Branch chain amino acids vs. Rifaximin in patients with cirrhosis for secondary prophylaxis of hepatic encephalopathy: Double blind placebo controlled multicentric randomised controlled trial. - HERB Trial

开始日期2026-06-29

申办/合作机构

Mankind Pharma Ltd.

NCT07180615

/ Not yet recruiting临床4期IIT

Neomycine/Metronidazole- vs Rifaximin-based Gut Decolonisation Prior to Colon Surgery: a Randomized Multicenter Trial

The goal of this clinical trial is to find out if a gut cleaning using Rifaximin works as well as the usual treatment with Neomycin and Metronidazole to prevent infections after colon surgery. The study includes adult patients who will have colon surgery.
The main question it aims to answer are:
-Does the Rifaximin treatment prevent surgical site infections as well as the Neomycin/Metronidazole treatment?
Other things the study will look at:
* How often infections happen, stratified on how deep they are, the type of surgery the patients got, or if bowel cleaning was done before surgery.
* How many people will die after surgery
* How long people stay in hospital
Participants will:
* Take either Rifaximin or Neomycin/Metronidazole one day before surgery to clean their gut
* Keep a diary until the surgery to record medication intake and any side effects
* Be contacted by phone 30 days after surgery to ask about their condition and any side effects,

开始日期2026-06-01

申办/合作机构

Universität Luzern

NCT07683936

/ Recruiting早期临床1期IIT

A Prospective Exploratory Study on Fecal Microbiota Transplantation for the Treatment of Refractory Hepatic Encephalopathy After TIPS Surgery

This is a single-center, prospective, open-label, parallel-group exploratory clinical study designed to evaluate the safety and preliminary efficacy of fecal microbiota transplantation combined with standard medical therapy in patients with refractory overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt. The study also aims to explore whether adjunctive prebiotic supplementation may improve clinical outcomes and support gut microbiota reconstruction after fecal microbiota transplantation.
A total of 26 participants with recurrent overt hepatic encephalopathy after TIPS despite standard therapy with rifaximin and lactulose will be enrolled. All participants will continue to receive standard medical therapy, including rifaximin and lactulose. During an episode of overt hepatic encephalopathy, all participants will receive fecal microbiota transplantation via a nasojejunal tube at a dose of 100 mL per administration, twice daily, for 3 consecutive days. Participants will be assigned in a 1:1 ratio to either the fecal microbiota transplantation group or the fecal microbiota transplantation plus prebiotic group. Participants in the combination group will receive dietary fiber prebiotic supplementation at 24 g/day for 4 weeks in addition to the same fecal microbiota transplantation and standard medical therapy.
Participants will be followed for up to 6 months. The primary efficacy assessment will focus on recurrence of hepatic encephalopathy, including recurrence rate, time to first recurrence, episode grade, and duration. Secondary assessments will include time to reversal of hepatic encephalopathy, West Haven grade, blood ammonia, liver and kidney function, inflammatory markers, liver function scores, neurocognitive function, and changes in gut microbiota composition. Safety assessments will include adverse events, fecal microbiota transplantation-related adverse events, infection, worsening hepatic encephalopathy, hospitalization, and serious adverse events. This study is expected to provide preliminary clinical evidence for a microbiota-based therapeutic strategy in patients with refractory overt hepatic encephalopathy after TIPS.

开始日期2026-06-01

申办/合作机构-

100 项与利福昔明相关的临床结果

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100 项与利福昔明相关的转化医学

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100 项与利福昔明相关的专利（医药）

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1,711

项与利福昔明相关的文献（医药）

2026-12-31·Gut Microbes

Muribaculum as a microbial contributor of rifaximin-induced mucosal protection during chemotherapy

Article

作者: Rescigno, Maria ; Gatti, Andrea ; Lizier, Michela ; Algieri, Francesca ; Braga, Daniele ; Carloni, Sara ; De Zanet, Stefano ; Brescia, Paola ; Morandi, Martina ; Correale, Carmen ; Spinelli, Antonino ; Rossetti, Riccardo ; Penna, Giuseppe ; Gil-Gomez, Antonio ; Maroli, Annalisa ; Foppa, Caterina ; Silvestri, Alessandra

Chemotherapy-induced intestinal mucositis is a frequent and dose-limiting toxicity that compromises cancer treatment outcomes and lacks effective targeted interventions. Here, we investigate the mechanisms by which the nonabsorbable antibiotic rifaximin mitigates chemotherapy-induced intestinal injury, focusing on microbiota-mediated preservation of epithelial barrier integrity. In a murine model of 5-fluorouracil (5-FU)-induced intestinal injury, rifaximin pretreatment reduced mucosal inflammation and tissue damage, preserved epithelial and mucus barrier integrity, and limited systemic endotoxemia. Importantly, rifaximin did not impair the antitumor efficacy of 5-FU in Apc^Min/+C3arKO mice. To assess translational relevance, we employed a human intestinal ex vivo organ culture system (EVOC) and found that rifaximin preserved mucosal architecture, mucus balance, and tight junction integrity following inflammatory challenge. Microbiome profiling revealed that rifaximin reshaped the intestinal microbial community, preventing the depletion of health-associated taxa, including Muribaculum and Parasutterella. Functional experiments demonstrated that Muribaculum intestinale supplementation alone attenuated 5-FU-induced injury, reproducing key protective features of rifaximin treatment. Together, these findings identify Muribaculum as a microbial contributor to rifaximin's protective effects, supporting its potential role as a safe adjunctive strategy to improve gastrointestinal tolerability of cancer treatment.

2026-08-01·AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY

Microbiota dysbiosis and mucosal hyperinnervation contribute to intestinal hyperalgesia in a mouse model of postinfectious irritable bowel syndrome

Article

作者: Yu, Linda Chia-Hui ; Hsin, Ling-Wei ; Tu, Chia-Hung ; Lin, Yu-Hsuan ; Wu, Ming-Shiang ; Kuo, Wei-Ting ; Sun, Chin-Hung ; Lin, Li-Yu

A mouse model of postinfectious IBS was developed using dual triggers of Giardia postinfection and water avoidance stress to mimic diverse risk factors. Rifaximin treatment reduced intestinal hyperalgesia and was associated with decreased mucosal neurite outgrowth and brain-derived neurotrophic factor (BDNF) expression. BDNF activation induced nerve fiber elongation and upregulated 5-HT 7 expression via separate signaling pathways. Analgesic combinations of RFX and a 5-HT 7 receptor antagonist reduced intestinal nociception to baseline.

2026-08-01·ALIMENTARY PHARMACOLOGY & THERAPEUTICS

Rifaximin Improves Cognitive Performance and Reduces Cirrhosis‐Related Adverse Events in Covert Hepatic Encephalopathy: A Randomized Controlled Trial

Article

作者: Tanaka, Yasuhito ; Yoshimaru, Yoko ; Shimizu, Masahito ; Tanaka, Kentaro ; Watanabe, Takehisa ; Mizuta, Takahiro ; Nakayama, Jiro ; Miwa, Takao ; Nagaoka, Katsuya ; Maeda, Daiki ; Toyota, Toshinori ; Sugi, Kazuhiro ; Kurano, Sotaro ; Uojima, Haruki ; Iio, Etsuko ; Narahara, Satoshi ; Inada, Hiroki ; Iwasaki, Shuichiro ; Miyase, Shiho ; Hidaka, Hisashi ; Setoyama, Hiroko ; Miuma, Satoshi

ABSTRACT:

Background:

Covert hepatic encephalopathy (CHE) is associated with cognitive impairment and adverse clinical outcomes; however, randomized evidence supporting therapeutic intervention remains limited.

Aim:

To evaluate the efficacy of rifaximin (RFX) as a treatment for CHE.

Methods:

In this multicentre, open‐label randomized controlled trial, patients with CHE associated with liver cirrhosis were randomized (1:1) to receive RFX or no treatment and followed for 12 weeks. The primary endpoint was the change in Stroop test performance. Secondary endpoints included NCT‐B scores, serum ammonia levels, cirrhosis‐related adverse events, and gut microbiota composition.

Results:

Fifty patients were randomized and completed follow‐up. Stroop test performance improved significantly in the RFX group ( p = 0.006) but not in controls ( p = 0.400), with a trend toward greater improvement with RFX (Δ Stroop test: −4.45 ± 7.12 vs. −0.98 ± 5.74 s; p = 0.056). Among patients not receiving synthetic disaccharides at baseline, improvement was significantly greater with RFX (Δ Stroop test: −3.73 ± 5.96 vs. −0.80 ± 5.86 s; p = 0.049). No significant changes were observed in NCT‐B scores or serum ammonia levels. Cirrhosis‐related adverse events were significantly reduced in the RFX group ( p = 0.006). Overall, gut microbial diversity did not differ between groups; however, RFX selectively altered specific taxa, including loss of the [Eubacterium] brachy group.

Conclusions:

RFX improved cognitive performance assessed by the Stroop test and reduced cirrhosis‐related adverse events in patients with CHE. These randomized data support RFX as an effective therapeutic option and highlight the Stroop test as a sensitive endpoint for treatment response.

265

项与利福昔明相关的新闻（医药）

2026-08-17

·北京医学感染与传染研究

柳叶刀·胃肠病学与肝病学 11卷 7-9期

THE LANCET Gastroenterology & Hepatology. Volume 11Number7 柳叶刀·胃肠病学与肝病学 11卷 7期 https://www.thelancet.com/journals/langas/issue/current Editorial（社论） 1 Rome V: refining the language of gut–brain disorders 罗马Ⅴ：完善肠–脑疾病的术语体系 The Lancet Gastroenterology & Hepatology The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p541 Comment（述评） 2 A changing HIV treatment landscape: what does lenacapavir mean for people living with HBV? HIV治疗格局之变：来那卡帕韦对HBV感染者意味着什么？ Philippa C Matthews,Marion Delphin,Motswedi Anderson,Joanna Redmond,Stuart Flanagan,Maryam Shahmanesh The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p542 3 Alaska Native peoples and colorectal cancer: opportunities for research and prevention 阿拉斯加原住民与结直肠癌：研究与预防的机遇 Diana Redwood,LaRita Laktonen-Ward,Elena Roik The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p544 4 Breaking the cycle: from documenting data scarcity to enabling global IBD research 打破循环：从记录数据匮乏到推动全球IBD研究 Mohammed Nabil Quraishi,Badr Al-Bawardy,Rupa Banerjee,Maiara Brusco De Freitas,David Epstein,Tine Jess The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p546 Correspondence（读者来信） 5 Cyclic exclusive enteral nutrition in paediatric Crohn's disease 儿童克罗恩病的周期性全肠内营养 Aaron S Bancil,Edward M Giles,Jessica Fitzpatrick The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p550 6 Cyclic exclusive enteral nutrition in paediatric Crohn's disease – Authors’ reply 儿童克罗恩病的周期性全肠内营养——作者回复 Bénédicte Pigneur,Frank M Ruemmele The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p550 7 Upfront medical or surgical treatment in Crohn's disease 克罗恩病的初始药物治疗还是手术治疗 Nurulamin M Noor,Phillip R Fleshner,Gil Y Melmed,Corey A Siegel The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p551 8 Upfront medical or surgical treatment in Crohn's disease – Authors’ reply 克罗恩病的初始药物治疗还是手术治疗——作者回复 Lotte Oldenburg,Anouck E G Haanappel,Geert R D’Haens,Willem A Bemelman The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p552 9 Cirrhotic cardiomyopathy and portal hypertension: addressing the full disease spectrum in heart–liver co-management 肝硬化心肌病与门静脉高压：在心–肝协同治疗中关注完整疾病谱 Madeleine Gill,Geoffrey W McCaughan,Anoop N Koshy,John F O’Sullivan,Avik Majumdar The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p553 Corrections（勘误） 10 Correction to Lancet Gastroenterol Hepatol 2026; 11: 355–66 勘误：柳叶刀·胃肠病学与肝病学 2026; 11: 355–66 The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：e9 11 Correction to Lancet Gastroenterol Hepatol 2026; 11: 557–69 勘误：柳叶刀·胃肠病学与肝病学 2026; 11: 557–69 The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：e9 News（新闻） 12 Digestive Disease Week 2026 2026年消化疾病周 Bethany Gomersall The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p555 In Focus（焦点） Theatre（剧场） 13 Wee, Poo, Snot: harnessing bodily functions to inspire budding scientists 尿液、粪便、鼻涕：利用身体功能激发未来科学家的兴趣 Peter Ranscombe The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p556 Articles（论著） 14 Adjuvant chemoradiotherapy versus completion total mesorectal excision after local excision for early rectal cancer (TESAR): a multicentre, randomised, controlled, phase 3, non-inferiority trial 辅助放化疗与局部切除后完全全直肠系膜切除术治疗早期直肠癌（TESAR）：一项多中心、随机、对照、3期、非劣效性试验 Laura R Moolenaar,Mahsoem Ali,Theo J Aufenacker,Geerard L Beets,Robbert J I Bosker,Tineke E Buffart,Jacobus WA Burger,Evelien Dekker,Quentin Denost,Pascal G Doornebosch,Peter van Duijvendijk,Hans F J Fabry,Elisabeth D Geijsen,Michael F Gerhards,Wilhelmina M U van Grevenstein,Brechtje A Grotenhuis,Christiaan Hoff,Jeroen W A Leijtens,Koen C M J Peeters,Apollo Pronk,George P van der Schelling,Colin Sietses,Anke B Smits,Boudewijn R Toorenvliet,Anthony W H van de Ven,Emiel G G Verdaasdonk,Ronald J C L M Vuylsteke,Henderik L van Westreenen,Johannes H W de Wilt,David D E Zimmerman,Marilyne M Lange,Nicole C T van Grieken,Barbara A J Bastiaansen,Roel Hompes,Corrie A Marijnen,Marcel G W Dijkgraaf,Leon M G Moons,Pieter J Tanis,Chris Cunningham,J B Tuynmanon behalf of the TESAR Study Group The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p557 15 Effect of one or two cycles of dual immunotherapy with nivolumab and ipilimumab in patients with mismatch repair-deficient rectal cancer (RESET-R): interim results from a multicentre, single-arm, phase 2 trial 纳武利尤单抗联合伊匹木单抗双免疫治疗一或两个周期对错配修复缺陷型直肠癌患者的疗效（RESET-R）：一项多中心、单臂、2期试验的中期结果 Line Schmidt Tarpgaard,Laurids Østergaard Poulsen,Ismail Gögenur,Tobias Freyberg Justesen,Søren Rafael Rafaelsen,Nadia Øgaard,Christina Demuth,Claus Lindbjerg Andersen,Lise Ventzel,Pernille Øhlenschläger Larsen,Anne Ramlov,Ken Ljungmann,Michael Bødker Lauritzen,Laura Vittrup Diness,Jakob Lykke,Vinicius Araújo Barbosa de Lima,Søren Kjær,Søren Salomon,Per Vadgaard Andersen,Per Pfeiffer The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p570 16 The small interfering RNA imdusiran as single and multiple doses in healthy, randomised individuals and non-randomised individuals with chronic hepatitis B (AB-729–001): a phase 1a/b trial 小干扰RNA imdusiran（药物名称）在健康随机个体及慢性乙型肝炎非随机个体中单次及多次给药的研究（AB-729–001）：一项1a/b期试验 Man-Fung Yuen,Edward Gane,Jacinta A Holmes,Simone I Strasser,Apinya Leerapun,Wattana Sukeepaisarnjaroen,Pisit Tangkijvanich,Elina Berliba,Alina Jucov,Yoon Jun Kim,Young-Suk Lim,Emily P Thi,Timothy Eley,Kevin R Gray,Elina Medvedeva,Varun Sharma,Christine Espiritu,Sharie C Ganchua,Bhavna S Paratala,Christina Iott,Heather Sevinsky,Tiffany Fortney,Mark Anderson,Gavin A Cloherty,Michael J Sofia,Ganapati Reddy Pamulapati,Amy C H Lee,Gastón Picchio,Karen D Sims The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p579 17 Intestinal ultrasound to detect postoperative recurrence in patients with Crohn's disease: an international, multidisciplinary, RAND/UCLA appropriateness method study 肠道超声检测克罗恩病术后复发：一项国际多学科RAND/UCLA适宜性方法研究 Christopher Ma,Siwar Albashir,Mariangela Allocca,Anthony de Buck van Overstraeten,Paulo G Kotze,Cathy Lu,Christian Maaser,Giovanni Maconi,Remo Panaccione,Miguel Regueiro,Jordi Rimola,Antonino Spinelli,Stuart A Taylor,Rune Wilkens,Willem Bemelman,Noa Krugliak Cleveland,Krisztina B Gecse,Susan Archer,Soushyant Kiarasi,Linda J Cornfield,Kerri L Novak The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p602 Review（综述） 18 The use of pharmacotherapies in non-cirrhotic metabolic dysfunction-associated steatohepatitis: a UK expert consensus 非肝硬化代谢功能障碍相关脂肪性肝炎的药物治疗：英国专家共识 Jeremy F Cobbold,Hamish Miller,Kate Hallsworth,Pinelopi Manousou,Thomas Marjot,Michael E D Allison,Quentin M Anstee,Matthew J Armstrong,Leah Avery,Vian Azzu,Paul N Brennan,Christopher D Byrne,Tessa M Cacciottolo,Lynsey Corless,Daniel Forton,Timothy Hardy,Vanessa Hebditch,Helen Jarvis,Wenhao Li,Dina Mansour,Stuart McPherson,Yensiew Miao,Joanne Morling,Ashis Mukhopadhya,Benjamin Mullish,Richard Parker,Imran Patanwala,Jay Patel,Michael Pavlides,Tina Reinson,Ian A Rowe,Francesca Saffioti,Faisal Shaikh,Ankur Srivastava,Nwe Ni Than,Emmanuel Tsochatzis,Edvard Volcek,Jeremy W Tomlinson,William Alazawi The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p616 19 Management of colorectal cancer in older adults: an expert panel recommendation to guide daily clinical practice 老年结直肠癌的治疗：指导日常临床实践的专家组建议 Gabor Liposits,Thierry André,Thomas Aparicio,Isacco Montroni,Julien Taieb,Claire Gallois,Eric Van Cutsem,Michel Ducreux,Per Pfeiffer,Sara Lonardi,Geerard L Beets,Karin Haustermans,Naureen Starling,Gerald W Prager,Gunnar Folprecht,Demetris Papamichael The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p627 THE LANCET Gastroenterology & Hepatology. Volume 11Number 8 柳叶刀·胃肠病学与肝病学 11卷 8期 https://www.thelancet.com/journals/langas/issue/current Editorial（社论） 1 Drugging the undruggable in pancreatic cancer 攻克胰腺癌中“不可成药”靶点的药物研发 The Lancet Gastroenterology & Hepatology The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p645 Comment（述评） 2 Effect of repeated elastography measurements in LiverScreen 肝脏筛查项目中重复弹性检测的临床价值 Hannes Hagström,Ying Shang The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p646 3 Metabolic syndrome myopathy: defining an emerging clinical entity in patients with MASLD 代谢综合征肌病：代谢相关脂肪性肝病患者一类新兴临床疾病的确立 Melinda Wang,Jennifer C Lai The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p647 4 All in her head: dismantling medical misogyny in disorders of gut–brain interaction 一切皆源于主观臆症：破除肠脑互动疾病诊疗中的医学厌女偏见 Tiffany H Taft,Tina Aswani-Omprakash,Johannah Ruddy The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p650 Correspondence（读者来信） 5 COLOR III: widespread TaTME dissemination demands a LAPCO-equivalent framework COLOR III研究：经肛全直肠系膜切除术广泛推广亟需建立等同腹腔镜结直肠手术协作组的规范体系 Shazad Q Ashraf,Andrew D Beggs The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p653 6 The spectrum of steatotic liver disease in the USA 美国脂肪性肝病疾病谱 Kartik Jaidka,Naveen Bhagat,Arka De,Ajay Duseja The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p653 7 The spectrum of steatotic liver disease in the USA 美国脂肪性肝病疾病谱 Hans Scherübl The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p654 8 The spectrum of steatotic liver disease in the USA – Authors’ reply 《美国脂肪性肝病疾病谱》——作者答复 James M Paik,Zobair M Younossi The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p655 9 Lessons from a ransomware crisis and its effect on adult liver transplant services 勒索软件网络危机及其对成人肝移植诊疗服务的影响与启示 Abdul Rahman Hakeem,Karen Mercer,Bu Hayee,Oliver Long,Abid Suddle,Wayel Jassem,Parthi Srinivasan,Krishna Menon,Anneliese Rigby,Miriam Cortes-Cerisuelo,Varuna Aluvihare The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p655 Corrections（勘误） 10 Correction to Lancet Gastroenterol Hepatol 2025; 10: 998–1012 《柳叶刀-胃肠病学与肝病学》2025年第10卷998–1012页文章勘误 The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：e10 11 Correction to Lancet Gastroenterol Hepatol 2026; 11: 546–49 《柳叶刀-胃肠病学与肝病学》2026年第11卷546–549页文章勘误 The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：e10 News（新闻资讯） 12 EASL Congress 2026 2026年欧洲肝脏研究协会年会 Rob Brierley The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p658 13 Research in Brief 研究简讯 Holly Baker The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p659 Articles（论著） 14 HLA-DRB1*01:03 in patients with inflammatory bowel disease: a genotype–phenotype association study 炎症性肠病患者HLA-DRB1*01:03基因型：基因型-表型关联研究 Qian Zhang,Eathar Shakweh,Mohmmed Tauseef Sharip,Benjamin Zare,Christopher Roberts,Nicola J Wyatt,Jennifer Clough,Claire Bewshea,Omar El Garwany,Robert Lees,Saima Mukhtar,Hameed Rehman,Hollie Thistle,Robert Mulligan,Melanie Taylor,Parizade Raymode,Benjamin Hamilton,Nurulamin M Noor,Francesco Morda,Madeleine Taylor,Mina Gyanwali,Ogwa Tobi,Stefanos Kateroglou,Sean Von Hagt,UK IBD Genetics Consortium,NIHR IBD BioResource,Shaji Sebastian,Ailsa Hart,Laura Keylock,Laetitia Pele,Charlie W Lees,Tim Raine,Christopher A Lamb,Carl A Anderson,Tariq Ahmad,Holm Uhlig,Miles Parkes,Laura Fachal,Nicholas A Kennedy,James C Lee The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p660 15 Dupilumab versus placebo in adults and adolescents with eosinophilic gastritis (DEGAS): a double-blind, placebo-controlled, phase 2, multicentre, randomised controlled trial 度普利尤单抗对比安慰剂治疗成人及青少年嗜酸性粒细胞性胃炎（DEGAS研究）：一项Ⅱ期、双盲、安慰剂对照、多中心随机对照临床试验 Nirmala P Gonsalves,Evan S Dellon,Kara L Kliewer,Tetsuo Shoda,Regina Yearout,Seema S Aceves,Nicoleta C Arva,John A Besse,Julie M Caldwell,Mirna Chehade,Amaziah Coleman,Margaret H Collins,Sara Anvari,Gary W Falk,Sandeep K Gupta,Girish Hiremath,David A Katzka,Paneez Khoury,John Leung,Calies Menard-Katcher,Paul Menard-Katcher,Kathryn A Peterson,Maria A Pletneva,Amanda K Rudman Spergel,Jonathan M Spergel,Tatyana Vaysman,Joshua B Wechsler,Benjamin L Wright,Guang-Yu Yang,Xue Zhang,Meijian Zhou,Ashish Bansal,Bram P Raphael,Amr Radwan,Jennifer Maloney,Antonio Martin,Yamo Deniz,Glenn T Furuta,Lisa J Martin,Marc E Rothenbergfor The Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) Investigators The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p672 16 Liver stiffness dynamics in European populations (LiverScreen): a longitudinal, multicentre, prospective, population-based cohort study 欧洲人群肝脏硬度动态变化研究（肝脏筛查项目）：一项基于人群、多中心、前瞻性纵向队列研究 Jesse Pustjens,Katrine Tholstrup Bech,Guillem Pera,Laurens A van Kleef,Helle Lindholm Schnefeld,Robert J de Knegt,Sarwa Darwish Murad,Harry L A Janssen,Peter Andersen,Johanne Kragh Hansen,Llorenç Caballeria,Carla Chacon,Ingrid Arteaga,Pere Toran,Anita Arslanow,Anna Soria,Marta Cervera,Aleksander Krag,Isabel Graupera,Pere Ginès,Willem Pieter Brouwer,Maja Thieleon behalf of the LiverScreen Consortium Investigators The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p689 17 Addition of ipilimumab to atezolizumab plus bevacizumab in advanced hepatocellular carcinoma (PRODIGE 81-FFCD 2101-TRIPLET HCC): phase 2 results from a randomised, multicentre, open-label, phase 2–3 trial 阿替利珠单抗联合贝伐珠单抗基础上加用伊匹木单抗治疗晚期肝细胞癌（PRODIGE 81-FFCD 2101-TRIPLET HCC研究）：一项多中心、开放标签Ⅱ/Ⅲ期随机临床试验Ⅱ期研究结果 Philippe Merle,Jean-Frederic Blanc,Karine Le Malicot,Jean-Marie Peron,Vincent Bourgeois,Mohamed Bouattour,Yann Touchefeu,Carole Vitellius,Faiza Khemissa Akouz,Alexandra Heurgué,Paul Girot,Eric Assenat,Eric Nguyen-Khac,Jean-Pierre Bronowicki,Juliette Viaud,Meher Ben Abdelghani,Sylvain Manfredi,Julien Edeline,Jean-Marc Phelipfor the TRIPLET-HCC study investigators The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p700 Viewpoint（观点） 18 Breaking the therapeutic ceiling in inflammatory bowel disease: myth or reality? 突破炎症性肠病治疗瓶颈：空想还是现实？ Virginia Solitano,Vipul Jairath,Fernando Magro,Alessandro Armuzzi,Laurent Peyrin-Biroulet,Silvio Danese The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p713 19 Balancing benefit and burden: rethinking post-polypectomy colonoscopy surveillance strategies 权衡获益与医疗负担：重新思考息肉切除术后结肠镜随访监测策略 Joep E G IJspeert,Michael Bretthauer,Rodrigo Jover,Evelien Dekkeron behalf of the Dutch colonoscopy surveillance working group The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p720 THE LANCET Gastroenterology & Hepatology. Volume 11Number 9 柳叶刀·胃肠病学与肝病学 11卷 9期 https://www.thelancet.com/journals/langas/issue/current Editorial（社论） 1 A decade in gastroenterology and hepatology 胃肠病学与肝病学十年回顾 The Lancet Gastroenterology & Hepatology The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p727 Comment（评述） 2 Low‑dose aspirin: effective cancer chemoprevention in Lynch syndrome 低剂量阿司匹林：林奇综合征有效的癌症化学预防方案 Kevin J Monahan The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p728 3 RELIEVE UCCD: one pathway, two diseases, and a glimpse into the future of IBD trial design RELIEVE‑UCCD研究：同一条通路、两类疾病，窥探炎症性肠病临床试验设计的未来方向 Bram Verstockt The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p729 4 Combination therapy in metabolic dysfunction‑associated steatohepatitis 代谢功能障碍相关脂肪性肝炎的联合治疗 Oren Shibolet,Helena Katchman The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p732 5 The central role of primary care in liver health 基层医疗在肝脏健康管理中的核心作用 Rob Brierley,Hugh Thomas The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p733 6 A decade in inflammatory bowel disease: progress, plateaus, and perspectives 炎症性肠病十年发展：进展、瓶颈与展望 Britta Siegmund The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p735 7 A decade of transformation in MASLD: from nomenclature to novel therapies 代谢功能障碍相关脂肪性肝病十年变革：从命名更新到新型疗法 Jörn M Schattenberg,Mazen Noureddin The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p737 8 Dietary management of gastrointestinal disease: progress over the last decade and opportunities for the next 胃肠道疾病的膳食干预：近十年进展与未来机遇 Kevin Whelan,Heidi M Staudacher The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p738 9 The decade that changed hepatocellular carcinoma: shaping a new treatment paradigm 改写肝细胞癌诊疗格局的十年：构建全新治疗模式 Antonio D’Alessio,Antonella Cammarota,Stephen L Chan,Lorenza Rimassa The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p741 10 Ten years of advances in disorders of gut–brain interaction 肠‑脑互动相关疾病十年研究进展 Alexander C Ford,Nicholas J Talley The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p743 11 Progress and prospects in viral hepatitis elimination 病毒性肝炎消除工作的进展与前景 C Wendy Spearman,Mark W Sonderup The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p745 12 A decade of progress in cholestatic liver diseases: navigating a new era 胆汁淤积性肝病十年进展：迈入全新发展阶段 Vincenzo Ronca,Maria Buzias,Ana Lleo The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p748 13 Translating the gut microbiome: where are we? 肠道微生物组的临床转化：当下发展现状 Jeroen Raes The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p750 14 A decade of artificial intelligence in endoscopy: from proof of concept to clinical reality 人工智能内镜应用十年：从概念验证走向临床落地 Masashi Misawa,Yuichi Mori The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p752 15 A decade of diversity, equity, and inclusion in gastroenterology and hepatology: a US perspective 胃肠肝病领域多元、公平与包容建设十年——美国视角 Pascale M White,Nikki Duong,Laura E Targownik,Sophie Balzora The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p754 Correspondence（通信） 16 Therapeutic drift or formulation drift: avoiding misconceptions about rifaximin and antimicrobial resistance in cirrhosis 药效偏移还是制剂差异：厘清肝硬化患者利福昔明与抗菌耐药性的认知误区 Carmelo Scarpignato,Manuel Romero‑Gómez The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p757 17 Therapeutic drift or formulation drift: avoiding misconceptions about rifaximin and antimicrobial resistance in cirrhosis –Authors' reply 药效偏移还是制剂差异：厘清肝硬化患者利福昔明与抗菌耐药性的认知误区——作者回复 Rajiv Jalan,Vishal C Patel,Saeed Shoaie The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p758 18 Ethnicity, diversity, and inclusion in gastroenterology: from representation to system performance 胃肠病学领域种族、多元与包容建设：从人员覆盖到体系效能 Ajay M Verma,Debbie L Shawcross,Neeraj Bhala The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p758 Articles（论著） 19 Aspirin for cancer prevention in individuals with Lynch syndrome: first results from the CaPP3 multicentre, randomised, double‑blind, non‑inferiority trial 阿司匹林用于林奇综合征人群癌症预防：CaPP3多中心随机双盲非劣效性试验初步结果 John Burn,Gillian M Borthwick,Faye Elliott,Finlay Macrae,Kai Ren Ong,Alison C Kraus,Nadir Arber,Jukka‑Pekka Mecklin,Angel Alonso,Emma R Woodward,D Gareth Evans,Alex Murray,Katie Snape,Ruth E Cleaver,Adam Shaw,Huw J W Thomas,Ajith V Kumar,Dorothy Halliday,Lucy E Side,Rachel E Harrison,Rosemarie Davidson,Ruth Armstrong,Jackie Cook,Rachel Hart,Patrick J Morrison,Julian G Barwell,Alan Donaldson,Zoe Kemp,Jennie Murray,Zosia Miedzybrodzka,Caroline Pottinger,Jonathan Berg,Richard Gallon,D Timothy Bishopon behalf of the CaPP3 co‑investigators The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p760 20 Efficacy and safety of duvakitug in patients with ulcerative colitis (RELIEVE UCCD): a phase 2b, randomised, placebo‑controlled trial Duvakitug治疗溃疡性结肠炎的疗效与安全性（RELIEVE‑UCCD）：2b期随机安慰剂对照试验 Walter Reinisch,David Stepek,Radoslaw Kempinski,Silvio Danese,Bruce E Sands,Bogdan Ratiu‑Duma,Rajendra Singh,Phillip Levine,Hadas Barkay,Nicholas Gross,Ken Abrams,Vipul Jairath The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p775 21 Efficacy and safety of duvakitug in patients with Crohn's disease (RELIEVE UCCD): a phase 2b, randomised, placebo‑controlled trial Duvakitug治疗克罗恩病的疗效与安全性（RELIEVE‑UCCD）：2b期随机安慰剂对照试验 Vipul Jairath,Jaroslaw Kierkuś,George Aaron Duvall,Silvio Danese,Bruce E Sands,Bogdan Ratiu‑Duma,Rajendra Singh,Phillip Levine,Hadas Barkay,Nicholas Gross,Ken Abrams,Walter Reinisch The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p786 22 Efficacy and safety of zalfermin co‑administered with semaglutide in participants with fibrosis and cirrhosis due to metabolic dysfunction‑associated steatohepatitis: a phase 2, dose‑ranging, double‑blind, randomised controlled trial 扎弗明联合司美格鲁肽治疗代谢相关脂肪性肝炎所致肝纤维化与肝硬化受试者的疗效及安全性：2期剂量探索双盲随机对照试验 Rohit Loomba,Jacob George,Laurent Castera,Sven Francque,Eric Lawitz,Ahsan Shoeb,Jesper Ole Clausen,Birgitte Andersen,Anna Bille Larsen,Lise Lotte Gluud The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p797 23 The Rome V criteria for the diagnosis of irritable bowel syndrome in secondary care: a diagnostic accuracy study 二级医疗机构中罗马V标准诊断肠易激综合征的诊断准确度研究 Kyle Staller,Vivek C Goodory,Mais Khasawneh,Christopher J Black,Alexander C Ford The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p812 The Lancet Gastroenterology & Hepatology Commission（《柳叶刀‑胃肠病学和肝病学》专题委员会报告） 24 The role of primary care in response to the global liver disease syndemic: a Lancet Gastroenterology & Hepatology Commission 基层医疗应对全球肝病共病流行的作用——《柳叶刀‑胃肠病学和肝病学》专题委员会报告 Helen Jarvis,Paul N Brennan,Teresa Casanovas,Kelly Casler,Monica Desai,Philip H Evans,John F Dillon,Ignazio Grattagliano,Kate Hallsworth,Vanessa Hebditch,Sema Mandal,Alisa E Pedrana,Jen‑Kuei Peng,Andrew D Schreiner,Abdel‑Aziz Shaheen,Maja Thiele,Patricia C Valery,Julia Verne,Shlomo Vinker,David Whiteley,Martin C S Wong,Shira Zelber‑Sagi The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p821

2026-08-16

·小包子学演化

Science Bulletin｜利用肠道微生物组管理 MASLD：机遇与挑战

引言代谢功能障碍相关脂肪性肝病(MASLD)既往称为非酒精性脂肪性肝病(NAFLD)，是一组广泛存在且患病率持续上升的肝脏疾病谱，其特征为在无显著饮酒的情况下肝脏脂肪过度蓄积。MASLD 与肥胖、2 型糖尿病、高血压和血脂异常等代谢合并症密切相关，目前影响全球超过 30% 的成年人口，且在青少年与年轻成人中呈令人担忧的上升态势。作为一种进展性疾病，MASLD 可由单纯性肝脂肪变逐步进展为代谢功能障碍相关脂肪性肝炎(MASH)、肝纤维化、肝硬化，并最终演变为肝细胞癌，因而在全球范围内造成日益加重的临床与社会经济负担。近年来微生物组学的进展已确立肠-肝轴作为疾病发生与进展的关键调节因子。肠道微生物组成、功能潜能与代谢活性的改变会破坏肠道稳态，并促进可直接影响肝脏生理的系统炎症信号。微生物来源的代谢物，包括次级胆汁酸与支链氨基酸(BCAA)，进一步通过受体介导的通路影响肝脏脂质代谢、胰岛素敏感性与炎症信号。这些认识凸显了基于微生物组的生物标志物与疗法在改善 MASLD 诊断、预防与治疗方面的价值。在正常状态下，肠道微生物群通过调节黏膜结构、紧密连接蛋白、免疫教育以及短链脂肪酸(SCFA)和其他生物活性代谢物的产生来维持肠道完整性。然而在 MASLD 中，这种平衡被显著失调所打破，表现为微生物多样性降低并转向促炎类群。变形菌门(Proteobacteria)与肠杆菌科(Enterobacteriaceae)的扩增，伴随有益厚壁菌门(Firmicutes)与拟杆菌门(Bacteroidetes)成员的减少，会削弱上皮屏障完整性并增加肠道通透性。其结果是，脂多糖(LPS)等病原相关分子模式(PAMPs)更容易易位进入门静脉循环。LPS 与肝脏库普弗细胞上的 Toll 样受体 4(TLR4)结合，激活 NF-κB 依赖的炎症级联反应并促进促炎细胞因子产生。这种炎症微环境导致肝细胞损伤并促进肝星状细胞活化，推动纤维化进展。微生物失调还会引起显著的代谢紊乱，进一步加剧 MASLD 病理。次级胆汁酸(如脱氧胆酸(DCA))浓度升高以及循环 BCAA 增加，会损害法尼醇 X 受体(FXR)与 Takeda G 蛋白偶联受体 5(TGR5)信号，加剧肝脏脂质蓄积并降低胰岛素敏感性。产乙醇肠杆菌科的过度增殖增加内源性乙醇生成，促进肝细胞的氧化应激、脂质过氧化与线粒体功能障碍。性别特异的微生物特征(如女性中 Christensenella 丰度更高)也可能促成内脏脂肪量与炎症基调的异质性。通过这些相互关联的代谢与免疫机制，肠道失调成为 MASLD 疾病进展的核心放大因素。除细菌失调外，日益增多的多组学证据表明，MASLD 还伴随肠道生态系统内的跨界改变，涉及真菌(真菌组)、病毒(病毒组/噬菌体组)与古菌。临床研究报道肠道真菌负荷增加，尤以念珠菌属(Candida)富集为著，同时噬菌体群体扩增，可能优先靶向有益的共生菌。产甲烷古菌的改变亦被提出，并可能与肠道屏障完整性受损及促炎微生物产物经门静脉递送增强相关。总体而言，这些非细菌组分会与细菌失调相互作用，进一步增加肠-肝轴紊乱的复杂性，并促进 MASLD 中的肝脏炎症与代谢功能障碍。图1：益生菌疗法用于 MASLD 的当前局限与应对策略。肠道微生物组调控：MASLD 的潜在治疗策略基于上述机制认识，调控肠道微生物生态系统已成为 MASLD 颇具前景的治疗策略。在现有方法中，益生菌补充(尤其是含鼠李糖乳杆菌(Lactobacillus rhamnosus)或长双歧杆菌(Bifidobacterium longum)的制剂)仍是最广泛采用的手段，并已显示有助于恢复微生物平衡、支持上皮屏障功能并调节宿主免疫反应。2025 年一项荟萃分析报道，含双歧杆菌(Bifidobacterium)的益生菌可改善胰岛素敏感性、降低甘油三酯并升高高密度脂蛋白(HDL)胆固醇，凸显其潜在的代谢益处。菊粉与低聚果糖等益生元可进一步增强微生物发酵能力与短链脂肪酸(SCFA)产生，与益生菌联用为合生元时可能产生叠加效应。一致地，2024 年一项纳入 28 项随机对照试验(RCT)的网络荟萃分析发现，合生元补充可改善肝酶、肝脏脂肪变与炎症标志物。除单菌株益生菌与合生元外，由乳杆菌属(Lactobacillus)、双歧杆菌属(Bifidobacterium)及其他细菌类群组成的多菌株制剂在 MASLD 中引起越来越大的兴趣。这些组合与短链脂肪酸产生增强、上皮屏障完整性改善相关，并在肝酶、脂肪变与炎症参数方面表现出更显著的改善。然而，主要国际指南(EASL-EASD-EASO 2024/2025；AASLD 2025)目前仍将益生菌、益生元与合生元视为 MASLD 中的研究性干预，反映出其在纤维化或肝脏组织学持久改善方面证据有限。益生菌疗法当前面临的局限尽管取得上述进展，若干局限仍制约着益生菌疗法的更广泛应用(见图1)。一项关键挑战是益生菌制剂的表征与报告不一致。不同的乳杆菌(Lactobacillus)菌株可通过不同机制调节肝脏炎症、胆汁酸信号、胰岛素敏感性或脂肪酸氧化，然而许多研究遗漏了必要的菌株水平细节，如登录号、基因组特征、培养条件、活力评估或剂量标准化。弥补这些缺口需要采用标准化报告框架，例如《益生菌研究最低信息》(MIPS)指南，并配合储存基因组与功能注释的集中化菌株库，以实现对菌株特异性效应的可重复评估。另一主要局限是动物模型在再现人类 MASLD 多因素病理生理方面的保真度不足。广泛使用的饮食与化学模型，如高脂饮食(HFD)、蛋氨酸-胆碱缺乏(MCD)喂养或四氯化碳(CCl4)损伤，可再现肝脂肪变或纤维化等孤立特征，却无法捕获其整合的代谢、免疫与微生物复杂性。遗传模型(包括 ob/ob 与 db/db 小鼠)纳入了肥胖与胰岛素抵抗，但代表的是极端的单基因缺陷，难以反映人类多基因疾病。这些局限，叠加物种间胆汁酸谱、免疫架构与微生物-宿主互作的特异性差异，导致临床前研究中益生菌疗效与临床试验结果之间频繁脱节。例如，一项针对 MASLD 患者的随机对照试验显示，合生元补充改变了粪便微生物组组成，但未能降低经 MRI 质子密度脂肪分数(MRI-PDFF)评估的肝脏脂肪含量，亦未改善纤维化相关标志物。这种不一致凸显了一个关键转化挑战：微生物组调控未必能转化为人类 MASLD 中肝脏脂肪变或纤维化的可测量改善。为提升转化相关性，将 HFD 与代谢或微生物应激源结合的新型多重打击(multi-hit)模型能更好地模拟人类疾病轨迹，而人源化平台(如将人类微生物群移植至无菌小鼠)有助于保留关键的宿主-微生物互作。配套技术——包括成分明确的微生物组合、基于 CRISPR 的共生菌操控、多组学整合、肝脏类器官与微流控肝芯片(liver-on-chip)系统——提供了机制深度与更具生理相关性的平台。当前的益生菌干预还主要局限于第一代菌株，如乳杆菌属(Lactobacillus)与双歧杆菌属(Bifidobacterium)，其通过定植与竞争排斥发挥广泛、非特异性的效应。相比之下，下一代益生菌(NGP)——包括产孢细菌、基因工程菌株或被设计用于递送靶向效应分子(如抗炎细胞因子或胆汁酸调节剂)的微生物——有望实现精准、机制驱动的干预，针对纤维化或代谢失调等病理生理特征。然而，其开发与临床转化面临显著壁垒，包括针对基因修饰生物的严格法规、长期安全性担忧、人体试验中的伦理复杂性，以及可规模化生产的局限。建立针对天然来源与工程化活体生物疗法的分级监管框架，包括一个可能得到基因组安全性审计支持的定制微生物制剂类别，可加速开发与临床采纳。另一局限是 MASLD 益生菌研究缺乏长期随访。多数试验周期短(8–24周)，聚焦于肝酶或血脂水平等即时生化改善，而未评估纤维化消退或肝硬化预防等具有临床意义的结局。小样本量进一步限制了按疾病分期、合并症或代谢表型进行的亚组分析，可能高估获益并遗漏罕见不良事件。未来研究应纳入更长的随访期、规模更大且更多样的队列，并在应用标准化微生物组报告框架的同时，对遗传背景、脂质代谢与体脂分布等宿主因素进行深度表型分析。这些措施将支持可重复性、厘清应答者特征，并推动益生菌干预向精准、机制驱动的治疗迈进。超越益生菌：微生物组导向的强化干预除益生菌外，更为强化的微生物组导向方法提供了额外的治疗潜力。来自严格筛选供体的粪便微生物群移植(FMT)可实现肠道微生物群更深、更持久的重塑，抑制有害类群并促进健康菌群谱的形成。饮食干预——尤其是地中海饮食(MedDiet)——亦发挥显著的微生物组介导益处。其高纤维、多酚与抗氧化成分可富集阿克曼菌属(Akkermansia)与罗氏菌属(Roseburia)等有益类群，降低内毒素血症并减轻肝脏炎症。药物疗法进一步补充这些方法。例如，不可吸收的抗生素利福昔明可减少小肠细菌过度增殖并降低内毒素暴露，而胰高血糖素样肽-1(GLP-1)受体激动剂(如司美格鲁肽)可改善代谢稳态并将微生物组成转向更平衡的状态。展望展望未来，以精准微生物组为中心的方法不仅有望补充 MASLD 管理，更有望革新代谢性肝病的诊断、预防与治疗。然而，必须应对若干重大挑战，包括微生物组应答的个体间差异、监管不确定性、工程化微生物的长期安全性担忧、可规模化生产的局限，以及许多试验过度依赖短期替代终点而非持久临床结局。克服这些障碍对于实现微生物组疗法的潜力并确立对临床转化的合理预期至关重要。一条清晰的推进路径是，将机制认识与下一代益生菌、微生物组靶向的饮食与药物干预以及严格的临床评价相整合。通过将高分辨率微生物组谱与患者的特异性代谢和遗传数据相结合，可针对个体疾病表型定制疗法，在最大化疗效的同时最小化风险。实现这些目标将取决于进一步发展具有人类相关性的实验模型、厘清工程化微生物疗法的监管框架，以及开展长期的、具有充分把握度的临床试验，从而将这些策略有效地从实验室推向临床。作者： Wu Bao, Gaopeng Li, Yuan Ding, Yuhao Wang

2026-08-16

·肠道菌群新功能

工程菌：从“被动吃药”到“智能响应”的活体药物时代

当细菌被改造成“智能传感器”，疾病治疗正在迎来一场静默的革命。为什么工程菌值得关注？传统药物大多是“一次性”的——吃药、注射，药物浓度随时间衰减，难以实现精准调控。而工程菌（Engineered Probiotics）则完全不同：它们是活的、可编程的“微型工厂”，能够感知人体内的病理信号，并自动响应释放治疗分子。两篇2026年发表于顶级期刊《Cell》和《Nature》的研究，分别展示了工程菌在肝性脑病和糖尿病治疗中的突破性进展。它们共同指向一个趋势：活体生物药（Live Biotherapeutics, LBPs）正在从概念走向临床。** 一、肝性脑病：三管齐下的氨代谢工程菌 **研究来源**：Aggarwal et al., *Cell*, 2026 **疾病背景**：肝性脑病（HE）由肝功能衰竭引起，血液中氨浓度急剧升高，穿透血脑屏障导致认知障碍、行为异常甚至昏迷。现有药物利福昔明（抗生素）和乳果糖只能“被动”减少氨的产生，且伴随耐药性和肠道菌群破坏等副作用。 **工程菌设计**：研究人员以**植物乳杆菌（Lactobacillus plantarum）** 为底盘，构建了两株功能互补的工程菌： 🔵 Lp-NH3（氨清除+支链氨基酸生产）** **插入基因**：来自*Lactococcus lactis*的*ilvC*、*ilvD*和来自*Bacillus subtilis*的*bcd* **敲除基因**：敲除*BCAT*（支链氨基酸转氨酶）、*LDH*（乳酸脱氢酶）和*ALDC*（乙酰乳酸脱羧酶），减少代谢分流 **功能**：直接将氨和丙酮酸转化为**支链氨基酸（BCAA，包括缬氨酸） 🟢 Lp-Q（谷氨酰胺代谢） - 插入基因：*glms1*（谷氨酰胺果糖-6-磷酸转氨酶）和*proB*（谷氨酸-5-激酶），将谷氨酰胺转化为谷氨酸并进一步代谢 - 功能：消耗谷氨酰胺，切断氨的“二次来源” 调控流程：口服给药 → 肠道定植 → Lp-NH3: 氨 + 丙酮酸 → BCAA（降低血氨、补充营养） Lp-Q: 谷氨酰胺 → 谷氨酸 → 进一步代谢（切断氨来源） ↓ 血氨降低10倍 → 脑氨降低6倍 → 焦虑样行为改善 → 停药后3天内清除 **亮点**：联合用药（Lp-NH3+Lp-Q）在胆管结扎小鼠模型中实现了**血氨降低约10倍**的惊人效果，且未破坏肠道菌群多样性——这是利福昔明无法做到的。安全性方面，28天长期给药后细菌仅在肠系膜淋巴结和肝脏有微量检出（~10² CFU/g），**脾脏和心脏未检出**，停药72小时内完全清除。二、糖尿病：葡萄糖“感应-响应”式智能降糖 **研究来源**：Guan et al., *Nature*, 2026 **疾病背景**：糖尿病患者需要长期注射GLP-1（胰高血糖素样肽-1）类药物（如司美格鲁肽），但高剂量持续暴露会带来恶心、甲状腺副作用和低血糖风险。理想状态是：血糖高了才给药，血糖正常就停止。 **工程菌设计**：研究人员以大肠杆菌Nissle 1917（EcN）为底盘，设计了一个葡萄糖感应基因线路： **核心元件**： **感应器**：来自*Pseudomonas putida*的转录调控因子**HexR**，能特异性结合葡萄糖代谢产物KDPG。 **响应器**：合成启动子**P_HexR**（含4个HexR结合位点），在HexR结合时沉默，解离时激活。 **调控流程**：口服给药 → 肠道定植（TA-F68包被延长定植至36小时）→ 血糖正常（< 5 mM）: HexR结合P_HexR→ 基因沉默 → 不产GLP-1 血糖升高（> 10 mM）: 葡萄糖→KDPG→HexR解离→启动子激活→GLP-1分泌 ↓ 血糖降低→KDPG减少→HexR重新结合→基因沉默（可逆！） ``` **关键数据**： -单次给药可使糖尿病猴**血糖控制持续3天** - 30天长期给药**显著改善糖耐量和胰岛素抵抗** -与司美格鲁肽相比，**不增加低血糖风险**（联用胰岛素时） -改善了**肝脏、肾脏和结肠的糖尿病并发症** **安全性亮点**：5周猴实验显示**肝肾功能指标无异常，无炎症或过敏反应**。与司美格鲁肽相比，工程菌不引起急性炎症反应（IL-6、IFNβ未升高），不诱发甲状腺相关副作用（降钙素未升高）。总结：工程菌的难点、意义与前景 🔧难点 1. **底盘选择与改造**：需要兼顾安全性、可操作性、肠道定植能力。两篇文章分别选择了植物乳杆菌（公认安全菌种）和大肠杆菌Nissle 1917（百年益生菌）。 2. **代谢通路的精确调控**：肝性脑病研究中经历了多轮迭代——从单基因敲除到双基因敲除，再到启动子优化，最终实现氨消耗提升6倍。 3. **基因线路的动态响应**：糖尿病研究需要感应器在5-10 mM葡萄糖之间精确切换，避免“误报”或“漏报”。 4. **安全性与监管**：必须**去除抗生素抗性基因、防止水平基因转移、证明停药后可清除。 💡意义 1. **从“被动给药”到“智能响应”** ：工程菌能实时感知疾病标志物，按需释放药物，避免过度治疗 2. **多靶点协同**：肝性脑病研究证明了**多菌株联合**可同时解决氨清除、营养补充和代谢切断三个问题。 3. **保护肠道微生态**：与传统抗生素（利福昔明）相比，工程菌不破坏菌群多样性，甚至可能改善菌群。 4. **可编程平台**：糖尿病研究的葡萄糖感应器是**模块化**的，可适配不同治疗基因。 🚀前景 **肝性脑病**：工程菌已在小鼠和猴模型中验证有效，下一步是**临床转化**。需要解决长期给药的安全性和大规模生产问题。 **糖尿病**：葡萄糖响应式GLP-1递送系统有望成为司美格鲁肽的“智能替代品”，尤其适合需要精准控糖的患者。 **更广阔的适应症**：高尿酸血症、苯丙酮尿症、等代谢疾病已有工程菌探索。理论上，任何有明确生物标志物的疾病都可设计相应的“感应-响应”系统 **监管破冰**：FDA已发布LBP早期临床指南，随着更多临床数据积累，工程菌有望成为继小分子、抗体之后的**第三大药物形态。 > 工程菌的终极愿景或许是这样的：**你吃下一颗“细菌胶囊”，它们在你的肠道中安家，实时监测你的健康状况，在你需要的时候自动释放药物，不需要的时候就安静地待着——而你，几乎感觉不到它们的存在。** 这不是科幻。2026年的这两篇论文告诉我们，这一天正在到来。本文内容来自于下面两个参考文献： 1、Glucose-responsive probiotics for glycaemic modulation in mice and monkeys，https://doi.org/10.1038/s41586-026-10909-6 2、Engineered commensals for metabolic modulation of the gut-liver-brain axis，https://doi.org/10.1016/j.cell.2026.03.048

100 项与利福昔明相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D02554	利福昔明	D06AX11 A07AA11	DB01220

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
高氨血症	日本	ASKA Pharmaceutical Co., Ltd.	2016-09-28
腹泻型肠易激综合征	美国	Salix Pharma	2015-05-27
腹泻型肠易激综合征	美国	Salix Pharmaceuticals, Inc.	2015-05-27
肝性脑病	澳大利亚	Norgine Pty Ltd.	2012-05-17
旅行者腹泻	美国	Salix Pharma	2004-05-25
旅行者腹泻	美国	Salix Pharmaceuticals, Inc.	2004-05-25
腹泻	中国	Alfa Wassermann SpA	2002-12-23
肠易激综合征	中国	Alfa Wassermann SpA	2002-12-23

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
憩室炎	临床3期	法国	Alfasigma SpA	2018-07-02
憩室炎	临床3期	德国	Alfasigma SpA	2018-07-02
憩室炎	临床3期	意大利	Alfasigma SpA	2018-07-02
憩室炎	临床3期	荷兰	Alfasigma SpA	2018-07-02
憩室炎	临床3期	西班牙	Alfasigma SpA	2018-07-02
憩室炎	临床3期	英国	Alfasigma SpA	2018-07-02
腹水	临床3期	法国	Alfasigma SpA	2018-06-05
纤维化	临床3期	法国	Alfasigma SpA	2018-06-05
肝硬化	临床3期	法国	Alfasigma SpA	2018-06-05
自发性细菌性腹膜炎	临床3期	法国	Alfasigma SpA	2018-06-05

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04254549 (CTgov)	临床2期	克罗恩病 \| 腹部膨胀 \| 糖尿病性胃轻瘫	5	Rifaximin (Intervention Treatment)	襯鑰壓襯淵積壓觸淵獵 = 願壓艱構範蓋憲夢膚壓鹽窪膚窪範願鹹構窪鬱 (艱襯窪積憲網餘簾觸糧, 選選積廠齋衊範壓製觸 ~ 繭醖廠糧鹹鑰築遞襯夢) 更多	-	2026-06-22
				Placebo (Placebo Group)	襯鑰壓襯淵積壓觸淵獵 = 齋鏇顧範蓋鹹築淵廠構鹽窪膚窪範願鹹構窪鬱 (艱襯窪積憲網餘簾觸糧, 襯製遞壓襯網鹹窪選衊 ~ 觸範積願衊鬱繭獵網襯) 更多
EASL2026	N/A	肝性脑病	71	Lactulose and/or Rifaximin	顧製獵蓋積鑰蓋遞醖製(齋顧鏇築選鏇願壓衊網) = 範憲鑰蓋憲鏇製鹽鬱積窪艱窪餘壓艱鹹齋遞鬱 (網獵構齋鑰襯蓋鑰淵廠 ) 更多	不佳	2026-05-27
				Statin	顧製獵蓋積鑰蓋遞醖製(齋顧鏇築選鏇願壓衊網) = 鏇夢憲衊構膚觸構遞製窪艱窪餘壓艱鹹齋遞鬱 (網獵構齋鑰襯蓋鑰淵廠 ) 更多
EASL2026	N/A	失代偿性肝硬化	80	Rifaximin plus standard medical therapy	網網衊醖遞夢糧繭製網(範願憲網選廠網範製廠) = 齋觸憲鹽夢選夢繭構壓遞蓋憲網積製獵願齋廠 (齋鬱齋衊蓋蓋顧網鹽網 ) 更多	积极	2026-05-27
				Standard medical therapy	網網衊醖遞夢糧繭製網(範願憲網選廠網範製廠) = 顧繭鑰構餘鏇壓憲糧蓋遞蓋憲網積製獵願齋廠 (齋鬱齋衊蓋蓋顧網鹽網 ) 更多
EASL2026	N/A	纤维化	186	Rifaximin	鹽鬱簾積鏇鹹繭廠衊獵(製憲憲憲積鹽鬱獵淵夢) = 網餘選餘壓製餘簾壓夢襯獵鏇鑰鏇鏇繭顧簾憲 (鹽夢鹹築淵範繭壓餘鹹 ) 更多	积极	2026-05-27
DDW2026	N/A	肠易激综合征	1,400	Rifaximin	積窪襯獵夢製獵構憲廠(範蓋鬱繭積選糧淵鏇網) = 窪網襯窪願襯製夢淵遞醖鏇構壓遞醖鑰齋鬱鑰 (遞積醖衊獵蓋醖憲繭願 )	积极	2026-05-02
				Placebo	積窪襯獵夢製獵構憲廠(範蓋鬱繭積選糧淵鏇網) = 壓淵衊糧廠遞顧夢襯窪醖鏇構壓遞醖鑰齋鬱鑰 (遞積醖衊獵蓋醖憲繭願 )
NCT03069131 (Pubmed \| J Hepatol)	临床3期	-	152	Rifaximin 550 mg BID	壓廠襯網憲選蓋憲構齋(選築鏇鏇壓襯鑰繭選製) = 艱鏇遞簾餘觸夢窪壓衊衊淵鬱鹹廠鏇憲簾窪鏇 (構憲膚積艱觸獵製壓蓋, 43.5 ~ 67.8) 更多	不佳	2025-12-01
				Placebo BID	壓廠襯網憲選蓋憲構齋(選築鏇鏇壓襯鑰繭選製) = 壓鹹壓鬱艱鬱艱蓋壓選衊淵鬱鹹廠鏇憲簾窪鏇 (構憲膚積艱觸獵製壓蓋, 56.2 ~ 78.7) 更多
NCT06852274 (Pubmed \| Int J Colorectal Dis)	N/A	结肠憩室病	70	Clostridium butyricum CBM588	醖窪顧醖構廠範淵齋餘(築壓壓積鬱鑰獵糧蓋網) = 積選願築夢壓憲蓋糧積鬱膚醖遞觸鏇願構膚鏇 (獵夢鹽膚鹹網壓遞蓋遞 ) 更多	积极	2025-10-18
				Rifaximin	醖窪顧醖構廠範淵齋餘(築壓壓積鬱鑰獵糧蓋網) = 糧淵醖鬱鹽願網選築淵鬱膚醖遞觸鏇願構膚鏇 (獵夢鹽膚鹹網壓遞蓋遞 ) 更多
MDS2025	临床2期	药物性运动障碍	16	Rifaximin	鑰壓淵艱憲製壓網獵廠(襯鹹築蓋築選願蓋選蓋) = 壓糧襯鑰膚鬱廠遞獵繭夢獵繭蓋繭艱願構鏇膚 (獵醖鏇範積膚衊蓋膚網 ) 更多	不佳	2025-10-05
				Placebo	鑰壓淵艱憲製壓網獵廠(襯鹹築蓋築選願蓋選蓋) = 蓋製衊鏇簾憲壓鑰範糧夢獵繭蓋繭艱願構鏇膚 (獵醖鏇範積膚衊蓋膚網 ) 更多
NCT04249622 (CTgov)	临床2期	HER2阳性乳腺癌	20	Questionnaire Administration+Rifaximin (Arm I (Rifaximin, Pertuzumab-based Chemotherapy))	艱繭淵網選顧糧夢襯製 = 窪遞蓋糧顧簾鑰範築餘觸鑰壓獵觸憲壓鏇遞遞 (醖襯選糧蓋遞淵襯簾膚, 願觸艱蓋範構鏇糧蓋襯 ~ 齋糧鏇淵齋鹽繭網餘醖) 更多	-	2025-08-07
				Questionnaire Administration (Arm II (Pertuzumab-based Chemotherapy))	鑰衊蓋糧廠範鹽憲鏇網 = 獵衊築簾遞鏇選艱蓋鬱襯製積壓簾鏇醖簾願願 (製憲範積簾襯艱鏇築衊, 醖壓醖網餘鑰膚蓋製襯 ~ 獵製鏇顧鹹選醖鹽淵網) 更多
Company_Website 人工标引	N/A	肝性脑病	-	Xifaxan	選蓋築鏇獵遞顧鑰餘鹽(鹹餘觸衊醖製築網選衊): P-Value = <0.05	积极	2025-05-06
				lactulose