TY - JOUR
T1 - A Sustained-Release Butyrate Tablet Suppresses Ex Vivo T Helper Cell Activation of Osteoarthritis Patients in a Double-Blind Placebo-Controlled Randomized Trial
AU - Korsten, Sandra G.P.J.
AU - Hartog, Merel
AU - Berends, Alinda J.
AU - Koenders, Marije I.
AU - Popa, Calin D.
AU - Vromans, Herman
AU - Garssen, Johan
AU - van de Ende, Cornelia H.M.
AU - Vermeiden, Jan P.W.
AU - Willemsen, Linette E.M.
N1 - Publisher Copyright:
© 2024 by the authors.
PY - 2024/10
Y1 - 2024/10
N2 - Degenerative joint disease osteoarthritis (OA) is characterized by the degeneration of cartilage, synovial inflammation and low-grade systemic inflammation in association with microbial dysbiosis and intestinal barrier defects. Butyrate is known for its anti-inflammatory and barrier protective effects and might benefit OA patients. In a double-blind placebo-controlled randomized trial, the effects of four to five weeks of oral treatment with sustained-release (SR) butyrate tablets (600 mg/day) on systemic inflammation and immune function were studied in hand OA patients. Serum markers for systemic inflammation and lipopolysaccharide (LPS) leakage were measured and ex vivo stimulation of whole blood or peripheral blood mononuclear cells (PBMCs) was performed at baseline and after treatment. Butyrate treatment did not affect the serum markers nor the cytokine release of ex vivo LPS-stimulated whole blood or PBMCs nor the phenotype of restimulated monocytes. By contrast, butyrate treatment reduced the percentage of activated T helper (Th) cells and the Th17/Treg ratio in αCD3/CD28-activated PBMCs, though cytokine release upon stimulation remained unaffected. Nevertheless, the percentage of CD4+IL9+ cells was reduced by butyrate as compared to the placebo. In both groups, the frequency of Th1, Treg, Th17, activated Th17, CD4+IFNγ+ and CD4+TNFα+ cells was reduced. This study shows a proof of principle of some immunomodulatory effects using a SR butyrate treatment in hand OA patients. The inflammatory phenotype of Th cells was reduced, as indicated by a reduced percentage of Th9 cells, activated Th cells and improved Th17/Treg balance in ex vivo αCD3/CD28-activated PBMCs. Future studies are warranted to further optimize the butyrate dose regime to ameliorate inflammation in OA patients.
AB - Degenerative joint disease osteoarthritis (OA) is characterized by the degeneration of cartilage, synovial inflammation and low-grade systemic inflammation in association with microbial dysbiosis and intestinal barrier defects. Butyrate is known for its anti-inflammatory and barrier protective effects and might benefit OA patients. In a double-blind placebo-controlled randomized trial, the effects of four to five weeks of oral treatment with sustained-release (SR) butyrate tablets (600 mg/day) on systemic inflammation and immune function were studied in hand OA patients. Serum markers for systemic inflammation and lipopolysaccharide (LPS) leakage were measured and ex vivo stimulation of whole blood or peripheral blood mononuclear cells (PBMCs) was performed at baseline and after treatment. Butyrate treatment did not affect the serum markers nor the cytokine release of ex vivo LPS-stimulated whole blood or PBMCs nor the phenotype of restimulated monocytes. By contrast, butyrate treatment reduced the percentage of activated T helper (Th) cells and the Th17/Treg ratio in αCD3/CD28-activated PBMCs, though cytokine release upon stimulation remained unaffected. Nevertheless, the percentage of CD4+IL9+ cells was reduced by butyrate as compared to the placebo. In both groups, the frequency of Th1, Treg, Th17, activated Th17, CD4+IFNγ+ and CD4+TNFα+ cells was reduced. This study shows a proof of principle of some immunomodulatory effects using a SR butyrate treatment in hand OA patients. The inflammatory phenotype of Th cells was reduced, as indicated by a reduced percentage of Th9 cells, activated Th cells and improved Th17/Treg balance in ex vivo αCD3/CD28-activated PBMCs. Future studies are warranted to further optimize the butyrate dose regime to ameliorate inflammation in OA patients.
KW - butyrate
KW - intestinal barrier
KW - low-grade inflammation
KW - non-communicable diseases
KW - osteoarthritis
KW - short-chain fatty acid
UR - http://www.scopus.com/inward/record.url?scp=85206558352&partnerID=8YFLogxK
U2 - 10.3390/nu16193384
DO - 10.3390/nu16193384
M3 - Article
C2 - 39408351
AN - SCOPUS:85206558352
SN - 2072-6643
VL - 16
JO - Nutrients
JF - Nutrients
IS - 19
M1 - 3384
ER -