低FODMAP食の考案者であるオーストラリアのモナッシュ大ギブソン教授のグループから、ガラクトオリゴ糖食品の摂取によるIBS症状が、αガラクトシダーゼを一緒に摂取させるとIBS症状が軽快することが報告された。

Am J Gastroenterol. 2017 Aug 15. doi: 10.1038/ajg.2017.245. [Epub ahead of print]

Increasing Symptoms in Irritable Bowel Symptoms With Ingestion of Galacto-Oligosaccharides Are Mitigated by α-Galactosidase Treatment.

Tuck CJ, Taylor KM, Gibson PR, Barrett JS, Muir JG

Department Gastroenterology, Central Clinical School, Monash University and Alfred Health, Melbourne, Victoria, Australia.

Abstract

OBJECTIVES:

Galacto-oligosaccharides (GOS) are dietary FODMAPs (fermentable carbohydrates) associated with triggering gastrointestinal symptoms in patients with irritable bowel syndrome (IBS). This randomized, double-blind, placebo-controlled, cross-over trial aimed to assess whether oral α-galactosidase co-ingestion with foods high in GOS and low in other FODMAPs would reduce symptoms.

METHODS:

Patients meeting the Rome III criteria for IBS who were hydrogen-producers on breath testing were recruited. Participants were treated with full-dose (300 GALU (galactosidic units) α-galactosidase) and half-dose enzyme (150 GALU α-galactosidase), and placebo (glucose) in a random order with ≤14 days washout between arms. Following a 3-day low FODMAPrun-in period, participants consumed provided diets high in GOS for a further 3-days. Gastrointestinal symptoms were measured daily using a 100 mm visual-analogue-scale, and breath samples taken hourly on the second last day with hydrogen content analysed as area-under-the-curve.

RESULTS:

Thirty-one patients with IBS (20 IBS-D, 4 IBS-C, 7 IBS-M) completed the study. The addition of high GOS foods resulted in a significant increase in overall symptoms with 21 patients exhibiting GOS-sensitivity (>10 mm increase for overall symptoms). Of those, full-dose enzyme reduced overall symptoms (median 24. 5(IQR 17.5-35.8) vs. 5.5(1.5-15.0) mm; P=0.006) and bloating (20.5(9.5-42.0) vs. 6.5(2.0-15.8); P=0.017). Breath hydrogen production was minimal with no differences seen between placebo and full-dose (P=0.597).

CONCLUSIONS:

Oral α-galactosidase taken with high GOS foods provides a clinically significant reduction in symptoms in GOS-sensitive individuals with IBS. This strategy can be translated into practice to improve tolerance to high GOS foods as an adjunct therapy to the low FODMAP diet.Am J Gastroenterol advance online publication, 15 August 2017; doi:10.1038/ajg.2017.245.

高ガラクトオリゴ糖とともに摂取されたα-ガラクトシダーゼは、IBSに罹患したGOS感受性個体における症状の臨床的に有意な減少をもたらす。この戦略は、低FODMAP食への補助的療法として高いGOS食物に対する耐性を改善するために実践に移すことができる。

（ネット先行配信なので、論文自体はまだ公開されていない）

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論文自体の詳細はわからないが、

α-Galactosidaseは、ガラクト－ス、ガラクトース結合体（ガラクトオリゴ糖など）を分解する酵素である。

今後、このように、分解酵素の補充による低FODMAP食の長期管理の研究が行われるであろう。

αガラクトシダーゼはその欠損や低下によるFabry病が知られている。

ファブリー病（αガラクトシダーゼ欠損症）

http://grj.umin.jp/grj/fabry.htm

心疾患、腎疾患、皮膚疾患の他に、消化器症状としては下痢と腹痛があり、ファブリー病の早期症状とされ、酵素補充療法が有効とされる。

http://www.med.niigata-u.ac.jp/nephrol/achievement/research_achievement/catalog/2012/07_chosho/2012-008.pdf

ファブリー病の消化器症状の有病率は52％で、腹痛と下痢が多く、下痢型IBSと症状が類似していることがドイツから報告されている。

https://www.ncbi.nlm.nih.gov/pubmed/17919989

Clin Gastroenterol Hepatol. 2007 Dec;5(12):1447-53. Epub 2007 Oct 24.

Gastrointestinal symptoms in 342 patients with Fabry disease: prevalence and response to enzyme replacement therapy.

Hoffmann B, Schwarz M, Mehta A, Keshav S; Fabry Outcome Survey European Investigators.

Department of General Pediatrics, University Children's Hospital, Heinrich-Heine-University, Duesseldorf, Germany.

Abstract

BACKGROUND & AIMS:

Fabry disease is an X-linked deficiency of alpha-galactosidase A, resulting in lysosomal deposition of globotriaosylceramide in nearly all tissues. The disease frequently causes diarrhea and abdominal pain, which are assumed to arise from malfunction of enteric neurons and which mimic diarrhea-predominant irritable bowel syndrome (IBS). There are limited data about the prevalence and nature of gastrointestinal symptoms in patients with Fabry disease and the response to enzyme replacement therapy (ERT) in large cohorts. The aims of this study were to evaluate the nature and prevalence of gastrointestinal symptoms and their impact on health-related quality of life (HRQoL) in patients with Fabry disease and to analyze changes after 12 and 24 months of treatment with agalsidase alfa.

METHODS:

Information about gastrointestinal symptoms was obtained from regular interviews before and during the time of ERT. Data on HRQoL were collected by using the EQ-5D questionnaire.

RESULTS:

The overall prevalence of gastrointestinal symptoms was 52%, with abdominal pain and diarrhea being most frequent. Female patients were more frequently affected than male patients, and there was a high prevalence in children (abdominal pain, 49.3%; diarrhea 25.4%). ERT with agalsidase alfa reduced the prevalence of abdominal pain, with a statistically significant decrease in male patients and in children after 12 months of treatment.

CONCLUSIONS:

The gastrointestinal symptomatology of Fabry disease is very similar to diarrhea-predominant IBS; however, pathophysiologic similarities remain to be elucidated. ERT reduced the prevalence of gastrointestinal symptoms in Fabry disease, particularly in children and male patients.

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つまり、現在、下痢型IBSとされている患者のなかにも、軽症のファブリー病やファブリー病に至らないまでもαガラクトシダーゼが低下している人の存在も示唆される。
しかし、それを研究した報告はないため、まず下痢型IBS集団でのαガラクトシダーゼ測定の研究が必要である。

そして、下痢型IBS集団でのαガラクトシダーゼが正常であっても、
αガラクトシダーゼの投与が有効であるとするならば、
過剰投与になるため、過剰投与での毒性を示す必要がある。

いすれにせよ、IBSでのαガラクトシダーゼの投与の目的は、低FODMAP食療法の長期管理の一時的な補助薬というスタンスが正しいと思われる。

＜追記＞製薬メーカーにとって、IBSの巨大市場にむけて新薬開発の情報であることを認識できるか？