BACKGROUND & AIMS Irritable bowel syndrome (IBS) is characterized by abdominal pain, bloating, and erratic bowel habits. A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) can reduce symptoms of IBS, possibly by reducing microbial fermentation products. We investigated whether ingestion of FODMAPs can induce IBS-like visceral hypersensitivity mediated by fermentation products of intestinal microbes in mice. METHODS C57Bl/6 mice were gavaged with lactose, with or without the antiglycation agent pyridoxamine, or saline (controls) daily for 3 weeks. A separate group of mice were fed a diet containing fructo-oligosaccharides, with or without pyridoxamine in drinking water, or a normal chow diet (controls) for 6 weeks. Feces were collected and analyzed by 16S ribosomal RNA gene sequencing and bacterial community analyses. Abdominal sensitivity was measured by electromyography and mechanical von Frey filament assays. Colon tissues were collected from some mice and analyzed by histology and immunofluorescence to quantify mast cells and expression of advanced glycosylation end-product specific receptor (AGER). RESULTS Mice gavaged with lactose or fed fructo-oligosaccharides had increased abdominal sensitivity compared with controls, associated with increased numbers of mast cells in colon and expression of the receptor for AGER in proximal colon epithelium. These effects were prevented by administration of pyridoxamine. Lactose and/or pyridoxamine did not induce significant alterations in the composition of the fecal microbiota. Mass spectrometric analysis of carbonyl compounds in fecal samples identified signatures associated with mice given lactose or fructo-oligosaccharides vs controls. CONCLUSIONS We found that oral administration of lactose or fructo-oligosaccharides to mice increases abdominal sensitivity, associated with increased numbers of mast cells in colon and expression of AGER; these can be prevented with an antiglycation agent. Lactose and/or pyridoxamine did not produce alterations in fecal microbiota of mice. Our findings indicate that preventing glycation reactions might reduce abdominal pain in patients with IBS with sensitivity to FODMAPs.

中文翻译：

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乳糖和低聚果糖通过糖基化过程增加小鼠的内脏敏感性，从而增加结肠粘膜的肥大细胞密度。

背景与目的肠易激综合症（IBS）的特征是腹痛，腹胀和肠蠕动不规律。少摄入可发酵的低聚糖，二糖，单糖和多元醇（FODMAP）的饮食可以减轻IBS的症状，这可能是通过减少微生物发酵产物来实现的。我们调查了摄取FODMAPs是否可以诱导小鼠肠道微生物发酵产物介导的IBS样内脏超敏反应。方法每天给C57Bl / 6小鼠喂食乳糖，加或不加抗糖化剂吡ido胺或生理盐水（对照组），持续3周。另一组小鼠被喂食含有果糖低聚糖的饮食，饮用水中有或没有吡ido胺，或正常的饮食（对照组），为期6周。收集粪便并通过16S核糖体RNA基因测序和细菌群落分析进行分析。通过肌电图和机械冯弗雷丝测定法测量腹部敏感性。从一些小鼠收集结肠组织，并通过组织学和免疫荧光分析以定量肥大细胞和晚期糖基化终产物特异性受体（AGER）的表达。结果与对照组相比，饲喂乳糖或低聚果糖的小鼠腹部敏感性更高，这与结肠肥大细胞数量增加以及近端结肠上皮中AGER受体的表达有关。通过施用吡ido胺可以防止这些作用。乳糖和/或吡ido胺未引起粪便微生物群组成的显着改变。粪便样品中羰基化合物的质谱分析确定了与给予乳糖或低聚果糖的小鼠相对于对照组相关的特征。结论我们发现，对小鼠口服乳糖或低聚果糖可增加腹部敏感性，这与结肠中肥大细胞数量的增加和AGER的表达有关。这些可以用抗糖化剂预防。乳糖和/或吡ido胺未在小鼠的粪便微生物区系中产生改变。我们的发现表明，预防糖基化反应可以减轻对FODMAPs敏感的IBS患者的腹痛。结论我们发现，对小鼠口服乳糖或低聚果糖可增加腹部敏感性，这与结肠中肥大细胞数量的增加和AGER的表达有关。这些可以用抗糖化剂预防。乳糖和/或吡ido胺未在小鼠的粪便微生物区系中产生改变。我们的发现表明，预防糖基化反应可以减轻对FODMAPs敏感的IBS患者的腹痛。结论我们发现，对小鼠口服乳糖或低聚果糖可增加腹部敏感性，这与结肠中肥大细胞数量的增加和AGER的表达有关。这些可以用抗糖化剂预防。乳糖和/或吡ido胺未在小鼠的粪便微生物区系中产生改变。我们的发现表明，预防糖基化反应可以减轻对FODMAPs敏感的IBS患者的腹痛。