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Published in: Inflammopharmacology 1/2013

01-02-2013 | Research Article

Green-lipped mussel extract (Perna canaliculus) and glucosamine sulphate in patients with knee osteoarthritis: therapeutic efficacy and effects on gastrointestinal microbiota profiles

Authors: Samantha Coulson, Henry Butt, Phillip Vecchio, Helen Gramotnev, Luis Vitetta

Published in: Inflammopharmacology | Issue 1/2013

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Abstract

Objective

To investigate how changes in the gastrointestinal tract (GIT) microbiota profile may influence nutraceutical efficacy in osteoarthritis (OA) and allow the formulation of a hypothesis that explains in part the inconsistent and contentious findings from OA clinical studies with green-lipped mussel (GLM) and glucosamine.

Methods

A non-blinded randomised clinical trial was conducted with 38 subjects diagnosed with knee OA. Each participant received either 3,000 mg/day of a whole GLM extract or 3,000 mg/day of glucosamine sulphate (GS), p.o. for 12 weeks. Faecal microbial analyses were carried out after collecting stools at T 0 and T 12 weeks. Additional pharmacometric measures were obtained from changes in arthritic scores in the Western Ontario McMaster Universities Arthritis Index (WOMAC) and the Lequesne algofunctional indices and the Gastrointestinal Symptom Rating Scale (GSRS). An intention-to-treat analysis was employed and participant data collected at T 0, T 6 and T 12 weeks.

Results

There were no statistically significant changes in bacterial growth patterns determined by the Wilcoxon test. In both groups there was a trend towards a decrease in Clostridium and Staphylococcus species and increase in Lactobacillus, Streptococcus and Eubacterium species. In the GLM group Bifidobacterium tended to increase and Enterococcus and yeast species to decrease. The GS-treated group demonstrated a trend towards a decrease in Bacteroides and an increase in yeasts and Coliforms species, most notably Escherichia coli. We further confirm significant improvement (p < 0.05) in all OA outcome measures from T 0 to T 12 weeks for both the GLM and GS groups. The GSRS scores indicated that GIT function significantly improved over the 12 weeks duration with GLM and GS supplementation.

Conclusion

Both GLM and GS reduced OA symptoms and non-significantly altered the gut microbiota profile from baseline. Changes in the microbiota profiles occurred in both treatment groups; the most notable being a reduction in the Clostridia sp. This study suggests that nutritional supplements such as GLM and GS may regulate some of the metabolic and immunological activities of the GIT microbiota. The decrease in Clostridia, a potent modulator of colonic Th17 and CD4+ regulatory T cells, was consistent with a decrease in inflammation; improved GSRS scores and OA symptoms for these OA participants. The GIT microbiota may be important factor in the first-pass metabolism of these nutraceuticals.
Literature
go back to reference Aghazadeh-Habashi A, Sattari S, Pasutto F, Jamali F (2002) Single dose pharmacokinetics and bioavailability of glucosamine in the rat. J Pharm Pharm Sci 5(2):181–184PubMed Aghazadeh-Habashi A, Sattari S, Pasutto F, Jamali F (2002) Single dose pharmacokinetics and bioavailability of glucosamine in the rat. J Pharm Pharm Sci 5(2):181–184PubMed
go back to reference Altman R, Ach E, Bloch D et al (1986) Development of criteria for the classification and reporting of osteoarthritis: classification of osteoarthritis of the knee. Arthr Rheum 29(8):1039–1049CrossRef Altman R, Ach E, Bloch D et al (1986) Development of criteria for the classification and reporting of osteoarthritis: classification of osteoarthritis of the knee. Arthr Rheum 29(8):1039–1049CrossRef
go back to reference Atarashi K, Tanoue T, Shima T et al (2011) Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331(6015):337–341PubMedCrossRef Atarashi K, Tanoue T, Shima T et al (2011) Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331(6015):337–341PubMedCrossRef
go back to reference Barnes MJ, Powrie F (2011) Immunology. The gut’s Clostridium cocktail. Science 331(6015):289–290PubMedCrossRef Barnes MJ, Powrie F (2011) Immunology. The gut’s Clostridium cocktail. Science 331(6015):289–290PubMedCrossRef
go back to reference Bellamy N (2002) WOMAC: a 20-year experiential review of a patient-centred self-reported health status questionnaire. J Rheumatol 29(12):2473–2476PubMed Bellamy N (2002) WOMAC: a 20-year experiential review of a patient-centred self-reported health status questionnaire. J Rheumatol 29(12):2473–2476PubMed
go back to reference Bellamy N, Buchanan W, Goldsmith CH et al (1988) Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to anti-rheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 15:1833–1840PubMed Bellamy N, Buchanan W, Goldsmith CH et al (1988) Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to anti-rheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 15:1833–1840PubMed
go back to reference Bjordal J, Ljunggren AE, Klovning A, Slordal L (2004) Non-steroidal anti-inflammatory drugs, including cyclo-oxygenase-2 inhibitors, in osteoarthritis knee: meta-analysis of randomised placebo controlled trials. Br Med J 329(7478):1317–1322CrossRef Bjordal J, Ljunggren AE, Klovning A, Slordal L (2004) Non-steroidal anti-inflammatory drugs, including cyclo-oxygenase-2 inhibitors, in osteoarthritis knee: meta-analysis of randomised placebo controlled trials. Br Med J 329(7478):1317–1322CrossRef
go back to reference Brien S, Prescott P, Coghlan B et al (2008) Systematic review of the nutritional supplement Perna Canaliculus (green-lipped mussel) in the treatment of osteoarthritis. Q J Med 101(3):167–179CrossRef Brien S, Prescott P, Coghlan B et al (2008) Systematic review of the nutritional supplement Perna Canaliculus (green-lipped mussel) in the treatment of osteoarthritis. Q J Med 101(3):167–179CrossRef
go back to reference Chitturi S, George J (2002) Hepatotoxicity of commonly used drugs: nonsteroidal anti-inflammatory drugs, antihypertensives, antidiabetic agents, anticonvulsants, lipid-lowering agents, psychotropic drugs. Semin Liver Dis 22(2):169–183PubMedCrossRef Chitturi S, George J (2002) Hepatotoxicity of commonly used drugs: nonsteroidal anti-inflammatory drugs, antihypertensives, antidiabetic agents, anticonvulsants, lipid-lowering agents, psychotropic drugs. Semin Liver Dis 22(2):169–183PubMedCrossRef
go back to reference Chong V, Wang C (2008) Higher prevalence of gastrointestinal symptoms among patients with rheumatic disorders. Singap Med J 49(5):419–424 Chong V, Wang C (2008) Higher prevalence of gastrointestinal symptoms among patients with rheumatic disorders. Singap Med J 49(5):419–424
go back to reference Coulson S, Vecchio P, Gramotnev H, Vitetta L (2012) Green-lipped mussel (Perna canaliculus) extract efficacy in knee osteoarthritis and improvement in gastrointestinal dysfunction: a pilot study. Inflammopharmacology 20(2):71–76PubMedCrossRef Coulson S, Vecchio P, Gramotnev H, Vitetta L (2012) Green-lipped mussel (Perna canaliculus) extract efficacy in knee osteoarthritis and improvement in gastrointestinal dysfunction: a pilot study. Inflammopharmacology 20(2):71–76PubMedCrossRef
go back to reference Egert M, de Graaf AA, Smidt H et al (2006) Beyond diversity: functional microbiomics of the human colon. Trends Microbiol 14:86–91PubMedCrossRef Egert M, de Graaf AA, Smidt H et al (2006) Beyond diversity: functional microbiomics of the human colon. Trends Microbiol 14:86–91PubMedCrossRef
go back to reference Ernst E (1998) Usage of complementary therapies in rheumatology: a systematic review. Clin Rheumatol 17:301–305PubMedCrossRef Ernst E (1998) Usage of complementary therapies in rheumatology: a systematic review. Clin Rheumatol 17:301–305PubMedCrossRef
go back to reference Foley S, Stolarczyk E, Mouni F et al (2008) Characterisation of glutamine fructose-6-phosphate amidotransferase (EC 2.6.1.16) and N-acetylglucosamine metabolism in Bifidobacterium. Arch Microbiol 189(2):157–167PubMedCrossRef Foley S, Stolarczyk E, Mouni F et al (2008) Characterisation of glutamine fructose-6-phosphate amidotransferase (EC 2.6.1.16) and N-acetylglucosamine metabolism in Bifidobacterium. Arch Microbiol 189(2):157–167PubMedCrossRef
go back to reference Gaboriau-Routhiau V, Rakotobe S, Lécuyer E et al (2009) The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity 31(4):677–689PubMedCrossRef Gaboriau-Routhiau V, Rakotobe S, Lécuyer E et al (2009) The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity 31(4):677–689PubMedCrossRef
go back to reference Garcia Rodriguez LA, Hernandez-Diaz S (2001) Relative risk of upper gastrointestinal complications among users of acetaminophen and nonsteroidal anti-inflammatory drugs. Epidemiology 12(5):570–576PubMedCrossRef Garcia Rodriguez LA, Hernandez-Diaz S (2001) Relative risk of upper gastrointestinal complications among users of acetaminophen and nonsteroidal anti-inflammatory drugs. Epidemiology 12(5):570–576PubMedCrossRef
go back to reference Gillett R, Norrell A (2011) Considerations for safe use of statins: liver enzyme abnormalities and muscle toxicity. Am Fam Physician 83(6):711–716PubMed Gillett R, Norrell A (2011) Considerations for safe use of statins: liver enzyme abnormalities and muscle toxicity. Am Fam Physician 83(6):711–716PubMed
go back to reference Holzapfel W, Haberer P, Snel J et al (1998) Overview of gut flora and probiotics. Int J Food Microbiol 41:85–101PubMedCrossRef Holzapfel W, Haberer P, Snel J et al (1998) Overview of gut flora and probiotics. Int J Food Microbiol 41:85–101PubMedCrossRef
go back to reference Kelly D, Conway S, Aminov R (2005) Commensal gut bacteria: mechanisms of immune modulation. Trends Immunol 26(6):326–333PubMedCrossRef Kelly D, Conway S, Aminov R (2005) Commensal gut bacteria: mechanisms of immune modulation. Trends Immunol 26(6):326–333PubMedCrossRef
go back to reference Koser S, Tribby I, Stuedell J (1961) Glucosamine utilization by some lactic acid bacteria. J Infect Dis 108:324–332PubMedCrossRef Koser S, Tribby I, Stuedell J (1961) Glucosamine utilization by some lactic acid bacteria. J Infect Dis 108:324–332PubMedCrossRef
go back to reference Laparra JM, Sanz Y (2010) Interactions of gut microbiota with functional food components and nutraceuticals. Pharmacol Res 61(3):219–225PubMedCrossRef Laparra JM, Sanz Y (2010) Interactions of gut microbiota with functional food components and nutraceuticals. Pharmacol Res 61(3):219–225PubMedCrossRef
go back to reference Lequesne MG, Mery C, Samson M, Gerard P (1987) Indexes of severity for osteoarthritis of the hip and knee validation-value in comparison with other assessment tests. Scand J Rheumatol 65:85–89CrossRef Lequesne MG, Mery C, Samson M, Gerard P (1987) Indexes of severity for osteoarthritis of the hip and knee validation-value in comparison with other assessment tests. Scand J Rheumatol 65:85–89CrossRef
go back to reference Lutwak-Mann C (1941) Enzymatic decomposition of amino-sugars. Biochem J 35(5):610–626PubMed Lutwak-Mann C (1941) Enzymatic decomposition of amino-sugars. Biochem J 35(5):610–626PubMed
go back to reference Reginster JY (2002) The prevalence and burden of arthritis. Rheumatology (Oxford) 41(Supp 1):3–6CrossRef Reginster JY (2002) The prevalence and burden of arthritis. Rheumatology (Oxford) 41(Supp 1):3–6CrossRef
go back to reference Rutjes A, Nüesch E, Reichenbach S, Jüni P (2008) S-Adenosylmethionine for osteoarthritis of the knee or hip. Cochrane Database Syst Rev 4:CD007321 Rutjes A, Nüesch E, Reichenbach S, Jüni P (2008) S-Adenosylmethionine for osteoarthritis of the knee or hip. Cochrane Database Syst Rev 4:CD007321
go back to reference Smith K, McCoy KD, Macpherson AJ (2007) Use of axenic animals in studying the adaptation of mammals to their commensal intestinal microbiota. Semin Immunol 19(2):59–69PubMedCrossRef Smith K, McCoy KD, Macpherson AJ (2007) Use of axenic animals in studying the adaptation of mammals to their commensal intestinal microbiota. Semin Immunol 19(2):59–69PubMedCrossRef
go back to reference Stepankova R, Powrie F, Kofronova O et al (2007) Segmented filamentous bacteria in a defined bacterial cocktail induce intestinal inflammation in SCID mice reconstituted with CD45RBhigh CD4+ T cells. Inflamm Bowel Dis 13(10):1202–1211PubMedCrossRef Stepankova R, Powrie F, Kofronova O et al (2007) Segmented filamentous bacteria in a defined bacterial cocktail induce intestinal inflammation in SCID mice reconstituted with CD45RBhigh CD4+ T cells. Inflamm Bowel Dis 13(10):1202–1211PubMedCrossRef
go back to reference Svedlund J, Sjodin I, Dotevall G (1988) GSRS: a clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcer disease. Dig Dis Sci 33:129–134PubMedCrossRef Svedlund J, Sjodin I, Dotevall G (1988) GSRS: a clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcer disease. Dig Dis Sci 33:129–134PubMedCrossRef
go back to reference Tana C, Umesaki Y, Imaoka A et al (2010) Altered profiles of intestinal microbiota and organic acids may be the origin of symptoms in irritable bowel syndrome. Neurogastroenterol Motil 22(5):512–519, e114–e115 Tana C, Umesaki Y, Imaoka A et al (2010) Altered profiles of intestinal microbiota and organic acids may be the origin of symptoms in irritable bowel syndrome. Neurogastroenterol Motil 22(5):512–519, e114–e115
go back to reference Thrupp L (1980) Susceptibility testing of antibiotics in liquid media. In: Lorian V (ed) Antibiotics in laboratory medicine, chap 4. Williams & Wilkins pub, Baltimore, pp 73–113 Thrupp L (1980) Susceptibility testing of antibiotics in liquid media. In: Lorian V (ed) Antibiotics in laboratory medicine, chap 4. Williams & Wilkins pub, Baltimore, pp 73–113
go back to reference Towheed T, Maxwell L, Anastassiades TP et al (2005) Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev 2:CD002946 Towheed T, Maxwell L, Anastassiades TP et al (2005) Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev 2:CD002946
go back to reference Tucker G, Adams R, Wilson D (2010) New Australian population scoring coefficients for the old version of the SF-36 and SF-12 health status questionnaires. Qual Life Res 19:1069–1076PubMedCrossRef Tucker G, Adams R, Wilson D (2010) New Australian population scoring coefficients for the old version of the SF-36 and SF-12 health status questionnaires. Qual Life Res 19:1069–1076PubMedCrossRef
go back to reference Ulbricht C, Chao W, Costa D et al (2009) An evidence-based systematic review of green-lipped mussel (Perna canaliculus) by the Natural Standard Research Collaboration. J Diet Suppl 6(1):54–90PubMedCrossRef Ulbricht C, Chao W, Costa D et al (2009) An evidence-based systematic review of green-lipped mussel (Perna canaliculus) by the Natural Standard Research Collaboration. J Diet Suppl 6(1):54–90PubMedCrossRef
go back to reference Umesaki Y, Setoyama H, Matsumoto S et al (1999) Differential roles of segmented filamentous bacteria and clostridia in development of the intestinal immune system. Infect Immun 67:3504–3511PubMed Umesaki Y, Setoyama H, Matsumoto S et al (1999) Differential roles of segmented filamentous bacteria and clostridia in development of the intestinal immune system. Infect Immun 67:3504–3511PubMed
go back to reference Vitetta L, Briskey D, Hayes E et al (2012) A review of the pharmacobiotic regulation of gastrointestinal inflammation by probiotics, commensal bacteria and prebiotics. Inflammopharmacology (Epub ahead of print) Vitetta L, Briskey D, Hayes E et al (2012) A review of the pharmacobiotic regulation of gastrointestinal inflammation by probiotics, commensal bacteria and prebiotics. Inflammopharmacology (Epub ahead of print)
go back to reference Wandel S, Juni P, Tendal B et al (2010) Effects of glucosamine, chondroitin or placebo in patients with osteoarthritis of hip or knee: network meta-analysis. BMJ 341:c4675PubMedCrossRef Wandel S, Juni P, Tendal B et al (2010) Effects of glucosamine, chondroitin or placebo in patients with osteoarthritis of hip or knee: network meta-analysis. BMJ 341:c4675PubMedCrossRef
go back to reference Ware J, Kosinski M, Keller S (1996) A 12-item short-form health survey: construction of scales and preliminary tests of reliability and validity. Med Care 34(3):220–233PubMedCrossRef Ware J, Kosinski M, Keller S (1996) A 12-item short-form health survey: construction of scales and preliminary tests of reliability and validity. Med Care 34(3):220–233PubMedCrossRef
go back to reference Willis A (2007) Anaerobic culture methods, in anaerobic microbiology: a practical approach. IRL Press at Oxford University Press, Oxford Willis A (2007) Anaerobic culture methods, in anaerobic microbiology: a practical approach. IRL Press at Oxford University Press, Oxford
go back to reference Wolfe J, Nakada H (1956) Glucosamine degradation by Escherichia coli. II. The isomeric conversion of glucosamine 6-PO4 to fructose 6-PO4 and ammonia. Arch Biochem Biophys 64(2):489–497PubMedCrossRef Wolfe J, Nakada H (1956) Glucosamine degradation by Escherichia coli. II. The isomeric conversion of glucosamine 6-PO4 to fructose 6-PO4 and ammonia. Arch Biochem Biophys 64(2):489–497PubMedCrossRef
go back to reference Wolfe J, Morita R, Nakada H (1956) Glucosamine degradation by Escherichia coli, I. Observations with resting cells and dry-cell preparations. Arch Biochem Biophys 64:480–488PubMedCrossRef Wolfe J, Morita R, Nakada H (1956) Glucosamine degradation by Escherichia coli, I. Observations with resting cells and dry-cell preparations. Arch Biochem Biophys 64:480–488PubMedCrossRef
go back to reference Wolfe F, Kong S, Watson D (2000) Gastrointestinal symptoms and health related quality of life in patients with arthritis. J Rheumatol 27(6):1373–1378PubMed Wolfe F, Kong S, Watson D (2000) Gastrointestinal symptoms and health related quality of life in patients with arthritis. J Rheumatol 27(6):1373–1378PubMed
go back to reference Woolf AD, Pfleger B (2003) Burden of major musculoskeletal conditions. Bull World Health Organ 81(9):646–656PubMed Woolf AD, Pfleger B (2003) Burden of major musculoskeletal conditions. Bull World Health Organ 81(9):646–656PubMed
go back to reference Wu H, Ivanov I, Darce J et al (2010) Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity 32(6):815–827PubMedCrossRef Wu H, Ivanov I, Darce J et al (2010) Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity 32(6):815–827PubMedCrossRef
Metadata
Title
Green-lipped mussel extract (Perna canaliculus) and glucosamine sulphate in patients with knee osteoarthritis: therapeutic efficacy and effects on gastrointestinal microbiota profiles
Authors
Samantha Coulson
Henry Butt
Phillip Vecchio
Helen Gramotnev
Luis Vitetta
Publication date
01-02-2013
Publisher
SP Birkhäuser Verlag Basel
Published in
Inflammopharmacology / Issue 1/2013
Print ISSN: 0925-4692
Electronic ISSN: 1568-5608
DOI
https://doi.org/10.1007/s10787-012-0146-4

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