Small Intestinal Bacterial Overgrowth (SIBO)

The definition of Small Intestinal Bacterial Overgrowth (SBIO) is the presence of bacterial overgrowth in the small intestine.

The healthy small bowel has less bacterial colonization compared with the colon. However, in some conditions or diseases, bacterial overgrowth in the small intestine causes gastrointestinal symptoms, such as pain, bloating, cramps, diarrhea and constipation. This can be observed in diseases such as post-abdominal surgery, inflammatory bowel disease especially Chhorn’s disease, celiac disease, cirrhosis and motility disorders. Recently, according with the increasing knowledge of the gut microbiome and its roles in human health, SIBO has gotten attention in relation with irritable bowel syndrome (IBS).

Diagnosis of SIBO

Since SIBO is defined by the presence of excessive numbers of bacteria within the small intestine, the classical diagnostic method was quantitative culture of aspirates acquired from the proximal small bowel through upper endoscopy. Recently, several studies assessed SBIO by 16S ribosomal RNA gene sequencing. With this technique, IBS patients are shown to have less microbial diversity and overgrowth of certain species. Although the aspiration of intestinal contents by endoscopy is direct and objective, the utility is still limited due to the lack of standardized technique and validation of the cutoff value. It is also invasive and can only evaluate the proximal part of the small intestine.

Breath Test

Human cells do not produce hydrogen and methane gases. If these gases are detected in breath samples, they are produced by gut microbiome through fermentation of carbohydrates. For the standardized evaluation, patients have to avoid taking antibiotics for 4 weeks, laxatives for 1 week and fermentable foods for 1 day, and should fast for 8-12 hours before examination. After ingestion of sugar, it is rapidly fermented to produce hydrogen gas, and methanogenic archaea further produce methane gas from hydrogen. Substrates are either 75g glucose or 10g lactulose, in which glucose may reflect only the proximal part of intestine due to early absorption, while lactulose shows 2 peaks, in which the second peak may reflect colonic bacterial fermentation. Likewise, the level of methane on breath test may reflect both the small intestine and colon. Increased methane is shown to associate with slowing gut motility and causing constipation. The sensitivity and specificity of the breath tests have shown to be both 40-80%.

Treatment of SIBO

Several antibiotics such as amoxicillin-clavulanic acid, ciprofloxacin, metronidazole, trimethoprim-sulfamethoxazole have been studied, although adverse effects especially pseudomembranous colitis due to an overgrowth of Clothtridioides difficile have to be watched out. Rifaximin has recently been shown to improve abdominal symptoms in IBS patients with reduction in methane on repeat breath test. Although SIBO frequently recurs following a course of antibiotic therapy, the optimal treatment period and protocol has yet to be determined.

Either low FODMAP (fermentable oligo-, di-, mono-saccharides and polyols) diet or use of probiotics has been shown to be effective on either improvement in clinical symptoms or gas pattern on breath testing, though the evidence grade is low. The effect of fecal microbiota transplant has also remained to be determined.

Effect of PPI

Gastric acid plays an important role in preventing bacterial overgrowth in the upper GI tract. Proton-pump inhibitors (PPI), potent inhibitors for gastric acid production, are among the most common medications treating acid-reflux and related symptoms/diseases. It is likely that PPI may cause SIBO, however, a recent meta-analysis concluded that the dose, duration, and type of PPI are not associated with the risk of developing SIBO. It is also shown to have no effect on the result of methane breath test, as well as microbial diversity in sequencing.

小腸内細菌異常増殖(SIBO)

小腸内細菌異常増殖(SBIO)の定義は、小腸内の細菌異常増殖の存在です。 健康な小腸は、結腸に比べて細菌のコロニー形成が少ないです。 ただし、一部の状態や病気では、小腸の細菌異常増殖により、痛み、腹部膨満、けいれん、下痢、便秘などの胃腸症状が引き起こされます。 これは、腹部手術後、炎症性腸疾患、特にChhorn病、セリアック病、肝硬変、運動障害などの疾患で観察されます。 最近、腸内細菌叢と人間の健康におけるその役割についての知識の増加に伴い、SIBOは過敏性腸症候群(IBS)に関連して注目を集めています。

SIBOの診断

SIBOは小腸内に過剰な数の細菌が存在することで定義されるため、古典的な診断方法は、上部内視鏡検査によって近位小腸から採取した吸引物の定量培養でした。最近、いくつかの研究が16SリボソームRNA遺伝子配列決定によってSBIOを評価しました。この技術により、IBS患者は特定の種の微生物の多様性と異常増殖が少ないことが示されています。内視鏡検査による腸内容物の吸引は直接的かつ客観的ですが、標準化された技術とカットオフ値の検証が不足しているため、有用性は依然として制限されています。また、侵襲性があり、小腸の近位部分しか評価できません。

呼気検査

人間の細胞は水素とメタンガスを生成しません。これらのガスが呼気サンプルで検出された場合、それらは炭水化物の発酵を通じて腸内細菌叢によって生成されます。標準化された評価では、患者は抗生物質を4週間、下剤を1週間、発酵性食品を1日間服用することを避け、検査前に8〜12時間絶食する必要があります。砂糖を摂取した後、急速に発酵して水素ガスを生成し、メタン生成古細菌はさらに水素からメタンガスを生成します。基質は75gのグルコースまたは10gのラクツロースであり、グルコースは早期吸収のために腸の近位部分のみを反映する可能性があり、ラクツロースは2つのピークを示し、2番目のピークは結腸の細菌発酵を反映する可能性があります。同様に、呼気検査でのメタンのレベルは、小腸と結腸の両方を反映している可能性があります。メタンの増加は、腸の運動を遅くし、便秘を引き起こすことに関連していることが示されています。呼気検査の感度と特異性は両方とも40-80%であることが示されています。

SIBOの治療

アモキシシリン-クラブラン酸、シプロフロキサシン、メトロニダゾール、トリメトプリム-スルファメトキサゾールなどのいくつかの抗生物質が研究されていますが、特にクロストリジウム・ディフィシルの異常増殖による偽膜性大腸炎への悪影響に注意する必要があります。 リファキシミンは最近、反復呼気検査でメタンが減少し、IBS患者の腹部症状を改善することが示されました。 SIBOは抗生物質療法の経過後に頻繁に再発しますが、最適な治療期間とプロトコルはまだ決定されていません。

エビデンスグレードは低いものの、低FODMAP(発酵性オリゴ糖、二糖、単糖、およびポリオール)食またはプロバイオティクスの使用は、臨床症状または呼気検査のガスパターンの改善に効果的であることが示されています。 糞便微生物移植の効果もまだ決定されていません。

PPIの効果

胃酸は、上部消化管での細菌の異常増殖を防ぐのに重要な役割を果たします。 胃酸産生の強力な阻害剤であるプロトンポンプ阻害剤(PPI)は、胃酸逆流症および関連する症状/疾患を治療する最も一般的な薬剤の1つです。 PPIはSIBOを引き起こす可能性がありますが、最近のメタアナリシスでは、PPIの用量、期間、および種類はSIBOを発症するリスクとは関連がないと結論付けています。 また、メタン呼気検査の結果、およびシーケンスにおける微生物の多様性にも影響を与えないことが示されています。

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