. Aging Dis. 12(1), 14–26 (2021).
  MedlineGoogle Scholar
• 47. Holford P, Carr AC, Zawari M, Vizcaychipi MP. Vitamin C intervention for critical COVID-19: a pragmatic review of the current level of evidence. Life (Basel) 11(11), 1166 (2021).
  Medline CASGoogle Scholar
• 48. Milani GP, Macchi M, Guz-Mark A. Vitamin C in the treatment of COVID-19. Nutrients 13(4), 1172 (2021).
  Medline CASGoogle Scholar
• 49. Colunga Biancatelli RML, Berrill M, Marik PE. The antiviral properties of vitamin C. Expert Rev. Anti Infect. Ther. 18(2), 99–101 (2020).
  MedlineGoogle Scholar
• 50. Fiorino S, Gallo C, Zippi M et al. Cytokine storm in aged people with CoV-2: possible role of vitamins as therapy or preventive strategy. Aging Clin. Exp. Res. 32(10), 2115–2131 (2020).
  MedlineGoogle Scholar
• 51. Pham VT, Fehlbaum S, Seifert N et al. Effects of colon-targeted vitamins on the composition and metabolic activity of the human gut microbiome – a pilot study. Gut Microbes 13(1), 1–20 (2021).
  MedlineGoogle Scholar
• 52. Rawat D, Roy A, Maitra S, Gulati A, Khanna P, Baidya DK. Vitamin C and COVID-19 treatment: a systematic review and meta-analysis of randomized controlled trials. Diabetes Metab. Syndr. 15(6), 102324 (2021).
  MedlineGoogle Scholar
• 53. Levy M, Kolodziejczyk AA, Thaiss CA, Elinav E. Dysbiosis and the immune system. Nat. Rev. Immunol. 17(4), 219–232 (2017).
  Medline CASGoogle Scholar
• 54. O’Callaghan A, Van Sinderen D. Bifidobacteria and their role as members of the human gut microbiota. Front. Microbiol. 7, 925 (2016).
  MedlineGoogle Scholar
• 55. Ruiz L, Delgado S, Ruas-Madiedo P, Sánchez B, Margolles A. Bifidobacteria and their molecular communication with the immune system. Front. Microbiol. 8, 2345 (2017). • Good review on the role of Bifidobacteria in immunity.
  MedlineGoogle Scholar
• 56. Xu K, Cai H, Shen Y et al. [Management of corona virus disease-19 (COVID-19): the Zhejiang experience]. Zhejiang Da Xue Xue Bao Yi Xue Ban 49(1), 147–157 (2020).
  MedlineGoogle Scholar
• 57. Yeoh YK, Zuo T, Lui GCY et al. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut 70(4), 698–706 (2021).
  Medline CASGoogle Scholar
• 58. Papoutsis A, Borody T, Dolai S et al. Detection of SARS-CoV-2 from patient fecal samples by whole genome sequencing. Gut Pathog. 13(1), 7 (2021).
  Medline CASGoogle Scholar
• 59. Wagner BD, Grunwald GK, Zerbe GO et al. On the use of diversity measures in longitudinal sequencing studies of microbial communities. Front. Microbiol. 9, 1037 (2018).
  MedlineGoogle Scholar
• 60. Otten AT, Bourgonje AR, Peters V, Alizadeh BZ, Dijkstra G, Harmsen HJM. Vitamin C supplementation in healthy individuals leads to shifts of bacterial populations in the gut – a pilot study. Antioxidants (Basel) 10(8), 1278 (2021). •• This is the study closest to ours, with similar findings.
  Medline CASGoogle Scholar
• 61. Garaiova I, Muchová J, Nagyová Z et al. Probiotics and vitamin C for the prevention of respiratory tract infections in children attending preschool: a randomised controlled pilot study. Eur. J. Clin. Nutr. 69(3), 373–379 (2015).
  Medline CASGoogle Scholar
• 62. De Vrese M, Winkler P, Rautenberg P et al. Effect of Lactobacillus gasseri PA 16/8, Bifidobacterium longum SP 07/3, B. bifidum MF 20/5 on common cold episodes: a double blind, randomized, controlled trial. Clin. Nutr. 24(4), 481–491 (2005).
  MedlineGoogle Scholar
• 63. King CH, Desai H, Sylvetsky AC et al. Baseline human gut microbiota profile in healthy people and standard reporting template. PLOS ONE 14(9), e0206484 (2019).
  Medline CASGoogle Scholar
• 64. Xiao M, Xu P, Zhao J et al. Oxidative stress-related responses of Bifidobacterium longum subsp. longum BBMN68 at the proteomic level after exposure to oxygen. Microbiology 157(Pt 6), 1573–1588 (2011).
  Medline CASGoogle Scholar
• 65. Marras L, Caputo M, Bisicchia S et al. The role of Bifidobacteria in predictive and preventive medicine: a focus on eczema and hypercholesterolemia. Microorganisms 9(4), 836 (2021).
  Medline CASGoogle Scholar
• 66. Fukuda S, Toh H, Hase K et al. Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature 469(7331), 543–547 (2011).
  Medline CASGoogle Scholar
• 67. Yasui H, Kiyoshima J, Hori T, Shida K. Protection against influenza virus infection of mice fed Bifidobacterium breve YIT4064. Clin. Diagn. Lab. Immunol. 6(2), 186–192 (1999).
  Medline CASGoogle Scholar
• 68. Mahooti M, Abdolalipour E, Salehzadeh A, Mohebbi SR, Gorji A, Ghaemi A. Immunomodulatory and prophylactic effects of Bifidobacterium bifidum probiotic strain on influenza infection in mice. World J. Microbiol. Biotechnol. 35(6), 91 (2019).
  MedlineGoogle Scholar
• 69. Zhang Q, Hu J, Feng JW et al. Influenza infection elicits an expansion of gut population of endogenous Bifidobacterium animalis which protects mice against infection. Genome Biol. 21(1), 99 (2020).
  MedlineGoogle Scholar
• 70. Namba K, Hatano M, Yaeshima T, Takase M, Suzuki K. Effects of Bifidobacterium longum BB536 administration on influenza infection, influenza vaccine antibody titer, and cell-mediated immunity in the elderly. Biosci. Biotechnol. Biochem. 74(5), 939–945 (2010).
  Medline CASGoogle Scholar
• 71. Darbandi A, Asadi A, Ghanavati R et al. The effect of probiotics on respiratory tract infection with special emphasis on COVID-19: systemic review 2010–20. Int. J. Infect. Dis. 105, 91–104 (2021).
  Medline CASGoogle Scholar
• 72. Kurian SJ, Unnikrishnan MK, Miraj SS et al. Probiotics in prevention and treatment of COVID-19: current perspective and future prospects. Arch. Med. Res. 52(6), 582–594 (2021).
  Medline CASGoogle Scholar
• 73. Olaimat AN, Aolymat I, Al-Holy M et al. The potential application of probiotics and prebiotics for the prevention and treatment of COVID-19. NPJ Sci. Food 4, 17 (2020).
  MedlineGoogle Scholar
• 74. Shu G, Yang H, Tao Q, He C. Effect of ascorbic acid and cysteine hydrochloride on growth of Bifidobacterium bifidum 1, 2. Adv. J. Food Sci.Technol. 5(6), 678–681 (2013). •• This study has similar findings to ours, in an in vitro model system.
  CASGoogle Scholar
• 75. Khan MT, Browne WR, Van Dijl JM, Harmsen HJM. How can Faecalibacterium prausnitzii employ riboflavin for extracellular electron transfer? Antioxid. Redox Signal. 17(10), 1433–1440 (2012).
  Medline CASGoogle Scholar
• 76. Khan MT, Duncan SH, Stams AJM, Van Dijl JM, Flint HJ, Harmsen HJM. The gut anaerobe Faecalibacterium prausnitzii uses an extracellular electron shuttle to grow at oxic-anoxic interphases. ISME J. 6(8), 1578–1585 (2012).
  Medline CASGoogle Scholar
• 77. Million M, Raoult D. Linking gut redox to human microbiome. Hum. Microbiome J. 10, 27–32 (2018).
  Google Scholar
• 78. Million M, Tidjani Alou M, Khelaifia S et al. Increased gut redox and depletion of anaerobic and methanogenic prokaryotes in severe acute malnutrition. Sci. Rep. 6, 26051 (.2016).
  Medline CASGoogle Scholar
• 79. Sokol H, Pigneur B, Watterlot L et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc. Natl Acad. Sci. USA 105(43), 16731–16736 (2008).
  Medline CASGoogle Scholar
• 80. Parrow NL, Leshin JA, Levine M. Parenteral ascorbate as a cancer therapeutic: a reassessment based on pharmacokinetics. Antioxid. Redox Signal. 19(17), 2141–2156 (2013).
  Medline CASGoogle Scholar
• 81. Padayatty SJ, Levine M. Vitamin C: the known and the unknown and Goldilocks. Oral Dis. 22(6), 463–493 (2016).
  Medline CASGoogle Scholar
• 82. Vacca M, Celano G, Calabrese FM, Portincasa P, Gobbetti M, De Angelis M. The controversial role of human gut Lachnospiraceae. Microorganisms 8(4), 573 (2020).
  Medline CASGoogle Scholar
• 83. Pickard JM, Zeng MY, Caruso R, Núñez G. Gut microbiota: role in pathogen colonization, immune responses, and inflammatory disease. Immunol. Rev. 279(1), 70–89 (2017).
  Medline CASGoogle Scholar
• 84. Hoffer LJ, Levine M, Assouline S et al. Phase I clinical trial of i.v. ascorbic acid in advanced malignancy. Ann. Oncol. 19(11), 1969–1974 (2008).
  Medline CASGoogle Scholar
• 85. Padayatty SJ, Sun H, Wang Y et al. Vitamin C pharmacokinetics: implications for oral and intravenous use. Ann. Intern. Med. 140(7), 533–537 (2004).
  Medline CASGoogle Scholar
• 86. Graumlich JF, Ludden TM, Conry-Cantilena C, Cantilena LR Jr, Wang Y, Levine M. Pharmacokinetic model of ascorbic acid in healthy male volunteers during depletion and repletion. Pharm. Res. 14(9), 1133–1139 (1997).
  Medline CASGoogle Scholar
• 87. Hoffman FA. Micronutrient requirements of cancer patients. Cancer 55(Suppl. 1), 295–300 (1985).
  Medline CASGoogle Scholar
• 88. Khanzode SD, Dakhale GN, Khanzode SS, Saoji A, Palasodkar R. Oxidative damage and major depression: the potential antioxidant action of selective serotonin re-uptake inhibitors. Redox Rep. 8(6), 365–370 (2003).
  Medline CASGoogle Scholar
• 89. Mikirova N, Casciari J, Riordan N, Hunninghake R. Clinical experience with intravenous administration of ascorbic acid: achievable levels in blood for different states of inflammation and disease in cancer patients. J. Transl. Med. 11, 191 (2013).
  Medline CASGoogle Scholar
• 90. Mikirova N, Casciari J, Rogers A, Taylor P. Effect of high-dose intravenous vitamin C on inflammation in cancer patients. J. Transl. Med. 10, 189 (2012).
  Medline CASGoogle Scholar
• 91. Lee T, Clavel T, Smirnov K et al. Oral versus intravenous iron replacement therapy distinctly alters the gut microbiota and metabolome in patients with IBD. Gut 66(5), 863–871 (2017).
  Medline CASGoogle Scholar
• 92. Liu H, Wu W, Luo Y. Oral and intravenous iron treatment alter the gut microbiome differentially in dialysis patients. Int. Urol. Nephrol. doi:10.1007/s11255-022-03377-0 (.2022) (Epub ahead of print).
  Google Scholar
• 93. Durazzi F, Sala C, Castellani G, Manfreda G, Remondini D, De Cesare A. Comparison between 16S rRNA and shotgun sequencing data for the taxonomic characterization of the gut microbiota. Sci. Rep. 11( 1), 3030 (2021).
  Medline CASGoogle Scholar