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科普:南京大学发现气单胞菌新亚型是溃疡性结肠炎的致病菌

  • 2026-06-16 03:54:11
科普:南京大学发现气单胞菌新亚型是溃疡性结肠炎的致病菌

南京大学朱敏生团队2025年11月在《Science》发表重磅研究:溃疡性结肠炎(UC)由一种新发现的细菌感染导致,致病菌是气单胞菌新亚种(Aeromonas sp. MTB),简称MTB菌 。

发病机制:MTB分泌气溶素,专门杀死结肠黏膜下的巨噬细胞(肠道“免疫哨兵”);哨兵一失,肠道对炎症极度易感,进而发展为溃疡性结肠炎 。

关键证据链:

1. UC患者肠道巨噬细胞提前消失(早于溃疡);

2. 近半数UC患者粪便含气溶素,可杀死巨噬细胞;

3. 分离出MTB菌,动物实验可复制出UC样病变 ;

4. 健康人很少检出MTB菌。

和“痢疾杆菌”的区别

痢疾杆菌(志贺菌):急性感染,不产生硫化氢,气味偏酸腐;不是UC病因 。

南大发现的MTB(气单胞菌):新确认的UC原发性致病菌;可长期潜伏定植,慢性低水平损伤免疫屏障,最终诱发UC 。

现状与意义

传统认知:UC是自身免疫+菌群紊乱的多因素病,无单一明确致病菌。

南大突破:首次把UC从“不明原因自身免疫病”改写为“可溯源的细菌感染驱动病” 。

临床前景:有望开发抗MTB菌药物或噬菌体疗法,实现根治(现有药只能控制) 。

南京大学2025年新发现的“气单胞菌MTB”才是慢性溃疡性结肠炎的关键致病菌。临床观察分隐匿携带期、轻症肠道不适、典型溃疡性结肠炎活动期。

一、核心特点

该菌株以结肠慢性定植、低持续损伤为主,和普通气单胞菌引发的急性肠胃炎不同:多数人初期无症状,缓慢进展,反复发作;核心损伤来自菌体定植+气溶素毒素破坏肠巨噬细胞、损伤黏膜屏障

二、分阶段症状

1. 无症状携带期(潜伏阶段)

健康带菌者、感染早期多见

表现:无明显腹痛、腹泻,饮食、排便基本正常

隐患:肠道免疫已悄悄受损,劳累、受凉、饮食刺激、滥用抗生素后极易发作

2. 前驱轻症(早期发作,易误诊为肠易激综合征)

这是最常见的初始表现,持续数月至数年:

1. 排便异常

大便不成形、溏软,每日排便2–4次;偶有糊状便,一般无明显脓血。

排便前后下腹隐痛、坠胀,排便后痛感可短暂缓解。排便不尽感、里急后重(总想排便,但排不出多少)。

2. 肠道产气与气味

腹胀、肠鸣增多;大便可伴酸腐味,一般无剧烈臭鸡蛋味

3. 全身轻微不适

间断乏力、食欲不振;部分人晨起腹部发凉、隐痛。

无高热、无明显呕吐(区别于急性食物中毒型气单胞菌感染)

3. 典型活动期(进展为类似慢性溃疡性结肠炎表现)

MTB持续产毒、肠黏膜反复糜烂溃疡,症状典型且反复:

腹泻加重。每日腹泻4次以上,重症可达十余次。粪便带黏液、血丝、鲜血,严重时典型黏液脓血便。

腹痛,左下腹、全腹持续性隐痛、绞痛,活动、进食生冷、辛辣后加重,里急后重显著,肛门坠胀、灼热感

肠道局部伴随表现肠黏膜糜烂渗出,部分患者出现肛周不适、肛周湿疹

4. 全身炎症表现

低热(37.3–38℃)多见,少有突发高热

长期反复腹泻导致消瘦、体重下降、营养不良。

乏力、失眠、情绪焦虑(肠道-脑轴受影响)。部分患者伴关节隐痛、皮肤轻微皮疹(肠外轻微炎症反应)。

4. 急性加重(诱因刺激后突发恶化)

常见诱因:暴饮暴食、生冷不洁饮食、饮酒、滥用抗生素、熬夜劳累、感染感冒。腹泻暴增,脓血便明显增多。阵发性剧烈腹痛、明显肛门灼热 严重者因频繁腹泻出现轻度脱水、电解质紊乱。

三、与普通气单胞菌急性感染的关键区分

1. 普通气单胞菌(嗜水气单胞菌等)

急性起病,突发高热、水样泻、剧烈腹痛、呕吐,类似急性食物中毒。病程短,抗感染后恢复快,一般不转为慢性。

2. MTB新亚种

隐匿起病、慢性迁延,以反复黏液便、脓血便、下腹坠胀为主。

低热或不发热,几乎无剧烈呕吐,极易慢性反复发作,最终进展为典型UC。

四、合并、继发表现

1. 菌群紊乱:腹泻与便秘交替出现

2. 肠屏障持续受损:反复出现口腔异味、嗳气、消化不良。

3. 长期慢性炎症:贫血、低蛋白、免疫力下降,更容易叠加大肠杆菌、志贺菌等其他肠道细菌混合感染

五、简易识别要点

满足多条需警惕MTB感染倾向:

1. 长期反复溏便、黏液便,时好时坏

2. 左下腹隐痛、排便不尽、肛门灼热;

3. 无明显饮食中毒史,却常年肠道不适

4. 肠镜提示结肠黏膜慢性炎症、糜烂、浅溃疡,常规抗炎治疗易复发。

MTB(巨噬细胞毒性气单胞菌)目前还没有上市的特效药;现有手段以“中和毒素+清除细菌+修复肠屏障+传统抗炎”为主,抗气溶素抗体是最有前景的根治方向(动物实验已成功,临床在推进)。

一、最根本:靶向中和气溶素(MTB的核心毒素)

抗气溶素(Aerolysin)中和抗体(南大团队,Science 2025)

机制:直接结合并中和MTB分泌的气溶素,不让它杀死肠道巨噬细胞。

现状:动物模型治愈级效果,临床正在开发/待上市。

优势:只打毒素,不抑制全身免疫,有望根治而非仅控制。

噬菌体疗法(在研)

针对MTB特异性噬菌体,精准裂解MTB,不伤正常菌群。

现状:实验室有效,临床未普及。

三、修复肠道屏障+抑制炎症(现在临床常用)

基础抗炎(传统UC方案)

美沙拉嗪(5-ASA):控制黏膜炎症、减少复发;

保护肠屏障+菌群调节

益生菌:双歧杆菌、乳酸菌,抑制MTB定植、恢复菌群平衡;

饮食:低刺激、少酒精、少加工食品;高纤维+发酵食物(无糖酸奶);

根治希望:抗气溶素抗体(中和毒素,动物已治愈,临床在路上);

现在能用:药敏指导下短程抗生素+美沙拉嗪+益生菌+抗炎饮食;

核心禁忌:别乱输广谱抗生素——越用MTB越容易定植。

在中医的世界里对腹泻、慢性腹泻腹痛结肠炎等有哪些方剂呢?在《伤寒杂病论》里涉及到腹泻、腹痛下利的方剂有:葛根汤,葛根加半夏汤,小建中汤,小柴胡汤,葛根芩连汤,白头翁汤,半夏泻心汤,生姜泻心汤,甘草泻心汤,赤石脂禹余粮汤,理中汤,桂枝人参汤,四逆汤,白通汤,黄土汤,白头翁加甘草阿胶汤,大柴胡汤,大承气汤,黄芩汤。其它书籍里还有痛泻要方、七味白术散、藿香正气散、芍药汤、补中益气汤、参苓白术散等。但是实际应用的时候辨证复杂,很难选对方剂,甚至把方剂挨个试一遍也常常没有什么效果。慢性腹泻慢性溃疡性结肠炎即使对中医来说想治愈也比登天还难。

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  1. CONNECT:[ UseTime:0.000706s ] mysql:host=127.0.0.1;port=3306;dbname=b460;charset=utf8mb4
  2. SHOW FULL COLUMNS FROM `fenlei` [ RunTime:0.000912s ]
  3. SELECT * FROM `fenlei` WHERE `fid` = 0 [ RunTime:0.007255s ]
  4. SELECT * FROM `fenlei` WHERE `fid` = 63 [ RunTime:0.002665s ]
  5. SHOW FULL COLUMNS FROM `set` [ RunTime:0.000889s ]
  6. SELECT * FROM `set` [ RunTime:0.001316s ]
  7. SHOW FULL COLUMNS FROM `article` [ RunTime:0.000745s ]
  8. SELECT * FROM `article` WHERE `id` = 583122 LIMIT 1 [ RunTime:0.009679s ]
  9. UPDATE `article` SET `lasttime` = 1783122923 WHERE `id` = 583122 [ RunTime:0.001386s ]
  10. SELECT * FROM `fenlei` WHERE `id` = 65 LIMIT 1 [ RunTime:0.000300s ]
  11. SELECT * FROM `article` WHERE `id` < 583122 ORDER BY `id` DESC LIMIT 1 [ RunTime:0.000611s ]
  12. SELECT * FROM `article` WHERE `id` > 583122 ORDER BY `id` ASC LIMIT 1 [ RunTime:0.000921s ]
  13. SELECT * FROM `article` WHERE `id` < 583122 ORDER BY `id` DESC LIMIT 10 [ RunTime:0.001150s ]
  14. SELECT * FROM `article` WHERE `id` < 583122 ORDER BY `id` DESC LIMIT 10,10 [ RunTime:0.004134s ]
  15. SELECT * FROM `article` WHERE `id` < 583122 ORDER BY `id` DESC LIMIT 20,10 [ RunTime:0.016820s ]
0.140883s