The Effect of the Gluten-Free Diet on the Metabolic Activity of the Intestinal Microbiota in Patients with Celiac Disease

S. Bykova, E. Sabelnikova, S. Silvestrova, T. Kuzmina, E. Baulo, A. Parfenov
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Abstract

The aim is to study the effect of the gluten-free diet (GFD) on the spectrum of short-chain fatty acids (SСFAs) in the intestine in patients with celiac disease. Material and methods. 61 patients with celiac disease were examined, confirmed by positive serological tests and histological examination of the mucous membrane of the small intestine. Men were 17 (13.7%), median age – 41 years; women – 44 (86.3%), median age – 45 years. The first group included patients with newly diagnosed celiac disease (n = 21); the second group included patients who observe GFD, consciously or unconsciously violate it (n = 20); the third group consisted of patients who strictly observe GFD (n = 20). The duration of dietary treatment of patients of the second group ranged from two hundred months to seven years, in patients of the third group – from one year to eight years.The level of SСFAs in feces was determined by gas-liquid chromatography on the Crystal 2000 M chromatograph. The control group consisted of 22 healthy volunteers, among them were 6 (27.3%) men, 16 (72.7%) women, the median age was 42 years (Q1-Q3: 32–58 years; Shapiro p-value < 0.01). Statistical analysis was performed using parametric and nonparametric methods according to the Statistica 13.3 program (StatSoft Inc., USA). Results. The total level of SCFAs in the coprofiltrate of patients of the first group was slightly higher than in the control group (13.15 ± 1.52 vs 9.8 ± 2.1 mg/g; p = 0.278), the anaerobic index was significantly higher (1.43 ± 0.23 vs 0.754 ± 0.15 mg/g; p = 0.017), which indicated an increase in the metabolic activity of anaerobic bacteria. Significant differences in patients of the first group and in the control group were obtained in the levels of propionic acid (3.85 ± 0.62 vs 1.65 ± 0.46 mg/g; p = 0.006); isobutyric acid (0.67 ± 0.1 vs 0.28 ± 0.1 mg/g; p = 0.009) and valerian acid (0.83 ± 0.13 vs 0.32 ± 0.09 mg/g; p = 0.002). In patients of the second group, a significant decrease in the total amount of SCFAs was found compared with the control group (4.6 ± 0.9 vs 9.8 ± 2.1 mg/g; p = 0.034). Also, in the second group, compared with the control group, a significant decrease in the concentration of acetic acid was revealed (1.9 ± 1.2 vs 5.36 ± 1.1 mg/g; p = 0.045). The level of isovaleric acid was increased in the second group compared to the third group (0.66 ± 0.14 vs 0.22 ± 0.13 mg/g; p = 0.04), and the level of capronic acid concentration was reduced (0.05 ± 0.1 vs 0.35 ± 0.1 mg/g; p = 0.04). These data indirectly indicated a decrease in the number of representatives of the saccharolytic microflora in the second group. Conclusion. When studying the spectrum and concentration of SCFAs in the feces of patients with celiac disease who are at different stages of treatment of GFD and recovery of MMSI, there is a tendency to multidirectional metabolic activity of the colonic microbiota. As the GFD is observed, the overall level of SCFAs decreases, there is a shift in the ratio of anaerobes and aerobic bacteria, the level of isovaleric acid increases and the tendency to increase isobutyric acid decreases, the level of acetic and caproic acids decreases. To optimize the treatment of patients with celiac disease, further monitoring of the metabolic activity of the intestinal microbiota in the process of dynamic observation is required.
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无麸质饮食对乳糜泻患者肠道菌群代谢活性的影响
目的是研究无麸质饮食(GFD)对乳糜泻患者肠道短链脂肪酸谱(SСFAs)的影响。材料和方法。对61例乳糜泻患者进行了检查,经血清学试验和小肠粘膜组织学检查阳性证实。男性17岁(13.7%),中位年龄41岁;女性44岁(86.3%),中位年龄45岁。第一组包括新诊断为乳糜泻的患者(n = 21);第二组包括自觉或不自觉违反GFD的患者(n = 20);第三组为严格遵守GFD的患者(n = 20)。第二组患者的饮食治疗时间从200个月到7年不等,第三组患者的饮食治疗时间从1年到8年不等。采用Crystal 2000m色谱仪气液色谱法测定粪便中SСFAs的含量。对照组22例健康志愿者,其中男性6例(27.3%),女性16例(72.7%),中位年龄42岁(Q1-Q3: 32-58岁;Shapiro p值< 0.01)。根据Statistica 13.3程序(StatSoft Inc., USA),采用参数和非参数方法进行统计分析。结果。第一组患者共廓中SCFAs总水平略高于对照组(13.15±1.52 vs 9.8±2.1 mg/g;P = 0.278),厌氧指数显著高于对照组(1.43±0.23 vs 0.754±0.15 mg/g;P = 0.017),说明厌氧菌的代谢活性增加。第一组患者丙酸水平与对照组有显著差异(3.85±0.62 vs 1.65±0.46 mg/g;P = 0.006);异丁酸(0.67±0.1 vs 0.28±0.1 mg/g;P = 0.009)和缬草酸(0.83±0.13 vs 0.32±0.09 mg/g;P = 0.002)。在第二组患者中,与对照组相比,scfa总量显著降低(4.6±0.9 vs 9.8±2.1 mg/g;P = 0.034)。此外,与对照组相比,第二组的乙酸浓度显著降低(1.9±1.2 vs 5.36±1.1 mg/g);P = 0.045)。与第三组相比,第二组的异戊酸水平升高(0.66±0.14 vs 0.22±0.13 mg/g;P = 0.04),己酸浓度水平降低(0.05±0.1 vs 0.35±0.1 mg/g;P = 0.04)。这些数据间接表明第二组中糖溶菌群的代表数量有所减少。结论。在研究处于GFD治疗和MMSI恢复不同阶段的乳糜泻患者粪便中SCFAs的谱和浓度时,发现结肠微生物群有多向代谢活动的趋势。随着GFD的观察,SCFAs总体水平降低,厌氧菌与好氧菌的比例发生变化,异戊酸水平升高,异丁酸升高的趋势减弱,乙酸和己酸水平降低。为了优化乳糜泻患者的治疗,需要进一步监测肠道菌群在动态观察过程中的代谢活性。
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