Immunity:酸奶并非百益无害!研究发现其或能助癌

2022-03-15 “国际科学”微信公众号 “国际科学”微信公众号

我们常喝的酸奶中含有大量的乳酸菌,虽然这些益生菌对我们的肠道健康很有帮助,但同时,这也是一种对我们的身体存在潜在威胁的细菌,并非百益而无一害,值得人们重视起来。

酸奶作为人们的日常饮品,已经有将近5000年的历史了。它含有丰富的乳酸菌、蛋白质、钙、碳水化合物以及多种微量元素。对于乳糖不耐受的群体来说,喝酸奶是一个非常不错的选择,且其中含有的大量益生菌能够帮助人们改善肠道菌群,从而能有效地调节便秘,促进减肥。

然而,就在不久前,这种在人们看来“人畜无害”的健康食品却被贴上“癌症帮凶”的标签。一项最新的研究表明,乳酸菌,一种被认为可以促进肠道健康的细菌,能通过影响色氨酸的代谢从而影响巨噬细胞的功能,促进肿瘤生长。

这项研究于今年2月份发表在Immunity期刊上,文章名为“Tryptophan-derived microbial metabolites activate the aryl hydrocarbon receptor in tumor-associated macrophages to suppress anti-tumor immunity”,中文译作“色氨酸衍生的微生物代谢物激活肿瘤相关巨噬细胞中的芳烃受体以抑制抗肿瘤免疫”。研究团队来自多伦多大学医学院。

图1 研究成果(图源:Immunity)

这项工作的重点是研究微生物组与癌症的负相关,并表明在某些情况下,微生物组的组成部分可能会对癌症治疗产生负面影响。研究人员检查了AHR(芳烃受体)对胰腺导管腺癌(PDAC)中相关巨噬细胞(TAM)功能的影响。AHR是色氨酸代谢产物的传感器和有效的免疫调节剂,是一种调节基因表达的蛋白质,它可以在身体的其他部位实现有益的炎症和免疫抑制。结果表明,TAM(巨噬细胞)中AHR的缺失或抑制会导致胰腺癌的生长减少、对治疗的敏感性提高以及炎性T细胞的数量增加。研究小组补充道,患者微生物群似乎会影响PDAC的结果。

在长期PDAC幸存者中,增加的微生物组多样性与TME(肿瘤相关巨噬细胞)的存活率和免疫学特征相关。已报道的小鼠模型粪便移植研究也表明,微生物群可以促进或抑制肿瘤进展并影响TME细胞的组成。在进行实验时,研究人员在PDAC的TAM中删除了AHR,或者在药理学上抑制了AHR活性。结果发现,AHR功能的丧失会导致肿瘤的体积减小,相反,AHR的激活则会阻碍这些有益的效果。具体来说,AHR能够控制胰腺癌中的肿瘤相关巨噬细胞的功能,而抑制AhR功能可以改善T细胞的功能,从而抑制肿瘤生长。

并且,泛癌分析表明,与大多数癌症类型相比,PDAC(胰腺导管腺癌)患者表现出了更高的AHR。在PDAC患者中,高AHR表达与疾病快速进展、死亡率以及免疫抑制TAM表型相关。此前已有研究表明,乳酸杆菌与AHR活性相关,且这两者都可以促进癌症的生长。

论文作者进一步指出,针对AHR的首次人体临床试验已经在晚期实体肺、结直肠和尿路上皮肿瘤患者中启动,以检测AHR抑制在多种癌症类型中的存在。最终,这些试验将为AHR是否是癌症治疗的合法目标提供明确的测试。研究人员McGaha表示:“我们的研究结果表明,针对微生物组的免疫反应可能对治疗产生有意义的影响,增强微生物组操作方法或可能通过精确抑制对微生物代谢物的反应来绕过对微生物组的操作。”“例如粪便微生物群移植,这些疗法一直受到肠道细菌的复杂性和多样性的阻碍。而这项研究通过精确定位对微生物代谢物的免疫反应,有可能绕过操纵微生物组的需要,这是我们想要探索的一个很酷的新方向。”

尽管胰腺癌相对罕见,但它是加拿大第三大致命癌症。在过去的三十年里,患有这种疾病的患者没有发现与其他癌症一样的生存改善。尽管癌症治疗已经取得了很大进展,但是,研究人员对于胰腺癌治疗方法的突破仍然非常重视。

总的来说,乳酸杆菌促进癌症生长的具体机制可以这样来阐述:乳酸菌将色氨酸代谢为吲哚,而吲哚是色氨酸代谢产生的一种代谢物,能够激活AHR。AHR又是巨噬细胞中的成分,作为人体的免疫细胞,巨噬细胞在肿瘤生长和转移中起着重要作用。所以,AHR表达越高,对肿瘤生长的抑制效果就越小。

我们常喝的酸奶中含有大量的乳酸菌,虽然这些益生菌对我们的肠道健康很有帮助,但同时,这也是一种对我们的身体存在潜在威胁的细菌,并非百益而无一害,值得人们重视起来。

原始出处:

Hezaveh K, Shinde RS, Kl?tgen A, et al. Tryptophan-derived microbial metabolites activate the aryl hydrocarbon receptor in tumor-associated macrophages to suppress anti-tumor immunity. Immunity. 2022 Feb 8;55(2):324-340.e8. doi: 10.1016/j.immuni.2022.01.006. PMID: 35139353; PMCID: PMC8888129.

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    2022-03-16 120d521dm50暂无昵称

    学习了

    0

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    2022-03-16 1dd9c9c9m27(暂无匿称)

    所以,不是越多越好,任何东西都该适可而止

    0

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    2022-03-16 weigq

    不吃酸奶了?😇

    0

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    2022-03-16 学医无涯

    学习一下

    0

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