Short-chain fatty acid

短链脂肪酸
  • 文章类型: Journal Article
    1.这项研究是为了确定植酸酶的分级水平对性能的影响,白蛋鸡的蛋品质和肠道健康2.治疗包括含有0.14%有效磷(avP)的阴性对照(NC)饮食,阳性对照(PC)饮食中含有0.35%的avP,通过磷酸二钙(DCP)和DCP在PC中被三个分级水平的植酸酶所替代,这些植酸酶来自于500(PC-500)的Komagataellaphafii,750(PC-750)和1000(PC-1000)FTU/kg,提供0.176%,AVP的0.188%和0.200%,分别.3.鸡蛋生产,饲料摄入量,在NC喂养的鸟类中,饲料转化率和空肠形态计量学受到负面影响(p<0.05)。考虑到整个时期,饲喂添加分级水平植酸酶的日粮的禽类与PC禽类具有相同的产蛋量和采食量(p<0.05)。饲料转化率显著降低4.9%,与饲喂PC的母鸡相比,饲喂PC-500,PC-750和PC-1000的母鸡分别为1.6%和7.6%(p<0.05)。两种饮食处理都不影响破裂的鸡蛋,脏鸡蛋,蛋壳断裂强度和蛋壳厚度。日粮补充植酸酶使绒毛表面积显著增加15%,36%和40%在PC-500,PC-750和PC-1000鸟,分别与PC相比(p<0.05)。观察到乳杆菌计数的显著增加与植酸酶水平的增加一致(p<0.05)。饮食治疗对盲肠大肠杆菌或有氧人群没有影响。此外,植酸酶显著提高了盲肠总短链脂肪酸浓度(SCFA;p<0.01)。总之,随着性能参数的改善,在蛋鸡日粮中加入植酸酶可以改善肠道形态,刺激盲肠微生物区系并增加SCFA浓度。
    1. This study was conducted to determine the effects of graded levels of phytase on the performance, egg quality and gut health of white laying hens.2. Treatments consisted of a negative control (NC) diet containing 0.14% available phosphorus (avP), positive control (PC) diet containing 0.35% avP provided via dicalcium phosphate (DCP) and DCP replaced in the PC by with three graded levels of phytase derived from Komagataella phaffii at 500 (PC-500), 750 (PC-750) and 1000 (PC-1000) FTU/kg which provided 0.176%, 0.188% and 0.200% of avP, respectively.3. Egg production, feed intake, feed conversion ratio and jejunal morphometry were negatively affected in NC-fed birds (p < 0.05). Considering the whole period, birds fed a diet supplemented with graded levels of phytase shared the same egg production and feed intake levels with PC birds (p < 0.05). Feed conversion ratio was significantly lowered by 4.9%, 1.6% and 7.6% in hens fed on diets PC-500, PC-750 and PC-1000, respectively compared to those fed the PC (p < 0.05).4. Neither of the dietary treatments affected cracked eggs, dirty eggs, eggshell breaking strength and eggshell thickness. Dietary supplementation of phytase significantly increased villus surface area by 15%, 36% and 40% in PC-500, PC-750 and PC-1000 birds, respectively compared to PC (p < 0.05).5. A significant increase in lactobacillus count was observed in line with increasing the level of phytase (p < 0.05). Dietary treatments had no effect on the caecal coliform or aerobic populations. Furthermore, phytase supplementation significantly increased the concentrations of total caecal short-chain fatty acid (SCFA; p < 0.01).6. In conclusion, along with improving performance parameters, the inclusion of phytase in laying hen diets can ameliorate intestinal morphology and stimulate caecal microflora and increase SCFA concentrations.
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  • 文章类型: Journal Article
    蒙古族具有独特的饮食习惯,其特征是肉类和奶制品的消费量高,蔬菜少,导致东亚肥胖率最高。虽然肥胖是2型糖尿病(T2D)的已知原因,在这一人群中,T2D率是中等的;这被称为“蒙古悖论”。“由于肠道微生物群在能量和代谢稳态中起着关键作用,作为食物和身体之间的界面,我们调查了在蒙古人中参与预防T2D与肥胖同时发生的肠道微生物因素。我们比较了患有T2D(DO:n=31)或没有T2D(NDO:n=35)的肥胖蒙古族成年人的肠道微生物组和代谢组。在DO组的肠道微生物组中发现了生物异常特征;较低水平的Faecalibacterium和厌氧菌,被称为短链脂肪酸(SCFA)生产者和较高水平的Methanobrevibacter,Desulfovibrio,和已知与某些疾病相关的Solobacterium。另一方面,NDO组表现出更高水平的粪便SCFA浓度,特别是醋酸盐。这与整个鸟枪宏基因组分析的结果一致,这表明,在NDO组中,主要由厌氧菌hadrus编码的SCFA生物合成相关基因的相对丰度较高。包括宿主人口统计学参数的多逻辑回归分析表明,乙酸盐对T2D的发作具有最高的负面影响。这些发现表明,由肠道微生物群落产生的SCFA参与预防蒙古人肥胖中T2D的发展。
    Mongolian people possess a unique dietary habit characterized by high consumption of meat and dairy products and fewer vegetables, resulting in the highest obesity rate in East Asia. Although obesity is a known cause of type 2 diabetes (T2D), the T2D rate is moderate in this population; this is known as the \"Mongolian paradox.\" Since the gut microbiota plays a key role in energy and metabolic homeostasis as an interface between food and body, we investigated gut microbial factors involved in the prevention of the co-occurrence of T2D with obesity in Mongolians. We compared the gut microbiome and metabolome of Mongolian adults with obesity with T2D (DO: n = 31) or without T2D (NDO: n = 35). Dysbiotic signatures were found in the gut microbiome of the DO group; lower levels of Faecalibacterium and Anaerostipes which are known as short-chain fatty acid (SCFA) producers and higher levels of Methanobrevibacter, Desulfovibrio, and Solobacterium which are known to be associated with certain diseases. On the other hand, the NDO group exhibited a higher level of fecal SCFA concentration, particularly acetate. This is consistent with the results of the whole shotgun metagenomic analysis, which revealed a higher relative abundance of SCFA biosynthesis-related genes encoded largely by Anaerostipes hadrus in the NDO group. Multiple logistic regression analysis including host demographic parameters indicated that acetate had the highest negative contribution to the onset of T2D. These findings suggest that SCFAs produced by the gut microbial community participate in preventing the development of T2D in obesity in Mongolians.
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  • 文章类型: Journal Article
    炎症性肠病(IBD),以肠道慢性炎症为特征,是由几个因素引起的。在这些因素中,微生物因子与肠道微生物群相关,通过厌氧发酵产生短链脂肪酸(SCFA)。已知发酵食品调节肠道微生物群组成。Ganjang(GJ),一种全世界消费的传统的韩国发酵酱油,已被证明具有抗氧化剂,抗癌,抗结肠炎,和抗高血压活性。然而,它对肠道微生物群的影响仍然未知。在本研究中,我们旨在比较使用不同方法制造的GJ的抗炎作用,并研究其对肠道SCFA产生的影响。为了评估GJ在肠道中的抗炎作用,我们使用葡聚糖硫酸钠(DSS)诱导的结肠炎小鼠模型进行了动物实验。所有GJ样本均减轻了DSS诱导的结肠炎症状,包括减少结肠长度,通过抑制炎性细胞因子的表达。此外,GJ给药调节DSS诱导的结肠炎模型中的SCFA产生。总的来说,在DSS诱导的结肠炎模型中,GJ通过调节炎症和调节SCFA水平来减轻DSS诱导的症状,从而发挥抗炎作用。因此,GJ是一种有前途的发酵食品,具有预防IBD的潜力。
    Inflammatory bowel disease (IBD), characterized by chronic inflammation of the gut, is caused by several factors. Among these factors, microbial factors are correlated with the gut microbiota, which produces short-chain fatty acids (SCFAs) via anaerobic fermentation. Fermented foods are known to regulate the gut microbiota composition. Ganjang (GJ), a traditional fermented Korean soy sauce consumed worldwide, has been shown to exhibit antioxidant, anticancer, anti-colitis, and antihypertensive activities. However, its effects on the gut microbiota remain unknown. In the present study, we aimed to compare the anti-inflammatory effects of GJ manufactured using different methods and investigate its effect on SCFA production in the gut. To evaluate the antiinflammatory effects of GJ in the gut, we performed animal experiments using a mouse model of dextran sulfate sodium (DSS)-induced colitis. All GJ samples attenuated DSS-induced colitis symptoms, including reduced colonic length, by suppressing the expression of inflammatory cytokines. In addition, GJ administration modulated SCFA production in the DSS-induced colitis model. Overall, GJ exerted anti-inflammatory effects by reducing DSS-induced symptoms via regulation of inflammation and modulation of SCFA levels in a DSS-induced colitis model. Thus, GJ is a promising fermented food with the potential to prevent IBD.
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  • 文章类型: Journal Article
    家蚕(Bombyxmori)幼虫有望用作昆虫吞噬的成分。它们充满了营养,包括不可消化的蛋白质;然而,关于食用整个家蚕对肠道菌群的影响的研究很少。我们准备了含有家蚕幼虫粉(SLP)的定制饮食,并研究了随意饲喂SLP饮食对小鼠肠道菌群和短链脂肪酸(SCFA)含量的影响。我们发现,饲喂SLP饮食(SLP组)的小鼠盲肠和粪便微生物群的多样性增加,它们的肠道微生物群的组成与对照小鼠的不同。此外,属水平的微生物群分析表明,在SLP组中,Alistipes的比例,LachnoshileaeA2和RF39,与预防肥胖有关,显着增加,而螺杆菌和厌氧菌的比例,与肥胖有关,显着下降。此外,SLP组丁酸水平升高,和梭菌UCG014和LachnospiphaceaeFCS020被发现与丁酸的水平有关,主要的SCFA之一。这些发现表明,蚕粉可以用作昆虫食品,也可以改善肥胖。
    Silkworm (Bombyx mori) larvae are expected to be useful as an ingredient in entomophagy. They are full of nutrients, including indigestible proteins; however, there have been few studies on the effects of the consumption of the entire body of silkworms on the intestinal microflora. We prepared a customized diet containing silkworm larval powder (SLP), and investigated the effects of ad libitum feeding of the SLP diet on the intestinal microbiota and the amount of short-chain fatty acids (SCFAs) in mice. We found that the diversity of the cecal and fecal microbiota increased in the mice fed the SLP diet (SLP group), and that the composition of their intestinal microbiota differed from that of the control mice. Furthermore, a genus-level microbiota analysis showed that in the SLP group, the proportions of Alistipes, Lachnospiraceae A2, and RF39, which are associated with the prevention of obesity, were significantly increased, while the proportions of Helicobacter and Anaerotruncus, which are associated with obesity, were significantly decreased. Additionally, the level of butyrate was increased in the SLP group, and Clostridia UCG 014 and Lachnospiraceae FCS020 were found to be associated with the level of butyrate, one of the major SCFAs. These findings indicated that silkworm powder may be useful as an insect food that might also improve obesity.
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  • 文章类型: Journal Article
    先前的研究表明,克罗恩病(CD)患者的健康一级亲属(HFDRs)的肠道微生物与CD的发展之间没有相关性。这里,我们利用HFDRs作为对照来检查活跃(CD-A)和静止(CD-R)CD个体的微生物群和代谢组,从而最大限度地减少遗传和环境因素的影响。与非相对对照相比,使用HFDR对照可以识别出更少的差异分类单元。粪杆菌,Dorea,CD-R中镰刀菌减少,独立于炎症,并与粪便短链脂肪酸(SCFA)相关。使用大型多中心队列进行的验证证实了CD-R中粪杆菌和其他产生SCFA的属的减少。基于这些属的分类模型将CD与健康个体区分开,并显示出比使用无关对照鉴定的标记构建的模型更高的诊断能力。此外,这些标记对其他疾病的辨别能力有限.最后,我们的结果在多个队列中得到验证,强调它们的稳健性和诊断和治疗应用的潜力。
    Prior studies indicate no correlation between the gut microbes of healthy first-degree relatives (HFDRs) of patients with Crohn\'s disease (CD) and the development of CD. Here, we utilize HFDRs as controls to examine the microbiota and metabolome in individuals with active (CD-A) and quiescent (CD-R) CD, thereby minimizing the influence of genetic and environmental factors. When compared to non-relative controls, the use of HFDR controls identifies fewer differential taxa. Faecalibacterium, Dorea, and Fusicatenibacter are decreased in CD-R, independent of inflammation, and correlated with fecal short-chain fatty acids (SCFAs). Validation with a large multi-center cohort confirms decreased Faecalibacterium and other SCFA-producing genera in CD-R. Classification models based on these genera distinguish CD from healthy individuals and demonstrate superior diagnostic power than models constructed with markers identified using unrelated controls. Furthermore, these markers exhibited limited discriminatory capabilities for other diseases. Finally, our results are validated across multiple cohorts, underscoring their robustness and potential for diagnostic and therapeutic applications.
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  • 文章类型: Journal Article
    抗性淀粉(RS)的消耗可以对代谢健康产生有益的影响,但是回应,在对肠道微生物群和宿主生理的影响方面,个体之间的差异。预测对RS反应的因素尚未确定,对于开发精确营养方法,最大限度地提高膳食纤维摄入的益处是有用的。我们试图确定肠道微生物群对RS补充反应的预测因子。我们将76名健康成年人纳入一项为期7周的交叉研究,其中59名受试者完成了这项研究。参与者消耗RS类型2(RS2),RS类型4(RS4),和可消化的淀粉,每个10d,中间有5-d的冲洗期。我们在每个治疗期间收集粪便和唾液样本以及食物记录。我们进行了16SrRNA基因测序并测量了粪便短链脂肪酸(SCFA),唾液淀粉酶(AMY1)基因拷贝数,和唾液淀粉酶活性(SAA)。膳食纤维摄入预测了两种RS处理结束时几种扩增子序列变体(ASV)的相对丰度。AMY1相关指标不能预测对RS的反应。SAA仅可预测补充可消化淀粉后一种ASV的相对丰度。有趣的是,SCFA浓度在可消化淀粉补充期间增加最多。处理顺序(RS2和RS4的消耗顺序),阿尔法多样性,一部分ASV可预测补充RS后SCFA的变化。根据我们的发现,如果在推荐补充RS之前进行评估,膳食纤维摄入量和肠道微生物组组成将提供信息,因为这些数据可用于预测特定ASV和粪便SCFA浓度的变化.这些发现为支持以下前提奠定了基础:使用精确营养方法优化RS等膳食纤维的益处可能是一种有效的策略,以补偿全国膳食纤维的低消耗。
    Resistant starch (RS) consumption can have beneficial effects on metabolic health, but the response, in terms of effects on the gut microbiota and host physiology, varies between individuals. Factors predicting the response to RS are not yet established and would be useful for developing precision nutrition approaches that maximize the benefits of dietary fiber intake. We sought to identify predictors of gut microbiota response to RS supplementation. We enrolled 76 healthy adults into a 7-week crossover study with 59 individuals completing the study. Participants consumed RS type 2 (RS2), RS type 4 (RS4), and digestible starch, for 10 d each with 5-d washout periods in between. We collected fecal and saliva samples and food records during each treatment period. We performed 16S rRNA gene sequencing and measured fecal short-chain fatty acids (SCFAs), salivary amylase (AMY1) gene copy number, and salivary amylase activity (SAA). Dietary fiber intake was predictive of the relative abundance of several amplicon sequence variants (ASVs) at the end of both RS treatments. AMY1-related metrics were not predictive of response to RS. SAA was only predictive of the relative abundance of one ASV after digestible starch supplementation. Interestingly, SCFA concentrations increased the most during digestible starch supplementation. Treatment order (the order of consumption of RS2 and RS4), alpha diversity, and a subset of ASVs were predictive of SCFA changes after RS supplementation. Based on our findings, dietary fiber intake and gut microbiome composition would be informative if assessed prior to recommending RS supplementation because these data can be used to predict changes in specific ASVs and fecal SCFA concentrations. These findings lay a foundation to support the premise that using a precision nutrition approach to optimize the benefits of dietary fibers such as RS could be an effective strategy to compensate for the low consumption of dietary fiber nationwide.
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  • 文章类型: Journal Article
    在先前的研究中,姜黄素的一些热降解剂已显示出中等的健康益处。阿魏酸丙酮(FER),最近被确定为姜黄素的热降解剂,以前与抗癌和抗氧化作用有关,然而,它的其他能力仍未被开发。此外,早期的报道表明,芳香环上的甲氧基可能会影响姜黄素的官能团。为了弥补这些差距,进行了一项动物研究,以研究FER及其去甲氧基对应物(DFER)对高脂饮食小鼠的抗肥胖作用.结果表明,两种样品均显著防止了体重增加和肝脏和各种脂肪组织的增大。此外,这些补充剂通过脂联素/AMPK/SIRT1途径在肝脏中表现出脂质调节作用,通过AMPK/PGC-1α激活促进产热,并积极影响肠道微生物产生的短链脂肪酸(SCFA)水平。值得注意的是,DFER在对抗肥胖方面表现出优异的整体疗效,而FER在调节炎症反应方面表现出显著的作用。认为SCFA可能是FER和DFER在动物研究中的不同作用的原因。未来的研究预计将深入研究类姜黄素降解物的功效,包括毒性和药代动力学评估。
    Some thermal degradants of curcuminoids have demonstrated moderate health benefits in previous studies. Feruloyl acetone (FER), recently identified as a thermal degradant of curcumin, has been previously associated with anticancer and antioxidative effects, yet its other capabilities remain unexplored. Moreover, earlier reports suggest that methoxy groups on the aromatic ring may influence the functionality of the curcuminoids. To address these gaps, an animal study was conducted to investigate the antiobesity effects of both FER and its demethoxy counterpart (DFER) on mice subjected to a high-fat diet. The results demonstrated the significant prevention of weight gain and enlargement of the liver and various adipose tissues by both samples. Furthermore, these supplements exhibited a lipid regulatory effect in the liver through the adiponectin/AMPK/SIRT1 pathway, promoted thermogenesis via AMPK/PGC-1α activation, and positively influenced gut-microbial-produced short-chain fatty acid (SCFA) levels. Notably, DFER demonstrated superior overall efficacy in combating obesity, while FER displayed a significant effect in modulating inflammatory responses. It is considered that SCFA may be responsible for the distinct effects of FER and DFER in the animal study. Future studies are anticipated to delve into the efficacy of curcuminoid degradants, encompassing toxicity and pharmacokinetic evaluations.
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  • 文章类型: Journal Article
    非传染性疾病在老龄人口中的日益流行与先天和适应性免疫反应的下降有关;因此,必须确定改善免疫功能的方法,预防相关疾病,减少或治疗与年龄相关的健康并发症。益生元补充剂是调节肠道微生物组和免疫系统的一种有前途的方法,提供了一种潜在的策略来维持老年人免疫功能的完整性。本文综述了细菌代谢产物介导的益生元半乳寡糖(GOS)免疫调节机制的研究进展。包括短链脂肪酸(SCFA)和次级胆汁酸,来维持免疫稳态.还强调了GOS作为免疫疗法在老年人中预防与年龄相关的疾病的潜在应用。这与全球向主动医疗保健的转变相一致,并强调了早期干预在指导个人健康轨迹方面的重要性。重要声明:审查提供了令人信服的证据,证明GOS,作为饮食干预,可以显着增强老年人的肠道健康和免疫调节。基于这些发现,该综述敦促进一步研究,以提高我们对GOS及其潜力的理解,以优化老年人的健康。
    The increasing prevalence of noncommunicable diseases in the aging population has been correlated with a decline in innate and adaptive immune responses; hence, it is imperative to identify approaches to improve immune function, prevent related disorders, and reduce or treat age-associated health complications. Prebiotic supplementation is a promising approach to modulate the gut microbiome and immune system, offering a potential strategy to maintain the integrity of immune function in older individuals. This review summarizes the current research on prebiotic galacto-oligosaccharide (GOS) immunomodulatory mechanisms mediated by bacterial-derived metabolites, including short-chain fatty acids and secondary bile acids, to maintain immune homeostasis. The potential applications of GOS as immunotherapy for age-related disease prevention in older individuals are also highlighted. This aligns with the global shift toward proactive healthcare and emphasizes the significance of early intervention in directing an individual\'s health trajectory.
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  • 文章类型: Journal Article
    在断奶期间,仔猪易发生肠道炎症和屏障功能受损。日粮纤维(DF)在缓解仔猪断奶应激中起着积极作用。然而,不同来源的膳食纤维对断奶仔猪生产性能的影响不一致,以及它们影响肠道健康的机制需要探索。因此,在这项研究中,60头断奶仔猪随机分为三个处理组:基础日粮(对照组,CON),甜菜浆(BP),和苜蓿粉(AM)根据饲料配方进行28天试验。结果表明,AM和BP组均显著降低腹泻率和血清炎症因子(IL-1β和TNF-α),增加抗氧化指标(T-AOC和SOD),除了降低AM组的血清MDA和ROS浓度。同时,AM组的仔猪显示血清肠道通透性指数(LPS和DAO)显着降低,血清免疫球蛋白水平显着增加(IgA,IgG,和IgM)和肠屏障相关基因的表达(Claudin1,Occludin,ZO-1和MUC1),这导致了增长绩效的提高。有趣的是,DF对肠道炎症和屏障功能的影响可归因于其对肠道微生物的调节。富含AM组的纤维降解菌(Christensenellaceae_R-7_组,片球菌和Weissella)通过促进SCFA(尤其是丁酸盐)抑制TLR4-的产生。MyD88-NF-κB信号通路激活减轻肠道炎症,修复肠道屏障功能。总之,为AM缓解断奶应激,改善早期肠功能障碍提供一定的理论支持和依据,这可能对人类婴儿有影响。
    During weaning, piglets are susceptible to intestinal inflammation and impairment in barrier function. Dietary fiber (DF) plays an active role in alleviating weaning stress in piglets. However, the effects of different sources of dietary fiber on the performance of weaned piglets are inconsistent, and the mechanisms through which they affect intestinal health need to be explored. Therefore, in this study, sixty weaned piglets were randomly divided into three treatment groups: basal diet (control, CON), beet pulp (BP), and alfalfa meal (AM) according to the feed formulation for a 28-day trial. The results showed that both AM and BP groups significantly reduced diarrhea rate and serum inflammatory factors (IL-1β and TNF-α) and increased antioxidant markers (T-AOC and SOD), in addition to decreasing serum MDA and ROS concentrations in the AM group. At the same time, piglets in the AM group showed a significant reduction in serum intestinal permeability indices (LPS and DAO) and a substantial increase in serum immunoglobulin levels (IgA, IgG, and IgM) and expression of intestinal barrier-associated genes (Claudin1, Occludin, ZO-1, and MUC1), which resulted in an improved growth performance. Interestingly, the effect of DF on intestinal inflammation and barrier function can be attributed to its modulation of gut microbes. Fiber-degrading bacteria enriched in the AM group (Christensenellaceae_R-7_group, Pediococcus and Weissella) inhibited the production of TLR4- through the promotion of SCFAs (especially butyrate). MyD88-NF-κB signaling pathway activation reduces intestinal inflammation and repairs intestinal barrier function. In conclusion, it may provide some theoretical support and rationale for AM to alleviate weaning stress and improve early intestinal dysfunction, which may have implications for human infants.
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  • 文章类型: Journal Article
    背景:改变肠道代谢产物,特别是短链脂肪酸(SCFA),在帕金森病(PD)患者的粪便和血浆中观察到。
    目的:我们旨在研究两种SCFA受体的结肠表达,游离脂肪酸受体(FFAR)2和FFAR3,与PD患者的肠屏障完整性以及与临床严重程度的相关性。
    方法:在这项回顾性研究中,收集了37例PD患者和34例未受影响的对照组的结肠活检标本.在这个队列中,31名参与者(14名PD,17名对照)接受了一系列结肠活检。通过免疫荧光染色检测FFAR2、FFAR3和紧密连接标记物ZO-1的结肠表达。YouOnlyLookOnce(版本8,YOLOv8)算法用于免疫染色信号的自动检测和分割。使用运动障碍协会(MDS)-统一帕金森病评定量表(UPDRS)评估PD运动功能,便秘采用Rome-IV标准进行评估.
    结果:与对照组相比,PD患者的结肠ZO-1(p<0.01)和FFAR2(p=0.01)表达显着降低。在连续活检中,在PD诊断前的运动前阶段,FFAR2和FFAR3的结肠表达降低(均p<0.01)。MDS-UPDRS运动评分与结肠标志物水平无关。便秘严重程度与结肠ZO-1水平呈负相关(r=-0.49,p=0.02)。
    结论:与未受影响的对照组相比,PD患者中ZO-1和FFAR2的结肠表达较低,在PD运动前阶段,FFAR2和FFAR3水平下降。我们的发现暗示PD中存在漏肠现象,并加强了肠道代谢产物可能有助于PD的过程。
    BACKGROUND: Altered gut metabolites, especially short-chain fatty acids (SCFAs), in feces and plasma are observed in patients with Parkinson\'s disease (PD).
    OBJECTIVE: We aimed to investigate the colonic expression of two SCFA receptors, free fatty acid receptor (FFAR)2 and FFAR3, and gut barrier integrity in patients with PD and correlations with clinical severity.
    METHODS: In this retrospective study, colonic biopsy specimens were collected from 37 PD patients and 34 unaffected controls. Of this cohort, 31 participants (14 PD, 17 controls) underwent a series of colon biopsies. Colonic expression of FFAR2, FFAR3, and the tight junction marker ZO-1 were assayed by immunofluorescence staining. The You Only Look Once (version 8, YOLOv8) algorithm was used for automated detection and segmentation of immunostaining signal. PD motor function was assessed with the Movement Disorder Society (MDS)-Unified Parkinson\'s Disease Rating Scale (UPDRS), and constipation was assessed using Rome-IV criteria.
    RESULTS: Compared with controls, PD patients had significantly lower colonic expression of ZO-1 (p < 0.01) and FFAR2 (p = 0.01). On serial biopsy, colonic expression of FFAR2 and FFAR3 was reduced in the pre-motor stage before PD diagnosis (both p < 0.01). MDS-UPDRS motor scores did not correlate with colonic marker levels. Constipation severity negatively correlated with colonic ZO-1 levels (r = -0.49, p = 0.02).
    CONCLUSIONS: Colonic expression of ZO-1 and FFAR2 is lower in PD patients compared with unaffected controls, and FFAR2 and FFAR3 levels decline in the pre-motor stage of PD. Our findings implicate a leaky gut phenomenon in PD and reinforce that gut metabolites may contribute to the process of PD.
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