2016年10月21日
トクホの「お腹の調子を整える」の基本的コンセプトは、
発酵で増加する短鎖脂肪酸が、腸に良い影響を与えるというものである。
そのため、発酵でガスが増えようが、腹痛になろうが、浸透圧性下痢を生じようが、
それなりの利益があるという考えも出来なくはない。
しかし、
実際の最先端研究では、「短鎖脂肪酸が腸に良いという理論」自体、
否定、あるいは疑問視されている。
これまで、酸酸とプロピオン酸がＩＢＳにとって悪玉であるという論文を紹介したが、
短鎖脂肪酸のなかでも酪酸だけは、腸にいいのではないか？という見解がある。
しかし、酪酸においても、
腸にいいのか、悪いのか、結論は出ていないのが現状である。
ひとつの考え方として、ワシントン大学の研究者は、
「少量はいいが、大量は悪い」
という考えを提示している。
Neurogastroenterol
Motil. 2011 Nov;23(11):975-9. doi:
10.1111/j.1365-2982.2011.01775.x.
Colonic butyrate-
algesic or analgesic?
Kannampalli P1, Shaker R, Sengupta JN.
·
1Division
of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, WI
53226, USA. sengupta@mcw.edu
Abstract
Irritable bowel syndrome (IBS) is a common health issue that is
characterized by abdominal pain, abnormal bowel movements, and altered visceral
perception. The complexity and variability in symptoms pose serious challenges
in treating IBS. Current therapy for IBS is primarily focused on reducing the
abdominal pain, thereby improving the quality of life to a significant extent.
Although the use of fiber rich diet is widely recommended in treating IBS, some
studies have questioned its use. Intra-colonic butyrate, a short-chain fatty
acid, is primarily produced by the fermentation of dietary fibers in the colon.
In the existing literature there are conflicting reports about the function of
butyrate. In rats it is known to induce visceral hypersensitivity without
altered pathology, whereas in humans it has been reported to reduce visceral
pain. Understanding the molecular mechanisms responsible for this contrasting
effect of butyrate is important before recommending fiber rich diet to IBS
patients.
Considering this report it is possible that butyrate at physiologically
relevant concentrations might be effective in decreasing the colonic
hypersensitivity whereas a higher concentration might produce an opposite
effect.
Further studies in this direction are required to obtain conclusive
evidence before undertaking clinical trials for the treatment of visceral pain
in IBS patients.
Pain. 2002
Nov;100(1-2):91-7.
Short-chain fatty
acid enemas fail to decrease colonic hypersensitivity and inflammation in
TNBS-induced colonic inflammation in rats.
Tarrerias AL1, Millecamps M, Alloui A, Beaughard C, Kemeny JL, Bourdu S, Bommelaer G, Eschalier A, Dapoigny M, Ardid D.
·
1Service
de Gastro-Entérologie, Hotel-Dieu, 63000 Clermont-Ferrand, France.
Abstract
BACKGROUND AND
AIMS:
Short-chain fatty acid (SCFA) (especially butyrate) enemas are
widely used to reduce symptoms associated with human inflammatory bowel
disease. The purpose of this study was to evaluate their real effect on colonic
sensitivity in rats.
METHODS:
The effects of saline and SCFA enemas (acetate, propionate and
particularly butyrate) were studied on visceral pain thresholds following
colonic distension in control rats and in rats with colitis (instilled with
trinitrobenzene sulfonic acid (TNBS)).
RESULTS:
Butyrate enemas (40 mM twice daily for 14 days) decreased colonic
pain thresholds in control rats; they did not reduce the TNBS-induced
hypersensitivity, but on the contrary increased its duration (without modifying
the inflammation score). This pronociceptive effect was confirmed in control
rats receiving twice daily enemas of 80 mM for 3 days and two enemas of 240 mM
of a butyrate solution. The other SCFA enemas did not modify the
hypersensitivity of rats with colitis and induced proinflammatory effects.
CONCLUSIONS:
The beneficial effect of SCFA (especially butyrate) enemas on
hypersensitivity and inflammation in inflammatory bowel disease is questionable
and needs to be thoroughly investigated in humans.
Gastroenterology. 2005
Jun;128(7):1996-2008.
Rectal
instillation of butyrate provides a novel clinically relevant model of
noninflammatory colonic hypersensitivity in rats.
Bourdu S1, Dapoigny M, Chapuy E, Artigue F, Vasson MP, Dechelotte P, Bommelaer G, Eschalier A, Ardid D.
·
1Laboratoire
de Pharmacologie Médicale, Faculté de Médecine, Clermont-Ferrand, France.
Abstract
BACKGROUND &
AIMS:
The treatment of irritable bowel syndrome (IBS), characterized by
abdominal pain and bloating, is empirical and often poorly efficient. Research
lacks suitable models for studying the pathophysiologic mechanisms of the
colonic hypersensitivity and new pharmacologic targets. The present study aimed
to develop a novel model of colonic hypersensitivity possessing several of the
characteristics encountered in patients with IBS.
METHODS:
Rats received enemas of a butyrate solution (8-1000 mmol/L) twice
daily for 3 days. A time course was determined for colonic hypersensitivity
(colorectal distention test) and referred cutaneous lumbar hyperalgesia (von
Frey hairs). Macroscopic and histologic analyses were performed on colonic
mucosa. The efficacy of morphine, U50488H (a kappa opioid agonist), and
trimebutine on the 2 pain parameters was determined. Finally, the involvement
of peptidergic C-fibers was evaluated using capsaicin-pretreated animals and
treatments with calcitonin gene-related peptide (CGRP) and neurokinin 1
receptor antagonists.
RESULTS:
Butyrate enemas induced a sustained, concentration-dependent
colonic hypersensitivity and, to a lesser extent, a referred cutaneous
mechanical hyperalgesia, particularly in female rats, but no macroscopic and
histologic modifications of the colonic mucosa, as observed in patients with
IBS. Both pain parameters were sensitive to morphine, U50488H, trimebutine,
neonatal capsaicin treatment, and the CGRP receptor antagonist but not to the
neurokinin 1 receptor antagonist.
CONCLUSIONS:
These results present our noninflammatory model of chronic colonic
hypersensitivity as a useful novel tool for studying IBS. The CGRP receptor
antagonist-induced reduction of colonic hypersensitivity suggests that CGRP
receptors may provide a promising target for treatment of IBS.
・・・・・・・・・・・・・・・・・・・・
2016年7月14日
短鎖脂肪酸：プロピオン酸増加はIBSに関係する。
乳糖やオリゴ糖などの高FODMAP食は、腸内で発酵して、腸内でガスや水分を増加させ、それによりIBS症状を来します。
しかし、それだけでIBS症状を来すことに疑問があります。
同じ高FODMAP食でも、人によって症状が違うことがあります。
腸管内で症状を悪化させる何らかの機序が存在するという前提で、
それをブラックボックスと表現しました。
高FODMAP食による発酵で、増加するのはガスや水分だけでなく、短鎖脂肪酸があります。
この短鎖脂肪酸には酢酸、プロピオン酸、酪酸、イソ吉草酸などの種類がありますが、これらは総じて善玉物質と考えられていましたが、最近では、それらは個々において異なった作用を来すことがわかってきました。
食物繊維にはセルロース、ヘミセルロースがありますが、セルロース分解菌で発酵し、プロピオン酸を産生します。
そして、プロピオン酸相対的増加とIBS症状と密接な関係があることがわかってきました。
http://www.ncbi.nlm.nih.gov/pubmed/27121286
BMC Gastroenterol. 2016
Apr 27;16(1):51. doi: 10.1186/s12876-016-0446-z.
Faecal short-chain fatty acids
- a diagnostic biomarker for irritable bowel syndrome?
Farup PG1,2, Rudi K3, Hestad K4,5,6.
·
1Department of Research, Innlandet Hospital Trust,
N-2381, Brumunddal, Norway. per.farup@ntnu.no.
·
2Unit for Applied Clinical Research, Department of
Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian
University of Science and Technology, N-7491, Trondheim, Norway.
per.farup@ntnu.no.
·
3Department of Chemistry, Biotechnology and Food Science,
Norwegian University of Life Sciences, P.O. Box 5003, , N-1432, Ås, Norway.
·
4Department of Research, Innlandet Hospital Trust,
N-2381, Brumunddal, Norway.
·
5Department of Psychology, Faculty of Social Sciences
and Technology Management, Norwegian University of Science and Technology,
N-7491, Trondheim, Norway.
·
6Department of Public Health, Hedmark University
College, N-2418, Elverum, Norway.
Abstract
BACKGROUND:
The diagnosis of irritable
bowel syndrome (IBS) relies on symptom-based criteria. A valid and
reliable biomarker that could confirm the diagnosis is desirable. This study
evaluated the properties of faecal short-chain fatty acids (SCFA) as diagnostic
biomarkers for IBS.
METHODS:
Twenty-five subjects with IBS
and 25 controls were included in this explanatory case-control study. Stool
samples were analysed forSCFA (acetic acid, propionic acid, butyric acid,
isobutyric acid, valeric acid, and isovaleric acid) with gas chromatography and
reported as mmol/l and molar%. In the search for the best way to distinguish
between subjects with and without IBS, the total amount and the amount of each
of theSCFA were measured, and the proportions and differences between the SCFA were
calculated.
RESULTS:
In the IBS and control group,
the mean age was 46.2 (SD 12.9) and 49.2 (SD 14.6), and the number of females
was 13/25 (52 %) and 15/25 (60 %) respectively. The difference
between propionic and butyric acid (mmol/l) had the best diagnostic properties,
the area under the Receiver Operating Characteristic curve was 0.89 (95 %
CI: 0.80-0.98) (p < 0.001). With a cut-off value > 0.015 mmol/l
indicating IBS, the sensitivity, specificity, positive and negative likelihood
ratio, and diagnostic odds ratio were 92 %, 72 %, 3.29, 0.11 and 29.6
respectively. Similar diagnostic properties were shown for all the IBS
subgroups.
CONCLUSIONS:
The study indicated that faecal SCFA could
be a non-invasive, valid and reliable biomarker for the differentiation of
healthy subjects from subjects with IBS.
・・・・・・・・・・・・・・・・・・・・・・・・・・・・
また、東北大学の研究では、高濃度の酢酸とプロピオン酸は、IBSの腹部症状と感情を悪化させることもわかっています。
以上から、これまで、判明していることをまとまると、以下になります。
＜関連文献＞
短鎖脂肪酸はその種類によって遠位、近位の結腸に異なる作用を来す。
Neurogastroenterol Motil. 2014
Nov;26(11):1586-96. doi: 10.1111/nmo.12425. Epub 2014 Sep 16.
The short chain fatty acids,
butyrate and propionate, have differential effects on the motility of the
guinea pig colon.
Hurst NR1, Kendig DM, Murthy KS, Grider JR.
·
1Department of Physiology and Biophysics, VCU Program in
Enteric Neuromuscular Science (VPENS), Virginia Commonwealth University,
Richmond, VA, USA.
Erratum in
·
Erratum. [Neurogastroenterol Motil. 2015]
Abstract
BACKGROUND:
Colonic microbiota digest
resistant starches producing short chain fatty acids (SCFAs). The main SCFAs
produced are acetate, propionate, and butyrate. Both excitatory and inhibitory
effects of SCFAs on motility have been reported. We hypothesized that the
effect of SCFAs on colonic motility varies with chain length and aimed to
determine the effects of SCFAs on propagating and non-propagating contractions
of guinea pig proximal and distal colon.
METHODS:
In isolated proximal colonic
segments, Krebs solution alone or containing 10-100 mM acetate, propionate, or
butyrate was injected into the lumen, motility was videorecorded over 10 min,
and spatiotemporal maps created. In distalcolon, the lumen was perfused with
the same solutions of SCFAs at 0.1 mL/min, the movement of artificial fecal
pellets videorecorded, and velocity of propulsion calculated.
KEY RESULTS:
In proximal colon,
butyrate increased the frequency of full-length propagations, decreased short propagations,
and had a biphasic effect on non-propagating contractions. Propionate blocked
full and short propagations and had a biphasic effect on non-propagating
contractions. Acetate decreased short and total propagations. In distal colon,
butyrate increased and propionate decreased velocity of propulsion.
CONCLUSIONS & INFERENCES:
The data suggest that luminal
SCFAs have differing effects on proximal and distal colonic motility depending
on chain length. Thus,
the net effect of SCFAs on colonic motility would depend on the balance of
SCFAs produced by microbial digestion of resistant starches.
東北大：高濃度の酢酸とプロピオン酸は腹部症状と負の感情に相関する。
Neurogastroenterol Motil. 2010
May;22(5):512-9, e114-5. doi: 10.1111/j.1365-2982.2009.01427.x. Epub 2009 Nov
10.
Altered profiles of intestinal
microbiota and organic acids may be the origin of symptoms inirritable bowel
syndrome.
Tana C1, Umesaki Y, Imaoka A, Handa T, Kanazawa M, Fukudo S.
·
1Department of Behavioral Medicine, Tohoku University
Graduate School of Medicine, Sendai, Japan.
Abstract
BACKGROUND:
The profile of intestinal
organic acids in irritable bowel syndrome (IBS) and its correlation
with gastrointestinal (GI) symptoms are not clear. We hypothesized in this
study that altered GI microbiota contribute to IBS symptoms through increased
levels of organic acids.
METHODS:
Subjects were 26 IBS patients
and 26 age- and sex-matched controls. Fecal samples were collected for
microbiota analysis using quantitative real-time polymerase chain reaction and
culture methods, and the determination of organic acid levels using
high-performance liquid chromatography. Abdominal gas was quantified by image
analyses of abdominal X-ray films. Subjects completed a questionnaire for GI
symptoms, quality of life (QOL) and negative emotion.
KEY RESULTS:
Irritable bowel syndrome patients
showed significantly higher counts of Veillonella (P = 0.046) and Lactobacillus
(P = 0.031) than controls. They also expressed significantly higher levels of
acetic acid (P = 0.049), propionic acid (P = 0.025) and total organic acids (P
= 0.014) than controls. The quantity of bowel gas was not
significantly different between controls and IBS patients. Finally, IBS
patients with high acetic acid or propionic acid levels presented with
significantly worse GI symptoms, QOL and negative emotions than those with low
acetic acid or propionic acid levels or controls.
CONCLUSIONS & INFERENCES:
These results support the
hypothesis that both fecal microbiota and organic acids are altered in IBS
patients. A combination of Veillonella and Lactobacillus is known to produce
acetic and propionic acid. High levels of acetic and propionic acid may associate
with abdominal symptoms, impaired QOL and negative emotions in IBS.
Am
J Gastroenterol. 2015 Sep;110(9):1339-46. doi:
10.1038/ajg.2015.220. Epub 2015 Aug 25.
http://www.ncbi.nlm.nih.gov/pubmed/26303129
Altered Colonic Bacterial
Fermentation as a Potential Pathophysiological Factor in Irritable Bowel
Syndrome.
Ringel-Kulka T1, Choi CH2,3, Temas D2, Kim A1,4, Maier DM2, Scott K5, Galanko JA2, Ringel Y2.
Abstract
OBJECTIVES:
Dysbiosis leading to abnormal
intestinal fermentation has been suggested as a possible etiological mechanism
in irritable bowel syndrome (IBS). We aimed to investigate the
location and magnitude of altered intestinal bacterial fermentation in IBS and
its clinical subtypes.
METHODS:
IBS patients who satisfied the
Rome III criteria (114) and 33 healthy controls (HC) were investigated.
Intestinal fermentation was assessed using two surrogate measures: intestinal
intraluminal pH and fecal short-chain fatty acids (SCFAs). Intraluminal pH and
intestinal transit times were measured in the small and large bowel using
a wireless motility capsule (SmartPill) in 47 IBS and 10 HC. Fecal SCFAs
including acetate, propionate, butyrate, and lactate were analyzed by capillary
gas chromatography in all enrolled subjects. Correlations between intestinal
pH, fecal SCFAs, intestinal transit time, and IBS symptom scores were analyzed.
RESULTS:
Colonic intraluminal pH levels
were significantly lower in IBS patients compared with HC (total colonic pH,
6.8 for IBS vs. 7.3 for HC, P=0.042). There were no differences in total and
segmental pH levels in the small bowel between IBS patients and HC
(6.8 vs. 6.8, P=not significant). The intraluminal colonic pH differences were
consistent in all IBS subtypes. Total SCFA level was significantly
lower in C-IBS patients than in D-IBS and M-IBS patients and HC. The totalSCFA level
in all IBS subjects was similar with that of HC. Colonic pH levels correlated
positively with colon transit time (CTT) and IBS symptoms severity.
Total fecal SCFAs levels correlated negatively with CTT and
positively with stool frequency.
CONCLUSIONS:
Colonic intraluminal pH is
decreased, suggesting higher colonic fermentation, in IBS patients compared
with HC. Fecal SCFAs are not a sensitive marker to estimate intraluminal
bacterial fermentation.
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