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Aerobic bacterial group as an early-stage biomarker from faecal samples of patients with colorectal cancer without distant metastasis. 从无远处转移的结直肠癌患者粪便样本中提取需氧菌群作为早期生物标记物。
IF 3 4区 医学 Q2 MICROBIOLOGY Pub Date : 2024-11-14 DOI: 10.1163/18762891-bja00051
D Lee, K Ahn, K Yun, Y Oh, Y S Park, Y S Kim, J-A Gim, S Mun, J-W Mun, K Han, Y J Ahn

The current approaches for detecting most colorectal polyps and early neoplasms lack sufficient sensitivity and specificity, potentially hindering treatment and ultimately reducing survival rates. Here, we performed a metagenomic analysis to identify microbiome markers in stool samples from patients with early-stage colorectal cancer (CRC). We compared the composition of gut microbiota between patients with CRC and healthy individuals, specifically focusing on patients with early-stage CRC, defined as those without core mutations (KRAS, BRAF) for CRC diagnosis, stable microsatellite instability, and distant metastasis. The aim of our study is to identify potential biomarkers from gut microbiota at different cancer stages in colorectal cancer (CRC) patients through 16S rRNA amplicon sequencing, thereby proposing a novel non-invasive method for the early diagnosis of CRC. Specific microbes were detected from groups divided based on the TNM criteria, with one group classified by tumour size only (named the T group) and another group with lymph node metastasis (named the TN group). Aerobic bacteria, such as Delftia, Stenotrophomonas, Sphingobacterium, Rhodococcus, Devosia, Ensifer, and Psychrobacter were predominantly detected in patients with CRC without lymph node metastasis. The diagnostic prediction was evaluated using the CatBoost algorithm; these microbes presented high diagnostic accuracy with a receiver operating characteristics-area under curve of 0.8, which was validated using qPCR. In conclusion, this study identified specific aerobic microbial groups as non-invasive biomarkers for early diagnosis in patients with CRC without genetic or environmental factors.

目前检测大多数结直肠息肉和早期肿瘤的方法缺乏足够的灵敏度和特异性,可能会阻碍治疗并最终降低生存率。在此,我们进行了元基因组分析,以确定早期结直肠癌(CRC)患者粪便样本中的微生物组标记。我们比较了 CRC 患者和健康人之间的肠道微生物群组成,特别关注早期 CRC 患者,即没有诊断 CRC 的核心突变(KRAS、BRAF)、稳定的微卫星不稳定性和远处转移的患者。我们的研究旨在通过 16S rRNA 扩增子测序,从结直肠癌(CRC)患者不同癌症阶段的肠道微生物群中找出潜在的生物标记物,从而为早期诊断 CRC 提出一种新的无创方法。根据 TNM 标准分为两组,一组仅按肿瘤大小分类(命名为 T 组),另一组按淋巴结转移分类(命名为 TN 组)。在无淋巴结转移的 CRC 患者中主要检测到需氧菌,如 Delftia、Stenotrophomonas、Sphingobacterium、Rhodococcus、Devosia、Ensifer 和 Psychrobacter。使用 CatBoost 算法对诊断预测进行了评估;这些微生物具有很高的诊断准确性,其接收者操作特征曲线下面积为 0.8,并通过 qPCR 进行了验证。总之,这项研究确定了特定需氧微生物群作为非侵入性生物标志物,可用于无遗传或环境因素的 CRC 患者的早期诊断。
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引用次数: 0
Effects of Limosilactobacillus reuteri DSM 17938 in neonates exposed to antibiotics: a randomised controlled trial. 抗生素对新生儿的影响:随机对照试验。
IF 3 4区 医学 Q2 MICROBIOLOGY Pub Date : 2024-10-31 DOI: 10.1163/18762891-bja00049
J Lozar Krivec, P Bratina, A Valcl, K Lozar Manfreda, A Petrovčič, E Benedik, T Obermajer, B Bogovič Matijašić, U Šetina, M Rupnik, A Mahnič, D Paro-Panjan

Perinatal antibiotic exposure potentially leads to gut microbiota dysbiosis, which is associated with functional gastrointestinal disorders (FGIDs). We aimed to investigate the effects of Limosilactobacillus reuteri DSM 17938 supplementation on the development of FGIDs, crying and sleep duration, and the gut microbial composition in infants exposed to antibiotics during the neonatal period. In this randomised, double-blind, placebo-controlled study, we included 89 term neonates treated with antibiotics. Neonates received the study product for six weeks. FGIDs, assessed by the Infant Gastrointestinal Symptom Questionnaire, crying and sleep duration were assessed at four and eight weeks, and six months after enrolment. Faecal samples were collected six weeks and twelve months after enrolment. The gut microbial community composition was analysed using 16S amplicon sequencing and qPCR. The proportion of infants with FGIDs was greater in the control group, although the difference between the groups was significant only six months after enrolment. At all time points, the probiotic group presented a longer sleep duration and shorter crying time than the control group, but the difference was not statistically significant. Probiotic consumption had no significant effect on the gut microbiota composition except for increased L. reuteri DSM 17938 abundance in the probiotic group at six weeks after enrolment. At specific time points after supplementation with L. reuteri DSM 17938, a reduction in the prevalence of FGIDs was observed in the probiotic group. However, no observable effect on the gut microbiota was detected during the intervention. We believe that probiotic supplementation in neonates during and after antibiotic treatment to minimise the negative effects of antibiotics on gut function during this vulnerable period of human development warrants further investigation. The trial is registered at ClinicalTrials.gov (NCT02865564).

围产期抗生素暴露可能导致肠道微生物菌群失调,而肠道微生物菌群失调与功能性胃肠道疾病(FGIDs)有关。我们的目的是研究在新生儿期接触抗生素的婴儿中补充柠檬酸嗜酸乳杆菌(DSM 17938)对功能性胃肠失调症的发展、哭闹和睡眠时间以及肠道微生物组成的影响。在这项随机、双盲、安慰剂对照研究中,我们纳入了 89 名接受抗生素治疗的足月新生儿。新生儿接受了为期六周的研究产品治疗。入组后 4 周、8 周和 6 个月时,通过婴儿胃肠道症状问卷评估 FGID、哭闹和睡眠时间。入学后六周和十二个月收集粪便样本。采用 16S 扩增子测序和 qPCR 分析了肠道微生物群落的组成。对照组患 FGID 的婴儿比例更高,但两组间的差异仅在入学六个月后才显著。在所有时间点上,益生菌组都比对照组睡眠时间更长、哭闹时间更短,但差异在统计学上并不显著。服用益生菌对肠道微生物群的组成没有明显影响,只是在入学六周后,益生菌组中的 L. reuteri DSM 17938 丰度有所增加。在补充 L. reuteri DSM 17938 后的特定时间点,观察到益生菌组的 FGID 发病率有所下降。然而,在干预过程中并未发现对肠道微生物群有明显的影响。我们认为,在抗生素治疗期间和治疗后为新生儿补充益生菌,以尽量减少抗生素在人体发育的这一脆弱时期对肠道功能的负面影响,值得进一步研究。该试验已在 ClinicalTrials.gov 上注册(NCT02865564)。
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引用次数: 0
In vitro validation of colon delivery of vitamin B2 through a food grade multi-unit particle system. 通过食品级多单位颗粒系统向结肠输送维生素 B2 的体外验证。
IF 3 4区 医学 Q2 MICROBIOLOGY Pub Date : 2024-10-29 DOI: 10.1163/18762891-bja00045
R E Steinert, W Sybesma, R Duss, A Rehman, M Watson, T C van den Ende, E Funda

Colon target delivery of active ingredients is frequently applied in pharmaceutical products. However, in functional food and beverage applications, dietary supplements, and medical nutrition, formats targeting colonic delivery to improve human health are rare. Nevertheless, there is emerging evidence for beneficial effects of colonic delivered nutrients on gut microbiota and host health which increases the demand for sustainable food grade materials that are regulatory approved for application. In this paper, we describe a double layer coated multi-unit particle system (MUPS) with a diameter of approximately 730 microns consisting of food grade materials: shellac as outer layer, alginate as inner layer, cellulose as a core and riboflavin as active ingredient. The suitability of the MUPS for colonic delivery was tested in three well-established in vitro digestion and fermentation models: the USP Apparatus 3 and the TNO Intestinal Models 1 and 2 (TIM-1 and TIM-2). All systems confirmed the integrity of the MUPS under simulated upper gastrointestinal tract conditions with approximately 90% of the active ingredient being released under simulated ileal-colonic conditions. The TIM-2 model also showed the effects of riboflavin loaded MUPS on the microbiome composition with an increase in the production of short-chain fatty acids, acetate and butyrate. The results of these experiments provide a reliable basis for validation of this vitamin-loaded food grade MUPS in future human clinical trials. In addition, following the recent announcement of the European Commission to restrict intentionally added microplastics to products, the materials used in the described formulation offer an environmentally friendly alternative to often applied methyl acrylate based coatings.

活性成分的结肠靶向给药经常被应用于医药产品中。然而,在功能性食品和饮料应用、膳食补充剂和医疗营养品中,针对结肠给药以改善人体健康的形式却很少见。然而,有新的证据表明,通过结肠输送的营养物质对肠道微生物群和宿主健康有益,这就增加了对获得监管部门批准应用的可持续食品级材料的需求。在本文中,我们介绍了一种直径约为 730 微米的双层涂层多单元颗粒系统(MUPS),该系统由食品级材料组成:外层为虫胶,内层为海藻酸盐,核心为纤维素,活性成分为核黄素。在三种成熟的体外消化和发酵模型中测试了 MUPS 的结肠给药适用性:USP Apparatus 3 和 TNO Intestinal Models 1 和 2(TIM-1 和 TIM-2)。所有系统都证实了 MUPS 在模拟上消化道条件下的完整性,在模拟回肠结肠条件下,约 90% 的活性成分被释放出来。TIM-2 模型还显示了核黄素负载 MUPS 对微生物群组成的影响,短链脂肪酸、乙酸盐和丁酸盐的产量有所增加。这些实验结果为在未来的人体临床试验中验证这种富含维生素的食品级 MUPS 提供了可靠的依据。此外,在欧盟委员会最近宣布限制在产品中有意添加微塑料之后,所述配方中使用的材料为经常使用的丙烯酸甲酯涂层提供了一种环保型替代品。
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引用次数: 0
Oral supplementation of heat-killed Enterococcus faecalis strain EC-12 relieves gastrointestinal discomfort and alters the gut microecology in academically stressed students. 口服热处理杀死的粪肠球菌 EC-12 菌株可缓解学业紧张学生的肠胃不适并改变肠道微生态。
IF 3 4区 医学 Q2 MICROBIOLOGY Pub Date : 2024-10-29 DOI: 10.1163/18762891-bja00046
J Li, T Terajima, H Liu, S Miyata, J Kambe, Y Makioka-Itaya, R Inoue, Y Yamamoto, K Nagaoka

Stress significantly affects gastrointestinal and mental health, and the gut microbiota plays a pivotal role in this process. Enterococcus faecalis strain EC-12 (EC-12) is a lactic acid bacterium that has several health benefits. To investigate the impact of oral supplementation with heat-killed EC-12 on the discomfort caused by stress, a randomised, double-blind, placebo-controlled trial was conducted with students under academic stress taking EC-12 (n = 14) or a placebo (n = 13) daily for one week. Improvement in the students' symptoms was assessed using the visual analogue scale. Faecal microbiota was characterised by next-generation sequencing of 16S rRNA genes, and faecal metabolites and short-chain fatty acids were analysed using a GC-MS metabolomics approach. Significant improvements in abdominal pain and rumbling of the stomach were found in the EC-12 group compared to the placebo group, but no changes were observed in mental symptoms or salivary cortisol levels. The relative abundance of E. faecalis significantly increased in the EC-12 group after the trial; however, the composition and diversity of the gut microbiota did not change significantly. Functional analysis of the gut microbiota suggested that EC-12 intake alters specific metabolic pathways. Although the levels of faecal short-chain fatty acids did not change between the groups before and after the trial, EC-12 intake altered the composition of faecal metabolites, with a significant increase in tryptamine levels. The ratio of students with improved symptoms to those with increased tryptamine levels was calculated based on the number of students with elevated faecal tryptamine levels who showed symptomatic improvements. The ratio of improved rumbling stomach was higher than that of other types of digestive discomfort. These results suggest that oral supplementation with EC-12 has a potentially beneficial effect on stress-induced gastrointestinal discomfort, which may occur through alterations in gut microbiota composition and metabolism. This study was registered at the University Hospital Medical Information Network Center (UMIN) under the UMIN ID: UMIN000048184.

压力会严重影响肠胃和心理健康,而肠道微生物群在这一过程中发挥着关键作用。粪肠球菌菌株 EC-12 (EC-12)是一种乳酸菌,对健康有多种益处。为了研究口服热杀死的EC-12对压力引起的不适的影响,我们进行了一项随机、双盲、安慰剂对照试验,让学习压力大的学生每天服用EC-12(14人)或安慰剂(13人),持续一周。采用视觉模拟量表评估学生症状的改善情况。通过对 16S rRNA 基因进行下一代测序来确定粪便微生物群的特征,并采用 GC-MS 代谢组学方法分析粪便代谢物和短链脂肪酸。与安慰剂组相比,EC-12 组的腹痛和胃部咕噜声明显改善,但精神症状或唾液皮质醇水平未见变化。试验后,EC-12 组中粪肠球菌的相对丰度明显增加,但肠道微生物群的组成和多样性没有发生显著变化。肠道微生物群的功能分析表明,摄入EC-12会改变特定的代谢途径。虽然试验前后各组之间粪便短链脂肪酸的含量没有变化,但EC-12的摄入改变了粪便代谢物的组成,色胺含量显著增加。根据症状得到改善的粪便色胺水平升高的学生人数,计算出症状得到改善的学生人数与色胺水平升高的学生人数之比。胃部不适症状得到改善的比例高于其他类型的消化道不适症状。这些结果表明,口服EC-12对压力引起的胃肠道不适具有潜在的有益作用,这种作用可能是通过改变肠道微生物群的组成和代谢而产生的。本研究已在大学医院医学信息网络中心(UMIN)注册,注册号为 UMIN ID:UMIN000048184。
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引用次数: 0
Impact of two human milk oligosaccharides and lactose on the faecal microbiome of infants with probable cow's milk allergy. 两种人乳低聚糖和乳糖对可能对牛奶过敏的婴儿粪便微生物群的影响。
IF 3 4区 医学 Q2 MICROBIOLOGY Pub Date : 2024-10-25 DOI: 10.1163/18762891-bja00048
P Van den Abbeele, R G Heine, M Van de Vliet, L Favre, H L P Tytgat, N Sprenger, S Deyaert, A Baudot, S Nutten

Cow's milk protein allergy (CMPA) in infancy is associated with intestinal microbial dysbiosis, characterised by low Bifidobacteriaceae levels. The present study aimed to investigate the impact of two human milk oligosaccharides (HMO), lactose (L), and their combination on the faecal microbiome and metabolome of infants with CMPA. Stool samples of 12 term infants with probable CMPA (mean age 4.3 months) were analysed using a validated intestinal fermentation assay (SIFR® technology). For each substrate (i.e. HMO (2'-fucosyllactose [2'-FL] and lacto-N-neotetraose [LNnT]), L and HMO + L), taxonomic microbiome characterisation and untargeted metabolite profiling were performed at multiple timepoints. At baseline, the tested faecal microbiota overall displayed low abundances of Bifidobacteriaceae. Fermentation with either HMO or lactose significantly enriched Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium pseudocatenulatum and, for HMO + L, also Bifidobacterium bifidum. The increase in HMO-utilising bifidobacteria was associated with a significant rise in levels of short-chain fatty acids, aromatic lactic acids and N-acetylated amino acids, with additive effects being observed for HMO + L. The above data suggest that the combination of 2'-FL, LNnT and lactose helps to alleviate the previously reported CMPA-associated intestinal bacterial dysbiosis and induces the production of several beneficial metabolites. The clinical significance of these findings for infants with CMPA requires further investigation.

婴儿期牛奶蛋白过敏(CMPA)与肠道微生物菌群失调有关,其特征是双歧杆菌含量低。本研究旨在探讨两种人乳低聚糖(HMO)、乳糖(L)及其组合对 CMPA 婴儿粪便微生物组和代谢组的影响。我们使用一种经过验证的肠道发酵测定法(SIFR® 技术)对 12 名可能患有 CMPA 的足月婴儿(平均年龄 4.3 个月)的粪便样本进行了分析。针对每种底物(即 HMO(2'-岩藻酰半乳糖 [2'-FL] 和乳-N-新四糖 [LNnT])、L 和 HMO + L),在多个时间点进行了微生物群分类特征描述和非靶向代谢物分析。在基线时,受测粪便微生物群总体上显示出双歧杆菌的低丰度。用 HMO 或乳糖发酵后,前列双歧杆菌、长双歧杆菌、假双歧杆菌明显增多,HMO + L 发酵时,双歧杆菌也明显增多。HMO 利用型双歧杆菌的增加与短链脂肪酸、芳香族乳酸和 N-乙酰化氨基酸水平的显著上升有关,而 HMO + L 则具有叠加效应。上述数据表明,2'-FL、LNnT 和乳糖的组合有助于缓解之前报道的与 CMPA 相关的肠道细菌失调,并诱导产生多种有益代谢物。这些发现对患有 CMPA 的婴儿的临床意义还需要进一步研究。
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引用次数: 0
Lipid-lowering and antioxidant properties of probiotic Bifidobacterium animalis MSMC83 in rats on a high-fat diet. 高脂饮食大鼠体内益生菌动物双歧杆菌 MSMC83 的降脂和抗氧化特性
IF 3 4区 医学 Q2 MICROBIOLOGY Pub Date : 2024-10-11 DOI: 10.1163/18762891-bja00043
C Chantarangkul, P Phuengmaung, A Leelahavanichkul, P Piewngam, M Otto, M Taweechotipatr

Hyperlipidaemia, the abnormally high concentration of lipids such as cholesterol in the body, has a series of deleterious effects on health that are least in part are due to increased inflammation and oxidative stress. Probiotics are living microorganisms that possess the efficacy to improve health. Among the many effects that have been ascribed to probiotics is the potential to lower the body lipid content. Here, we used a rat model of induced hyperlipidaemia to assess the lipid-lowering and antioxidant properties of the probiotic strain Bifidobacterium animalis MSMC83 as well as its impact on intestinal barrier immunity and the intestinal microbiota. Oral probiotic intake led to a reduction of body weight, fasting blood glucose, and lipid levels, and increased expression of cholesterol-7α-hydroxylase and antioxidant enzymes. Additionally, B. animalis MSMC83 decreased the levels of liver enzymes and pro-inflammatory cytokines, leading to reduced hepatic steatosis. Furthermore, it re-established intestinal barrier integrity as shown by restoration of the tight junction protein zonula occludens-1 amount and reduced pathogen-induced inflammation in the intestinal epithelium as shown by readjusted expression of toll-like receptors (TLRs). Moreover B. animalis MSMC83 contributed to the maintenance of a balanced, diverse microbiome. Thus, our results indicate that B. animalis MSMC83 alleviates risk factors associated with hyperlipidaemia, suggesting its use as a probiotic to counter the effects associated with unhealthy diets.

高脂血症是指人体内胆固醇等脂质的浓度异常增高,对健康产生一系列有害影响,其中至少有一部分是由于炎症和氧化应激增加所致。益生菌是活的微生物,具有改善健康的功效。在益生菌的众多功效中,有一种功效是可以降低体内脂质含量。在这里,我们利用大鼠诱导高脂血症模型来评估益生菌株动物双歧杆菌 MSMC83 的降脂和抗氧化特性,以及它对肠道屏障免疫和肠道微生物群的影响。口服益生菌可降低体重、空腹血糖和血脂水平,增加胆固醇-7α-羟化酶和抗氧化酶的表达。此外,B. animalis MSMC83 还降低了肝酶和促炎细胞因子的水平,从而减轻了肝脂肪变性。此外,它还重建了肠道屏障的完整性,这体现在紧密连接蛋白 Zonula occludens-1 数量的恢复上,并减少了病原体诱发的肠上皮炎症,这体现在收费样受体(TLRs)表达的重新调整上。此外,B. animalis MSMC83 还有助于维持平衡、多样的微生物群。因此,我们的研究结果表明,B. animalis MSMC83 可减轻与高脂血症相关的风险因素,建议将其用作一种益生菌,以对抗与不健康饮食相关的影响。
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引用次数: 0
A convenient and versatile culturomics platform to expand the human gut culturome of Lachnospiraceae and Oscillospiraceae. 一个方便、多功能的培养组学平台,用于扩展人类肠道 Lachnospiraceae 和 Oscillospiraceae 的培养组。
IF 3 4区 医学 Q2 MICROBIOLOGY Pub Date : 2024-10-09 DOI: 10.1163/18762891-bja00042
N Plomp, L Liu, L Walters, C Bus-Spoor, M T Khan, P O Sheridan, A C M Veloo, A W Walker, H J M Harmsen, E Tsompanidou

The human gut microbiota is increasingly being recognised to play an important role in maintaining health. The families Lachnospiraceae and Oscillospiraceae in particular, are often reduced in disease states but are relatively poorly represented in culture collections. Cultured representatives are required to investigate the physiology and host interactions of gut microbes. Establishing cultured isolate collections can be laborious and expensive owing to the fastidious growth requirements of these organisms and the costs associated with taxonomic classification. This study proposes a culturomics platform combining a single basal culture medium with matrix-assisted laser adsorption/ionisation coupled to time-of-flight mass spectrometry (MALDI-TOF MS) for fast and reliable isolation and identification of hundreds of novel isolates. In this study, basal YCFA medium supplemented with either glucose, apple pectin, or porcine mucin was used to cultivate a total of 724 different isolates derived from only 11 different faecal samples from healthy volunteers, of which 389 isolates belonged to the Lachnospiraceae and Oscillospiraceae families. Moreover, 27 isolates could not be assigned to known species based on their 16S rRNA gene, 17 of which may even represent novel genera. To aid MALDI-TOF MS identification of gut bacteria, the commercial database was complemented with the MaldiGut database presented here, containing a collection of 132 different Main Spectrum Profiles, including the profiles of 125 Firmicutes species, 3 Bacteroidetes species, 3 Actinobacteria species, and one Verrucomicrobia species. The culturomics platform and MaldiGut database presented here will enable further expansion of the gut culturome, especially within the understudied Lachnospiraceae and Oscillospiraceae families.

人们越来越认识到,人类肠道微生物群在维持健康方面发挥着重要作用。特别是漆树科(Lachnospiraceae)和鹅膏蕈科(Oscillospiraceae),在疾病状态下往往会减少,但在培养物中却相对较少。研究肠道微生物的生理学和宿主相互作用需要培养代表。由于这些生物对生长要求苛刻,且分类成本高昂,因此建立培养分离菌种库既费力又昂贵。本研究提出了一种培养物组学平台,该平台将单一基础培养基与基质辅助激光吸附/电离耦合飞行时间质谱(MALDI-TOF MS)相结合,可快速可靠地分离和鉴定数百种新型分离物。在这项研究中,使用添加了葡萄糖、苹果果胶或猪粘蛋白的 YCFA 基础培养基培养了 724 个不同的分离菌株,这些菌株来自 11 个不同的健康志愿者粪便样本,其中 389 个分离菌株属于拉赫诺斯拉科(Lachnospiraceae)和奥斯基诺斯拉科(Oscillospiraceae)。此外,有 27 个分离物无法根据其 16S rRNA 基因归入已知物种,其中 17 个甚至可能代表新属。为了帮助 MALDI-TOF MS 鉴定肠道细菌,本文介绍的 MaldiGut 数据库对商业数据库进行了补充,该数据库包含 132 种不同的主光谱图谱,其中包括 125 种固着菌、3 种类杆菌、3 种放线菌和 1 种疣状微菌的图谱。本文介绍的培养组学平台和 MaldiGut 数据库将有助于进一步扩展肠道培养组,尤其是研究不足的 Lachnospiraceae 和 Oscillospiraceae 家族。
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引用次数: 0
Effects of complex probiotics on intestinal function and its regulatory mechanism in patients with constipation. 复合益生菌对便秘患者肠道功能及其调节机制的影响
IF 3 4区 医学 Q2 MICROBIOLOGY Pub Date : 2024-10-04 DOI: 10.1163/18762891-bja00039
X Zhang, Y Jia, X Li, X Wang, L Li, P Zhang, X Dong, X Ze, Y An, J Li

Chronic constipation is a multi-symptomatic, multifactorial, and heterogeneous gastrointestinal disorder. Current pharmacological treatments for chronic constipation are limited and might negatively impact the patients' quality of life. Although probiotics have been shown to improve constipation symptoms, their specific regulatory mechanisms remain unclear. This study sought to explore how probiotic complexes may affect chronic constipation by improving patients' defecation habits. Furthermore, microbial profiles and non-targeted metabolites were assessed to explore the metabolic pathways involved in the improvement of constipation by probiotics. Patients with chronic constipation were treated using a single-blind, randomised, placebo-controlled trial design. The experimental group was administered Lactobacillus powder prepared from 15 probiotic products, and maltodextrin was used as a placebo. Samples were collected twice daily for 4 weeks, and faecal samples were analysed using 16S rRNA sequencing and untargeted metabolic histology. Probiotic treatment changed the makeup of the gut microbiota, enhanced the quantity of Bifidobacterium and Lactobacillus, and markedly reduced clinical symptoms. The 16S rRNA analysis revealed that the abundance of Bifidobacterium and Prevotella increased while that of Thickettsia declined. Moreover, there was a decrease in the abundance of Faecalibacterium and Roseburia. Non-targeted metabolomics analysis identified several differential metabolites, including succinic acid, fumaric acid, cholesterol, xanthurenic acid, 3-alpha,7-alpha-trihydroxy-5beta-cholestan-26-oic, and N-methyltryptamine. KEGG analysis showed that these metabolites were mainly associated with metabolic pathways such as primary bile acid biosynthesis, tryptophan metabolism, alanine, aspartate and glutamate metabolism, phenylalanine metabolism, cholesterol metabolism, and propanoate metabolism. In this study, gut microbiome and non-targeted metabolome analyses were performed on collected faecal samples to compare characteristic microorganisms and differential metabolites to provide new insights and references for probiotic intervention in constipation. Trial registered at chictr.org.cn under number: ChiCTR2200056274.

慢性便秘是一种多症状、多因素和异质性胃肠道疾病。目前针对慢性便秘的药物治疗非常有限,可能会对患者的生活质量产生负面影响。虽然益生菌已被证明能改善便秘症状,但其具体的调节机制仍不清楚。本研究试图探讨益生菌复合物如何通过改善患者的排便习惯来影响慢性便秘。此外,还对微生物谱和非靶向代谢物进行了评估,以探索益生菌改善便秘所涉及的代谢途径。慢性便秘患者采用单盲、随机、安慰剂对照试验设计进行治疗。实验组服用从 15 种益生菌产品中制备的乳酸菌粉,麦芽糊精作为安慰剂。实验组连续 4 周每天收集两次样本,并使用 16S rRNA 测序和非靶向代谢组织学方法对粪便样本进行分析。益生菌治疗改变了肠道微生物群的构成,增加了双歧杆菌和乳酸杆菌的数量,并明显减轻了临床症状。16S rRNA分析显示,双歧杆菌和普雷沃氏菌的数量增加了,而厚壁菌的数量则下降了。此外,粪杆菌和玫瑰糠疹菌的数量也有所减少。非靶向代谢组学分析发现了几种不同的代谢物,包括琥珀酸、富马酸、胆固醇、黄嘌呤酸、3-alpha,7-alpha-三羟基-5beta-胆甾烷-26-酸和 N-甲基色胺。KEGG 分析显示,这些代谢物主要与初级胆汁酸生物合成、色氨酸代谢、丙氨酸、天门冬氨酸和谷氨酸代谢、苯丙氨酸代谢、胆固醇代谢和丙酸代谢等代谢途径有关。本研究对收集的粪便样本进行了肠道微生物组和非靶向代谢组分析,以比较特征微生物和差异代谢物,从而为益生菌干预便秘提供新的见解和参考。试验注册于 Chictr.org.cn,编号:ChiCTR2200056274:ChiCTR2200056274。
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引用次数: 0
Perinatal administration of Saccharomyces cerevisiae UFMG A-905 prevents asthma development in the offspring of mice. 围产期服用酿酒酵母 UFMG A-905 可预防小鼠后代哮喘的发生。
IF 3 4区 医学 Q2 MICROBIOLOGY Pub Date : 2024-09-27 DOI: 10.1163/18762891-bja00044
C M Sandy, C C Guimarães, V M B Fonseca, J R Nicoli, F S Martins, M C Borges

Asthma prevalence has been increasing in communities that become more urbanised. Our previous results showed that Saccharomyces cerevisiae UFMG A-905 prevented the development of asthma symptoms and characteristics in a dose-dependent manner. Perinatal programming theory proposes that early exposure to some stimuli may have a protective effect in adult life. The aim of this study was to evaluate the effects of perinatal administration of S. cerevisiae UFMG A-905 in the prevention of asthma in the offspring of mice. S. cerevisiae UFMG A-905 was cultured in YPD broth medium and administered to three groups of mice: before conception, during gestation and lactation (CGL group); during gestation and lactation (GL group); and only during lactation (L group). The offspring of these animals were sensitised and challenged with ovalbumin. Two control groups received saline in the same periods. After, in vivo measurements of airway hyperresponsiveness (AHR) were performed. Total and differential cell count in bronchoalveolar lavage (BAL); ELISA for interleukin (IL)-4, IL-5, IL-10, IL-13, and IL-17A in the lung homogenate or BAL; and ELISA for ovalbumin (OVA)-specific immunoglobulin E (IgE) were performed. The animals of the CGL, GL, and L group, when compared to the OVA group, presented a significant reduction of AHR ( P < 0.01), levels of IL-5 ( P < 0.001) in BAL, and IL-4 ( P < 0.05) and IL-13 ( P < 0.01) in the lung homogenate. Serum IgE levels were significantly higher ( P < 0.05) in CGL and GL groups when compared to the OVA group, but not in the L group. Only in the group L, there was a significant decrease in the number of total cells ( P < 0.01) and eosinophils ( P < 0.05). Perinatal administration of S. cerevisiae UFMG A-905 prevented the development of asthma-like characteristics and may be an option for asthma management. The protective effects on the offspring were more prominent when the yeast was given during lactation.

随着城市化进程的加快,哮喘发病率也在不断上升。我们之前的研究结果表明,酵母菌 UFMG A-905 能以剂量依赖的方式防止哮喘症状和特征的发展。围产期编程理论认为,早期接触某些刺激可能会对成年后的生活产生保护作用。本研究的目的是评估围产期服用 S. cerevisiae UFMG A-905 对预防小鼠后代哮喘的影响。在 YPD 肉汤培养基中培养 S. cerevisiae UFMG A-905,并给三组小鼠施用:受孕前、妊娠期和哺乳期(CGL 组);妊娠期和哺乳期(GL 组);仅哺乳期(L 组)。这些动物的后代接受卵清蛋白的致敏和挑战。两个对照组在同一时期接受生理盐水。之后,对气道高反应性(AHR)进行体内测量。对支气管肺泡灌洗液(BAL)中的总细胞数和差异细胞数、肺匀浆或BAL中的白细胞介素(IL)-4、IL-5、IL-10、IL-13和IL-17A进行了ELISA检测,并对卵清蛋白(OVA)特异性免疫球蛋白E(IgE)进行了ELISA检测。与OVA组相比,CGL、GL和L组动物的AHR(P<0.01)、BAL中IL-5(P<0.001)、肺匀浆中IL-4(P<0.05)和IL-13(P<0.01)水平均显著降低。与OVA组相比,CGL组和GL组的血清IgE水平明显升高(P < 0.05),但L组没有升高。只有 L 组的总细胞数(P < 0.01)和嗜酸性粒细胞数(P < 0.05)明显减少。围产期服用 S. cerevisiae UFMG A-905 可预防哮喘样特征的发展,可能是治疗哮喘的一种选择。在哺乳期服用酵母菌对后代的保护作用更为显著。
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引用次数: 0
Characterisation of potential anti-inflammatory next-generation probiotics resistant to bisphenol A. 抗双酚 A 的潜在抗炎下一代益生菌的特征。
IF 3 4区 医学 Q2 MICROBIOLOGY Pub Date : 2024-09-27 DOI: 10.1163/18762891-bja00041
A López-Moreno, C Carbonne, C Kropp, D Rios-Covian, F Pepke, P Langella, M Aguilera, R Martin

The world is witnessing an increasing incidence of chronic non-communicable diseases (NCDs), such as inflammatory bowel disease (IBD), a group of complex gastrointestinal disorders characterised by inflammation. It is believed that environmental factors, such as exposure to pollutants and endocrine-disrupting chemicals (i.e. bisphenol A [BPA]), are playing a role in IBD pathophysiology. New research suggests a potential treatment solution: next-generation probiotic (NGP) strains isolated from human gut microbiota that can biodegrade xenobiotics and thus possibly modulate IBD triggered by these xenobiotics. In this study, we hypothesised that specific BPA-tolerant bacteria would exhibit beneficial, anti-inflammatory properties that could counter the effects of BPA exposure and concomitantly reduce colitis severity. We observed that two such strains, Bacillus sp. AM1 and Paeniclostridium sp., exhibited potential anti-inflammatory properties in vitro and in vivo. First, these bacteria were able to decrease the secretion of interleukin (IL)-8 cytokines by HT-29 cells that had been exposed to the proinflammatory cytokine tumour necrosis factor (TNF)-α. Second, when treated with Bacillus sp. AM1 and Paeniclostridium sp. (this latter had a stronger reducing effect on inflammatory markers), mice with chemically induced colitis displayed lower levels of colon damage, monocyte chemotactic protein 1 (MCP-1), lipocalin-2 (LCN-2), and proinflammatory cytokines (IL-1β and IL-6). Future research should clarify the underlying mechanisms at play and identify potential strategies for counteracting the systemic effects of IBD, including those exacerbated by BPA exposure. Our results suggest that one such strategy could be treatment with BPA-tolerant bacteria that possess anti-inflammatory properties.

全球慢性非传染性疾病(NCDs)的发病率不断上升,如炎症性肠病(IBD),这是一组以炎症为特征的复杂胃肠道疾病。人们认为,环境因素,如暴露于污染物和干扰内分泌的化学物质(如双酚 A [BPA]),在 IBD 病理生理学中起着一定的作用。新的研究提出了一种潜在的治疗方案:从人类肠道微生物群中分离出的下一代益生菌(NGP)菌株可以生物降解异种生物,从而可能调节由这些异种生物引发的 IBD。在这项研究中,我们假设耐受双酚 A 的特定细菌会表现出有益的抗炎特性,可以抵消双酚 A 暴露的影响,同时减轻结肠炎的严重程度。我们观察到,两种这样的菌株--AM1芽孢杆菌和Paeniclostridium sp.--在体外和体内都表现出潜在的抗炎特性。首先,这些细菌能够减少暴露于促炎细胞因子肿瘤坏死因子(TNF)-α的 HT-29 细胞分泌的白细胞介素(IL)-8 细胞因子。其次,当使用芽孢杆菌 AM1 和梭状芽孢杆菌(后者对炎症标志物有更强的抑制作用)治疗时,化学诱导的结肠炎小鼠的结肠损伤、单核细胞趋化蛋白 1(MCP-1)、脂钙蛋白-2(LCN-2)和促炎细胞因子(IL-1β 和 IL-6)水平较低。未来的研究应阐明潜在的作用机制,并确定抵消 IBD 全身影响的潜在策略,包括因暴露于双酚 A 而加剧的影响。我们的研究结果表明,其中一种策略可能是使用具有抗炎特性的耐 BPA 细菌进行治疗。
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引用次数: 0
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