Intestinal barrier (IB) dysfunction plays a role in pathogenesis of intestinal diseases including irritable bowel syndrome (IBS) with bile acid diarrhoea (BAD).¹ Dietary nutrients or supplements including whole grains may enhance IB functions by restoring the gut microbiome, mucus layer thickness,² and effects on tryptophan and short chain fatty acids (SCFA).^{3, 4} Hemp seeds provide all essential amino acids, polyunsaturated fats, fibre, minerals and vitamins.⁵ Hemp hulls are also rich in bioactive phenolics, which enhance gut barrier function in vitro.⁶ Bio gut fibre (BGF) is a minimally processed fibre ingredient from hemp hulls and is generally recognized as safe (GRAS status, U.S. FDA 2021a). We hypothesized that BGF reduces intestinal permeability in BAD.

In a pilot, single-arm, open-label, prospective study, 10 participants with a prior biochemical diagnosis of BAD (based on serum [n = 8] or stool [n = 2]) associated with IBS consumed 10 g BGF twice daily for 3 weeks, delivering 15 g of insoluble dietary fibre. At baseline and end of treatment, they underwent measurements of small intestinal (SI) and colonic permeability (IP)⁷ using oral 100 mg ¹³C-mannitol (estimated molecular diameter [EMD] 6.7 Å) and 1 g lactulose (EMD 9.5 Å), based on sugars' excretion at 0–2 h (reflecting upper small bowel), 2–8 h (SI and proximal colon) and 0–24 h (total gut permeability).^{7, 8} The study was powered to detect a 0–24 h difference of 5.5 mg ¹³C-mannitol excretion between baseline and treatment, based on coefficient of variation in BAD.¹

During each 24 h study, participants ingested three standardized meals. Bile acid sequestrants were withheld 2 weeks prior to initiation and throughout the study. The primary endpoints were ¹³C-mannitol excretion during 2–24 h (SI and colonic permeability) and 0–24 h (whole gut permeability). Mass of sugars excreted is more sensitive than lactulose: mannitol ratio for detecting alterations in permeability.² Statistical analysis compared baseline and end of treatment excretions (paired t-test). A post hoc analysis evaluated five patients with baseline ¹³C-mannitol excretion >10 mg in the 2–24 h collection.

Among 10 participants (nine female), mean age was 48.2 (SD ±12.91) years and BMI 30.87 (SD ±6.91) kg/m². There were no significant differences in the two sugar excretion profiles in the individual or combined urine collections: 0–24 h ¹³C-mannitol excretions were 22.2 ± 6[SEM]mg at baseline and 17.0 ± 3.6 mg at end of study; 0–24 h lactulose excretions were 3.5 ± 0.8 mg and 3.8 ± 1.1 mg, respectively. Post hoc analysis in patients with baseline 0–24 h ¹³C-mannitol excretion ≥10 mg showed numerically reduced ¹³C-mannitol excretion with treatment in both 2–24 h and 0–24 h measurements (Figure 1).

Thus, BGF reduces intestinal permeability to ¹³C-mannitol in patients with IBS-BAD with ≥10 mg excretion at baseline, consistent with reduced pore rather than leak pathway permeability (given lack of effect on lactulose excretion).⁹ Hemp hull bioactives, such as HNF4α agonists, NCT (N-trans-caffeoyl tyramine) and NFT (N-trans-feruloyl tyramine), may also affect gut barrier by reducing permeability in human colon primary cell culture, among other beneficial properties.⁵

In conclusion, hemp hull may be beneficial to restore IB integrity in patients with higher levels of increased mucosal permeability (>10 mg ¹³C-mannitol excretion) at baseline. Further studies are warranted in diseases with increased intestinal permeability, including coeliac disease, Crohn's disease and ulcerative colitis.¹⁰

肠屏障（IB）功能障碍在肠道疾病的发病机制中发挥着重要作用，包括肠易激综合征（IBS）伴胆汁酸腹泻（BAD）。 ¹ 膳食营养素或补充剂（包括全谷物）可以通过恢复肠道微生物群、粘液层厚度、 ² 以及对色氨酸和短链脂肪酸 (SCFA) 的影响来增强 IB 功能。 ^{3, 4} 大麻籽提供所有必需氨基酸、多不饱和脂肪、纤维、矿物质和维生素。 ⁵ 大麻皮还富含生物活性酚类物质，可增强体外肠道屏障功能。 ⁶ 生物肠纤维 (BGF) 是一种从大麻壳中提取的经过最低限度加工的纤维成分，通常被认为是安全的（GRAS 状态，美国 FDA 2021a）。我们假设 BGF 会降低 BAD 中的肠道通透性。

在一项单臂、开放标签、前瞻性研究中，10 名先前生化诊断为与 IBS 相关的 BAD（基于血清 [n = 8] 或粪便 [n = 2]）的参与者每天服用两次 10 g BGF持续 3 周，提供 15 克不溶性膳食纤维。在基线和治疗结束时，他们使用口服 100 mg ¹³ C-甘露醇（估计分子直径 [EMD]）测量小肠 (SI) 和结肠渗透性 (IP) ⁷ 6.7 Å) 和 1 g 乳果糖 (EMD 9.5 Å)，基于 0–2 小时（反映小肠上部）、2–8 小时（SI 和近端结肠）和 0–24 小时（总肠道通透性）的糖排泄。 ^{7, 8} 该研究基于 BAD 变异系数，检测基线和治疗之间 0-24 小时 5.5 mg ¹³ C-甘露醇排泄的差异。 ¹

在每 24 小时的研究中，参与者摄入三顿标准化膳食。在开始前两周和整个研究期间停止使用胆汁酸螯合剂。主要终点是 2-24 小时（SI 和结肠通透性）和 0-24 小时（全肠道通透性）期间 ¹³ C-甘露醇排泄。对于检测渗透性的变化，排出的糖质量比乳果糖：甘露醇比率更敏感。 ² 统计分析比较基线和治疗结束时的排泄物（配对 t 检验）。事后分析评估了 5 名在 2-24 小时收集中基线 ¹³ C-甘露醇排泄量 >10 mg 的患者。

10 名参与者（9 名女性）中，平均年龄为 48.2 (SD ±12.91) 岁，BMI 为 30.87 (SD ±6.91) kg/m ² 。单独或合并尿液收集中的两种糖排泄谱没有显着差异：0–24 小时 ¹³ C-甘露醇排泄量在基线时为 22.2 ± 6[SEM]mg，在基线时为 17.0 ± 3.6 mg。学习结束； 0-24小时乳果糖排泄量分别为3.5±0.8mg和3.8±1.1mg。对基线 0-24 小时 ¹³ C-甘露醇排泄≥10 mg 的患者进行事后分析显示，2-24 小时和 0-24 小时治疗后 ¹³ C-甘露醇排泄在数值上减少。 24 小时测量（图 1）。

因此，BGF 降低了基线时排泄量≥10 mg 的 IBS-BAD 患者肠道对 C-甘露醇的通透性，这与孔道通透性降低而非渗漏途径通透性一致（考虑到对乳果糖排泄缺乏影响）。 ⁹ 大麻壳生物活性物质，如 HNF4α 激动剂、NCT（N-反式咖啡酰酪胺）和 NFT（N-反式阿魏酰酪胺），也可能通过降低人结肠原代细胞培养物的通透性来影响肠道屏障，以及其他有益的特性。 ⁵

总之，对于基线时粘膜通透性增加（>10 mg ¹³ C-甘露醇排泄）水平较高的患者，大麻壳可能有利于恢复 IB 完整性。需要对肠道通透性增加的疾病进行进一步的研究，包括乳糜泻、克罗恩病和溃疡性结肠炎。 ¹⁰