Porphyrias

引言通过小分子激活Nrf2是治疗绝经后骨质疏松症的一种很有前途的策略。然而，目前还没有批准用于治疗慢性疾病的Nrf2激活剂，Nrf2调控破骨细胞分化的下游机制尚不清楚。2024年4月2日，华中科技大学李锋及宋科翰共同通讯在Cell Metabolism 在线发表题为“A clinical-stage Nrf2 activator suppresses osteoclast differentiation via the iron-ornithine axis”的研究论文，该研究表明bitopertin，一种临床阶段的甘氨酸摄取抑制剂，通过激活Nrf2抑制破骨细胞分化并改善卵巢切除术诱导的骨质流失。从机制上讲，bitopertin与Keap1 Kelch结构域相互作用，减少Keap1-Nrf2结合，导致Nrf2泛素化和降解减少。在小鼠和人类受试者中，与临床批准的Nrf2激活剂相比，Bitopertin与更少的不良事件相关。此外，Nrf2转录激活铁转运蛋白编码基因Slc40a1，以降低破骨细胞内的铁水平。Nrf2缺失或补铁上调鸟氨酸代谢酶Odc1，从而降低鸟氨酸水平，从而促进破骨细胞分化。总之，该研究确定了一种新的临床阶段Nrf2激活剂，并提出了破骨细胞中一种新的Nrf2-铁-鸟氨酸代谢轴。绝经后骨质疏松症是在缺乏雌激素的情况下由破骨细胞过度活化引起的代谢紊乱。骨密度(BMD)的降低使患者髋部或椎体脆性骨折的风险增加，在全球范围内造成严重的残疾和社会经济负担破骨细胞在巨噬细胞集落刺激因子(M-CSF)和核因子kB配体受体激活剂(RANKL)的刺激下向骨髓源性巨噬细胞(bmdm)分化。用双膦酸盐化合物靶向破骨细胞是治疗骨质疏松症的主流策略。然而，严重的不良反应和较差的依从性是许多患者标准化双膦酸盐治疗的障碍，导致骨质疏松症治疗不足需要发现新的治疗靶点，以确保对这些患者提供更好的护理。核因子E2相关因子2 (Nrf2)是一种氧化还原相关的转录因子，其激活可通过抑制破骨细胞分化来改善绝经后骨质疏松症。在非胁迫条件下，Nrf2被Keap1隔离在细胞质中，并被Cul3泛素连接酶泛素化，用于蛋白酶体降解在氧化应激过程中，Nrf2与Keap1分离并易位到细胞核，激活多种参与细胞抗氧化反应的细胞保护基因。这些基因的Nrf2结合位点被称为抗氧化反应元件(AREs)由于具有细胞保护作用，已经发现了许多Nrf2激活因子。然而，它们中的大多数是亲电性和间接Nrf2激活剂，共价靶向KEAP1中的半胱氨酸151，其中只有两种被批准用于临床使用，即延胡索酸二甲酯(DMF)用于治疗复发型多发性硬化症和omaveloxolone (OMA)用于治疗弗里德赖希共济失调。除Keap1外，这些亲电Nrf2激活因子还与其他关键酶或蛋白质的半胱氨酸残基相互作用并影响其功能，导致“脱靶”和毒性作用。在人类中，在临床试验中，间接Nrf2激活剂与高不良事件发生率相关另一种策略是找到Keap1-Nrf2相互作用的直接抑制剂来选择性激活Nrf2。然而，直接Nrf2激活剂通常分子大小较大，这降低了其进入中枢神经系统治疗相关疾病的能力，目前尚无临床批准的直接Nrf2激活剂。因此，开发更安全、更有效的Nrf2激活剂用于临床仍然是一个挑战。模式图（Credit: Cell Metabolism）Bitopertin是一种口服、临床甘氨酸转运蛋白1 (Glyt1)抑制剂，最初用于治疗精神分裂症。最近，bitopertin被FDA授予孤儿药资格，用于治疗红细胞生成性卟啉原症(EPP)，这是一种罕见的、使人衰弱的、潜在威胁生命的血液疾病。bitopertin治疗EPP的疗效正在两项正在进行的2期临床试验AURORA (NCT05308472)和BEACON (ACTRN12622000799752)中进行评估bitopertin的潜在临床应用是基于其限制甘氨酸摄取的作用。有趣的是，骨质疏松症患者的血清甘氨酸水平明显高于骨密度正常的患者。另一项研究显示，甘氨酸支持谷胱甘肽的形成，并有助于脂多糖刺激后BMDMs中白细胞介素(IL)-1β的产生，表明甘氨酸具有促炎作用。然而，目前尚不清楚甘氨酸水平升高是否与骨质疏松症有因果关系，以及甘氨酸是否影响BMDMs向破骨细胞的分化。该研究发现bitopertin，而不是甘氨酸补充剂，通过Nrf2激活改善卵巢切除术(OVX)诱导的骨质疏松症。在机制上，bitopertin与Kelch结构域相互作用，减少Keap1-Nrf2相互作用，减少Nrf2降解。与现有的临床Nrf2激活剂相比，Bitoeprtin在人类受试者中更安全，与更少的不良事件相关。更重要的是，该研究发现了一个新的Nrf2 -铁-鸟氨酸代谢轴在破骨细胞分化。该研究结果表明，bitopertin在治疗骨质疏松症中具有先前未被认识到的治疗作用，并有助于阐明Nrf2对破骨细胞作用的分子机制。原文链接https://www.cell.com/cell-metabolism/abstract/S1550-4131(24)00084-6责编|探索君排版|探索君文章来源|“iNature”End往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文Nature | 破除传统：为何我们需要重新思考肿瘤的命名方式热文Nature | 2024年值得关注的七项技术热文Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文CRISPR技术进化史 | 24年Cell综述

Met primary endpoint, demonstrating dose-dependent, statistically significant reductions in protoporphyrin IX (PPIX) compared to placebo in both 20 mg and 60 mg dose groupsImproved measures of light tolerance, including the key secondary endpoint, in both 20 mg and 60 mg dose groups, but did not meet statistical significance compared to placeboDose-dependent reductions in the rate of phototoxic reactions with pain, with statistical significance at the 60 mg dose group compared to placeboDose-dependent improvements in the Patient Global Impression of Change (PGIC), with statistical significance at the 60 mg dose group compared to placeboInvestor webcast at 8:30 am ET to discuss top-line data WATERTOWN, Mass., April 01, 2024 (GLOBE NEWSWIRE) -- Disc Medicine, Inc. (NASDAQ:IRON), a clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of novel treatments for patients suffering from serious hematologic diseases, today presented topline data from AURORA, a phase 2 study of bitopertin in patients with EPP. Treatment with bitopertin resulted in statistically significant reductions in PPIX, the primary endpoint, and significant improvements in the rate of phototoxic reactions with pain and the Patient Global Impression of Change (PGIC). On the key secondary endpoint of cumulative time in sunlight on days without pain, bitopertin patients had a positive response consistent with BEACON results, but the endpoint did not meet statistical significance due to strong placebo performance. “This study has confirmed that bitopertin significantly reduces the toxic metabolite, PPIX, in patients with EPP, and we have shown that bitopertin-treated patients experience improvements in the clinically meaningful outcomes of Patient Global Impression of Change and the number and rate of phototoxic reactions with pain, with the 60 mg dose reaching statistical significance compared to placebo. Despite the strong performance of bitopertin on the key secondary endpoint of cumulative time in light, consistent with results seen in BEACON, statistical significance was not met due to an outsized placebo response,” said John Quisel, J.D., Ph.D., President and Chief Executive Officer. “Given that, we will need to conduct an analysis of our final data set and work with investigators, regulators, and patient advocacy groups to define the optimal registrational endpoints moving forward. While we do this additional work, we continue to be excited about the upcoming readouts from our other programs, including updated data from our DISC-0974 study in anemia of myelofibrosis in Q2.” The AURORA study is a randomized, double-blind, placebo-controlled phase 2 study that enrolled 75 adult subjects with EPP. Subjects were randomized 1:1:1 to receive 20 mg of bitopertin, 60 mg of bitopertin, or placebo once daily for 17 weeks. Summary of topline results Primary endpoint Bitopertin resulted in significant, dose-dependent, and sustained reductions in whole blood PPIX levels: -21.6% for 20 mg (p=0.003 vs placebo) and -40.7% for 60 mg (p<0.001 vs placebo); the placebo group had mean increases of +8.0% Secondary endpoints Cumulative total time in sunlight between 10 am and 6 pm on days without pain observed over the 4-month treatment period: bitopertin-treated patients recorded a mean of 175.1 hours at 20 mg and 153.1 hours at 60 mg, compared with 133.9 hours for placebo; results were not statistically significant compared to placebo The magnitude of the improvement in the bitopertin-treated patients was comparable to that observed in the BEACON study, but the benefit in the placebo arm in the AURORA trial was greater than expected Large improvements in light tolerance from baseline in 20 mg and 60 mg bitopertin treatment groups as measured by time to prodrome; results were not statistically significant relative to placebo.Substantial and dose-dependent reductions in phototoxic reactions with pain during the 4-month study period: 75% reduction in the incidence rate of new phototoxic reactions with pain at the 60 mg dose group compared to placebo (p=0.011); 60% reduction in the 20 mg dose group (p=0.109)Fewer bitopertin-treated patients reported a phototoxic event compared to placebo: 19% for 20 mg and 12% for 60 mg compared to 46% for placebo Dose-dependent improvements in PGIC, which were statistically significant for the 60 mg dose: 77% of completers at 20 mg and 86% at 60 mg (p=0.022 vs placebo) reported that their EPP was “much better” compared with 50% for placeboBitopertin was generally well tolerated in both dose groups with no serious adverse events and stable hemoglobin levels. Two patients discontinued treatment due to treatment-emergent AEs, both in the 60 mg dose group: one due to dizziness and one due to a skin rash. The most common AE reported with bitopertin treatment was dizziness: n=4 in the 20 mg dose group, n=11 in the 60 mg dose group compared with n=4 in the placebo group (median durations of 4.5, 5, and 2 days, respectively) Webcast Conference Call InformationManagement will host a call on Monday, April 1 at 8:30 am ET to review the data. Please register for management’s webcast on the Events and Presentations page of Disc’s website (https://ir.discmedicine.com/). About BitopertinBitopertin is an investigational, clinical-stage, orally-administered inhibitor of glycine transporter 1 (GlyT1) that is designed to modulate heme biosynthesis. GlyT1 is a membrane transporter expressed on developing red blood cells and is required to supply sufficient glycine for heme biosynthesis and support erythropoiesis. Disc is planning to develop bitopertin as a potential treatment for a range of hematologic diseases including erythropoietic porphyrias, where it has potential to be the first disease-modifying therapy. There are currently two ongoing phase 2 clinical trials of bitopertin in patients with EPP that have fully enrolled and have had key data readouts: the open-label trial called BEACON and a randomized, double-blind placebo-controlled trial called AURORA. Bitopertin is an investigational agent and is not approved for use as a therapy in any jurisdiction worldwide. Disc obtained global rights to bitopertin under a license agreement from Roche in May 2021. About Erythropoietic Protoporphyria (EPP) and X-linked Protoporphyria (XLP)Erythropoietic protoporphyria (EPP) and X-linked Protoporphyria (XLP) are rare, debilitating and potentially life-threatening diseases caused by mutations that affect heme biosynthesis, resulting in the accumulation of a toxic, photoactive intermediate called protoporphyrin IX (PPIX). This causes severe reactions when patients are exposed to sunlight, characterized by excruciating pain, edema, burning sensations and potential blistering and disfigurement. PPIX also accumulates in the hepatobiliary system and can result in complications including gallstones, cholestasis, and liver damage in 20-30% of patients and in extreme cases liver failure. Current standard of care involves extreme measures to avoid sunlight, including restricting outdoor activities to nighttime, use of protective clothing and opaque shields, and pain management. This has a significant impact on the psychosocial development, quality of life, and daily activities of patients, particularly in young children and families. There is currently no cure for EPP and only one FDA-approved therapy, a surgically implanted synthetic hormone designed to stimulate melanin production called Scenesse® (afamelanotide). About Disc MedicineDisc Medicine is a clinical-stage biopharmaceutical company committed to discovering, developing, and commercializing novel treatments for patients who suffer from serious hematologic diseases. We are building a portfolio of innovative, potentially first-in-class therapeutic candidates that aim to address a wide spectrum of hematologic diseases by targeting fundamental biological pathways of red blood cell biology, specifically heme biosynthesis and iron homeostasis. For more information, please visit www.discmedicine.com. Disc Medicine Cautionary Statement Regarding Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, express or implied statements regarding Disc’s expectations with respect to its BEACON Phase 2 clinical studies of bitopertin and projected timelines for the initiation and completion of its clinical trials and other activities. The use of words such as, but not limited to, “believe,” “expect,” “estimate,” “project,” “intend,” “future,” “potential,” “continue,” “may,” “might,” “plan,” “will,” “should,” “seek,” “anticipate,” or “could” or the negative of these terms and other similar words or expressions that are intended to identify forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on Disc’s current beliefs, expectations and assumptions regarding the future of Disc’s business, future plans and strategies, clinical results and other future conditions. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Disc may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and investors should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements as a result of a number of material risks and uncertainties including but not limited to: the adequacy of Disc’s capital to support its future operations and its ability to successfully initiate and complete clinical trials; the nature, strategy and focus of Disc; the difficulty in predicting the time and cost of development of Disc’s product candidates; Disc’s plans to research, develop and commercialize its current and future product candidates; the timing of initiation of Disc’s planned preclinical studies and clinical trials; the timing of the availability of data from Disc’s clinical trials; Disc’s ability to identify additional product candidates with significant commercial potential and to expand its pipeline in hematological diseases; the timing and anticipated results of Disc’s preclinical studies and clinical trials and the risk that the results of Disc’s preclinical studies and clinical trials may not be predictive of future results in connection with future studies or clinical trials and may not support further development and marketing approval; the other risks and uncertainties described in the “Risk Factors” section of our Annual Report on Form 10-K for the year ended December 31, 2023 and other documents filed by Disc from time to time with the Securities and Exchange Commission (SEC), as well as discussions of potential risks, uncertainties, and other important factors in Disc’s subsequent filings with the SEC. Any forward-looking statement speaks only as of the date on which it was made. None of Disc, nor its affiliates, advisors or representatives, undertake any obligation to publicly update or revise any forward-looking statement, whether as result of new information, future events or otherwise, except as required by law. Media Contact Peg RusconiVerge Scientific Communicationsprusconi@vergescientific.com Investor Relations Contact Christina TartagliaStern Investor Relationschristina.tartaglia@sternir.com

03月29日的《热心肠日报》，我们解读了 15 篇文献，关注：超加工食品，IBS，膳食碳水化合物，致病菌定植，口腔菌，益生菌，饮食-菌群互作，知易生物，BMS，Endostart，新光维医疗，农夫山泉。 ​​ 该篇日报由R·AI辅助创作生成，人工审核校对。 设计更加健康和可持续的超加工食品（综述） Comprehensive Reviews in Food Science and Food Safety——[14.8] ① 本综述描述了超加工食品（UPFs）的概念、与慢性疾病之间的关联以及改善其健康性和可持续性的潜在策略；② 文章指出UPFs的消费与肥胖、糖尿病等慢性疾病有关，原因包括挤占了整体食物摄入、高能量密度、缺乏植物化学物、包装化学物质污染、过度可口、有害添加剂、消化吸收快以及存在有毒反应产物；③ 此外，文章提出了减少能量密度、平衡营养成分、强化营养、增加饱腹感、调节咀嚼和消化特性、重新设计食物结构和精准加工等改进UPFs的策略；④ 尽管需要通过严格的科学研究来证明这些改进策略的有效性，但文章认为改良和重新设计许多UPFs以提高其健康性和可持续性是可能的。 【原文信息】 designing healthier and more sustainable ultraprocessed foods 2024-03-22 , doi: 10.1111/1541-4337.13331 摄入过多超加工食品增加肠易激综合征风险 Clinical Gastroenterology and Hepatology——[12.6] ① 首都医科大学附属北京友谊医院朱圣韬与团队发表前瞻性队列研究，探讨了超加工食品消费与肠易激综合征（IBS）长期患病风险之间的关联；② 本研究纳入17万余参与者，他们平均超加工食品消耗量为总饮食的21.0%，在平均随访11.3年中，共发现2690例新发IBS病例；③ 每增加10%的超加工食品消费，IBS的风险增加8%；④ 与超加工食品消费最低四分位数相比，最高四分位数的消费者患IBS的风险增加19%；⑤ 本研究结果表明，较高的UPFs消费量与IBS事件风险增加有关，并具有显著的剂量反应关系。 【原文信息】 Ultra-Processed Food Consumption and Long-Term Risk of Irritable Bowel Syndrome: A Large-Scale Prospective Cohort Study 2024-03-21 , doi: 10.1016/j.cgh.2024.01.040 膳食碳水化合物调节肺炎克雷伯菌的肠道定植和播散 Journal of Clinical Investigation——[15.9] ① 肺炎克雷伯菌是存在于上呼吸道和胃肠道的条件致病菌，缺乏膳食纤维的配方饮食（如全肠内营养）促进人类受试者肠道中肺炎克雷伯菌的生长；② 在小鼠模型中，膳食纤维可提高小鼠肠道微生物多样性，进而抑制肺炎克雷伯菌的定植；③ 此外，膳食纤维可减轻肠炎并减少肺炎克雷伯菌播散到血液和肝脏；④ 碳源（简单碳水化合物）而非氮源是肺炎克雷伯菌在小鼠肠道中定植的主要限制因素；⑤ 膳食简单和复杂碳水化合物对肺炎克雷伯菌的肠道定植和传播具有关键作用，简单碳水化合物（如乳果糖）可促进其生长，而复杂碳水化合物（如膳食纤维）则可抑制其定植，针对膳食干预可能为预防高风险患者肺炎克雷伯菌感染提供策略。 【原文信息】 Dietary carbohydrates regulate intestinal colonization and dissemination of Klebsiella pneumoniae 2024-03-21 , doi: 10.1172/JCI174726 Lancet子刊：金黄色葡萄球菌的定植和去定植（综述） Lancet Microbe——[38.2] ① 金黄色葡萄球菌是导致人类感染相关死亡的主要原因之一，由于其对抗生素的广泛耐药性，预防金黄色葡萄球菌感染的关键策略是去定植；② 金黄色葡萄球菌的主要定植部位包括鼻咽部、肠道、皮肤等，肠道可能是主要的定植部位和储存库；③ 去定植策略包括使用抗生素和抗菌剂，但存在争议和缺陷，包括耐药性的产生和破坏正常菌群；④ 一些新的去定植策略正在研究中，包括使用特定的噬菌体、细菌素和益生菌，这些策略更加特异，对正常菌群的影响较小；⑤ 尽管金黄色葡萄球菌被认为是人体正常菌群的一部分，但其定植与感染风险增加相关，去定植对预防感染有一定效果，但相关策略仍需改进。 【原文信息】 Staphylococcus aureus colonisation and strategies for decolonisation 2024-03-19 , doi: 10.1016/S2666-5247(24)00040-5 口腔牙龈卟啉单胞菌加速胰腺癌发展 Gut——[24.5] ① 牙龈卟啉单胞菌可从小鼠口腔迁移到胰腺，并在人类胰腺内上皮内瘤病变中检测到；② 反复给予野生型C57BL/6小鼠牙龈卟啉单胞菌可诱导胰腺腺泡-导管化生（ADM），并改变胰腺内微生物组成；③ 在Kras突变小鼠中，牙龈卟啉单胞菌加速了胰腺内上皮内瘤向胰腺导管腺癌的进展；④ 在体外实验中，牙龈卟啉单胞菌感染诱导了腺泡细胞ADM标记物SOX9和CK19的表达，并且细胞内牙龈卟啉单胞菌保护胰腺导管腺癌细胞免受营养应激引起的活性氧化物的细胞死亡；⑤ CXCR4是牙龈卟啉单胞菌在胰腺导管腺癌细胞上的受体。 【原文信息】 Oral bacteria accelerate pancreatic cancer development in mice 2024-01-17 , doi: 10.1136/gutjnl-2023-330941 华南理工大学：益生菌发酵草药-功能性食品的新宠（综述） Comprehensive Reviews in Food Science and Food Safety——[14.8] ① 药食同源（Medicine Food Homology，MFH）是指一些食物本身也是药物，研究表明许多MFH可以通过肠道菌群的转化而产生生物活性，因此益生菌发酵MFH成了研究的热点，华南理工大学吴虹团队发表综述对该领域进行了探讨；② 在益生菌发酵MFH（如丁香、肉桂、罗汉果等）的过程中，其代谢会改变MFH，增加其活性成分、降解毒素和抗营养因子并改善其风味；③ 而MFH为益生菌的生长提供了物质基础，促进了其代谢产物的产生；④ 益生菌发酵MFH具有抗菌、抗氧化、抗炎、抗神经退行性疾病、皮肤保护和调节肠道微生物组的健康益处；⑤ 但同时由于MFH来自经济作物，会受到杀虫剂和化肥的污染，而益生菌发酵过程则可能产生霉菌毒素。 【原文信息】 Probiotic-fermented edible herbs as functional foods: A review of current status, challenges, and strategies 2024-02-20 , doi: 10.1111/1541-4337.13305 东南大学：益生菌的肠道输送新进展（综述） Advanced Materials——[29.4] ① 近期东南大学生物科学与医学工程学院吴富根团队发表综述，总结了肠道传递益生菌的材料、策略和应用，重点讨论了益生菌包埋策略的进展和工程益生菌的治疗应用；② 肠道传递益生菌面临存活和定植问题，采用生物膜、脂质、纳米涂层等方法封装益生菌可提高其在肠道中的存活率；③ 合成生物学的进展为高效、有目的地设计和操纵益生菌创造了新机会；④ 当前益生菌肠道递送仍存在一些挑战，如益生菌种类选择、封装材料安全性、评价体系不完善等，未来需要加强益生菌基因组学研究，开发高效安全的递送系统，以推动益生菌在临床上的应用。 【原文信息】 Intestinal Delivery of Probiotics: Materials, Strategies, and Applications 2024-01-21 , doi: 10.1002/adma.202310174 “益生菌城市”：一种更健康的城市生态系统 Trends in Biotechnology——[17.3] ① 本文探讨了微生物科学与整合生物设计相结合，旨在通过创建“益生菌城市”来应对城市生态系统退化和人类疾病的挑战；② 接种枯草芽孢杆菌的新型陶瓷和混凝土材料，可以限制建筑环境中抗菌素耐药性的传播，而接种沙箱等城市材料可以支持免疫调节；③ 微生物接种剂促进生物多样性和生态系统，在绿色屋顶、蜜蜂益生菌、城市林业和生物修复应用中战略性地使用微生物接种剂，可以打造更健康、更有弹性的城市生态系统；④ 生物集成材料具有对抗超级细菌和修复污染的潜力，而在景观材料中接种微生物群可以促进人体免疫调节和生物多样性绿色基础设施，打造“益生菌城市”。 【原文信息】 Probiotic Cities: microbiome-integrated design for healthy urban ecosystems 2024-02-16 , doi: 10.1016/j.tibtech.2024.01.005 短期补充蔓越莓提取物对人体肠菌有何影响？ NPJ Biofilms and Microbiomes——[9.2] ① 通过充分表征市售蔓越莓提取物的酚类和寡糖含量，并评估其对28名人类受试者肠道微生物群的影响；② 仅四天后，富含酚和寡糖的蔓越莓提取物就诱导出强烈的双歧杆菌作用，同时增加了几种产生丁酸盐的细菌（例如梭菌属和Anaerobutyricum）的丰度；③ 蔓越莓提取物也会导致血浆和粪便中短链脂肪酸比例的变化，表现为乙酸比例下降，而丁酸比例上升；④ 基于肠菌变化将受试者分层，发现具有普氏菌属特征的个体在补充蔓越莓提取物后粪杆菌属的增加尤为显著。 【原文信息】 Short term supplementation with cranberry extract modulates gut microbiota in human and displays a bifidogenic effect 2024-03-06 , doi: 10.1038/s41522-024-00493-w 肠道菌群的暂时变异与饮食模式间有何关联？ American Journal of Clinical Nutrition——[7.1] ① 纳入444名参与者，通过一年期观察发现特定饮食模式与肠道菌群的多样性变化相关；② 识别到91个细菌属的时间内类相关系数（ICC）大于0.5，表明这些细菌在一年内具有相对稳定的存在；③ 识别出以拟杆菌属、普氏菌属和瘤胃菌科为主导的三个细菌群，这些群体的饮食指数遵循度不同；④ 高度遵循北欧、地中海和植物性饮食模式的人群，其肠道中富含多种纤维降解特性的细菌，而那些与不良健康结果相关的细菌丰度较低；⑤ 结果表明，特定的饮食习惯可以显著影响肠道微生物组成，为通过饮食改善肠道健康提供了依据。 【原文信息】 Temporal gut microbiota variability and association with dietary patterns: from the one-year observational DCH-NG MAX study 2024-01-30 , doi: 10.1016/j.ajcnut.2024.01.027 活菌药公司「知易生物」完成近亿元C轮首期融资 ① 近日，广州知易生物宣布完成了近亿元人民币C轮首期融资，本轮融资由粤科金融领投、爱瑞投资跟投；② 融资主要用于推进知易生物活菌药物SK08的3期临床试验开发；③ SK08是国内进展最快的活菌药物，用于治疗腹泻型肠易激综合征（IBS- D）；④ 此外，公司另一项用于化疗相关性腹泻的原创品种SK10，其美国1期临床也已完成。 【原文信息】 知易生物完成近亿元C轮首期融资，加速临床 III期管线推进 2024-03-28 , 知易生物 BMS Opdivo+Yervoy组合一线治疗结直肠癌获优先审评 ① 3月27日，国家药监局药品审评中心官网显示，百时美施贵宝（BMS）的纳武利尤单抗（Opdivo）+伊匹木单抗（Yervoy）双重免疫治疗组合拟纳入优先审批；② 该组合用于一线治疗不可切除或转移性微卫星高度不稳定性（MSI-H）或错配修复缺陷型（dMMR）结直肠癌（CRC）患者；③ CheckMate-8HW研究结果显示，该组合可使患者疾病进展或死亡风险降低79%；④ Opdivo+Yervoy的安全性与之前数据一致，可控且无新的安全信号。 【原文信息】 Opdivo+Yervoy组合拟优先审评，一线治疗结直肠癌 2024-03-27 , 医药魔方Info Endostart磁导航球囊产品Endorail获得FDA批准 ① 近日，Endostart公司宣布，旗下磁导航球囊产品Endorail获得FDA 510（k）许可；② 在肠镜检查或者肠镜手术过程中，结直肠会存在挠曲或环结现象，肠镜一般很难通过环结区域；③ Endorail可辅助肠镜通过环结区域，快速完成结直肠诊断或者治疗，从而提高结肠镜检查的效率和安全性；④ 2023年，Endostart公司在多地进行的临床试验证实，Endorail在完成困难结肠镜检查中具有高安全性和有效性。 【原文信息】 Endostart receives FDA clearance for Endorail product to optimise colonoscopy procedural outcomes 2024-03-27 , Med-Tech 新光维医疗宣布与波士顿科学达成战略合作 ① 近日，新光维医疗科技（苏州）股份有限公司（简称“新光维医疗”）宣布与医疗科技公司波士顿科学正式签署战略合作协议；② 根据协议，双方将合作开发新一代内窥镜产品，以及将产品在全球范围内进行商业化推广；③ 据弗若斯特沙利文统计，预计到2030年全球一次性使用医用内窥镜市场规模将增至92亿美元；④ 此次合作将加速新光维医疗的全球化步伐，为全球提供更全面的一次性使用内窥镜整体解决方案。 【原文信息】 新光维医疗与波士顿科学再次携手并深化战略合作 2024-03-26 , 新光维医疗 农夫山泉投资千万成立农业公司 ① 3月25日，农夫山泉宣布投资成立杭州雅叶农业发展有限公司，注册资本为1000万人民币；② 公司由钟睒睒担任执行董事，饶明红为法定代表人兼经理；③ 经营范围涵盖茶叶制品生产、初级农产品收购、发酵技术研发等；④ 该公司由农夫山泉全资子公司浙江农夫实业发展有限公司全资持股。 【原文信息】 农夫山泉投资千万成立农业公司 2024-03-27 , FoodTalks 感谢本期日报的审核者：注册营养师陈彬林，RZN，好雨，九卿臣，Richard，lxx 点击阅读过去10天的日报： 0328 | Science子刊：锁定肠道中让病毒逃脱免疫的"避风港" 0327 | 10文聚焦菌群-肠-脑轴研究新进展 0326 | 100分综述详解：IBD细胞因子疗法最前沿 0325 | 大肠癌患病为何年轻化？遗传与生活方式的双重影响 0324 | 大型临床试验：补钙补D如何影响老年女性长期健康？ 0323 | Lancet+JAMA领衔，聚焦炎症性肠病诊断与治疗 0322 | 陈豪燕/洪洁等Cell子刊：免疫治疗对老年人更有效，肠道菌群或是隐藏功臣 0321 | 今日Nature双发：促肠癌菌和宿主-菌群互作研究均有新突破 0320 | 12页高分综述解析：抗生素扰乱菌群，对宿主代谢有何影响？ 0319 | 今日Cell：国内团队发现新肠道激素，连起肠肝轴胆固醇代谢调控