Lactobacillus acidophilus NCFM affects colonic mucosal opioid receptor expression in patients with functional abdominal pain - a randomised clinical study.
BACKGROUND
In a recent double-blinded clinical trial, the probiotic combination of Lactobacillus acidophilus NCFM (L-NCFM) and B-LBi07 reduced bloating symptoms in patients with functional bowel disorders; an effect more evident in those who reported abdominal pain. In mice, L-NCFM but not B-LBi07 induced colonic mu-opioid receptor (MOR) and cannabinoid receptor 2 (CB2) expression, and reduced visceral sensitivity.


OBJECTIVE
To determine if L-NCFM was the active component in the clinical trial and to investigate the mechanism of action in humans with mild to moderate abdominal pain.


METHODS
Caucasian women (n = 20) 18-70 years with mild to moderate abdominal pain were enrolled in a double-blind, two-armed, single-centre study. Patients were given either L-NCFM alone or in combination with B-LBi07 for 21 days at a total dose of 2 × 10(10) CFU b.d. Colonic biopsies were collected during unsedated, unprepped flexible sigmoidoscopy before and at the end of probiotic consumption. mRNA and immunostaining were then performed on these biopsies. Patients kept symptom diaries for the 7 days prior to starting probiotic therapy and for the last 7 days of therapy.


RESULTS
L-NCFM alone, but not with B-LBi07, induced colonic MOR mRNA and protein expression, as well as downstream signalling, as measured by enterocyte STAT3-phosphorylation. In contrast, CB2 expression was decreased. Both treatment groups trended towards improvement in symptoms, but the study was insufficiently powered to draw meaningful conclusions.


CONCLUSIONS
Lactobacillus acidophilus NCFM modulates mu-opioid receptor expression and activity, while the combination of L-NCFM and B-LBi07 does not. This study provides a possible mechanism for action by which probiotics modulates pain sensation in humans (Clinical Trial Number: NCT01064661).
Department of Maternal and Child Health, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
T
T
Ringel-Kulka
J R
JR
Goldsmith
I M
IM
Carroll
S P
SP
Barros
O
O
Palsson
C
C
Jobin
Y
Y
Ringel
D015746:Abdominal Pain / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D003106:Colon / Q000378:metabolism / Q000473:pathology; D004311:Double-Blind Method; D020895:Enterocytes / Q000378:metabolism; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D007779:Lactobacillus acidophilus; D008875:Middle Aged; D019936:Probiotics / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics; D017450:Receptors, Opioid, mu / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D055815:Young Adult
D012333:RNA, Messenger; D043885:Receptor, Cannabinoid, CB2; D017450:Receptors, Opioid, mu; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human