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Bacteria commonly found in the body contribute to stomach cancer, finds study
A new study has discovered that a type of bacteria commonly found in the body, which usually does not pose problems for healthy people, plays a significant role in causing stomach cancer, the fifth most common cancer in the world. The findings are published in the journal Cell.
Streptococcus anginosus bacteria exist alongside other germs in the mouth, throat, intestines and vagina. Occasionally, they may cause mild infections like sore throats and skin infections. For patients with underlying health conditions or compromised immune systems, the bacteria can lead to more serious infections, such as those that damage the heart and brain.
However, research co-led by Nanyang Technological University, Singapore (NTU Singapore) and the Chinese University of Hong Kong (CUHK) showed that S. anginosus is involved in stomach infections in mice that cause cell damage and changes known to encourage gastric cancer. This includes gastric inflammation, in which the stomach lining is irritated. The condition damages gastric lining cells and causes some of them to gradually transform into cancer cells.
Mice experiments also revealed that the bacteria spurred the growth of stomach cancer cells, doubling the size and weight of tumors in some cases.
But the researchers also found that disrupting a protein on the bacteria's surface, which they need to interact with stomach lining cells, reduced S. anginosus' ability to contribute to stomach cancer.
The findings add to the number of bacteria species known to cause gastric cancer. Another bacteria species, Helicobacter pylori, is known to cause gastric ulcers in people. These painful sores increase patients' risk of developing gastric cancer. Whether other bacteria are involved has remained unclear until now.
"Our latest findings in mice shed light on another pathogen that contributes to stomach cancer, and how it does so," said the study's co-lead, Professor Joseph Sung, NTU's Senior Vice President (Health and Life Sciences).
"This lays important groundwork for further studies in humans that will help clinicians better treat and prevent gastric cancer driven by bacteria," added Prof Sung, who is also the Dean of NTU's Lee Kong Chian School of Medicine.
Professor Yu Jun, the study's other co-lead who is Director of CUHK's State Key Laboratory of Digestive Disease, said that the researchers will next "explore the therapeutic potential of targeting S. anginosus to reduce gastric inflammation and cancer risk."
The S. anginosus study contributes to one of the goals of the NTU 2025 strategic plan to address the needs and challenges of healthy living.
Bacteria-induced abnormalities
H. pylori bacteria are classified as carcinogenic (cancer-causing) to humans. But among people infected with the bacteria, only 1 to 3% develop stomach cancer, which suggests that other factors are involved in its development.
Past research has shown that 20% of patients with chronic gastritis—a known contributor to gastric cancer—are not infected by H. pylori. Chronic gastritis refers to long-term inflammation of the stomach.
Studies have also posited that other bacteria, including S. anginosus, could play a part in stomach tumor development too.
To confirm S. anginosus' role, Prof Sung and collaborating scientists from CUHK ran a series of experiments.
The researchers infected the stomachs of mice with S. anginosus over two weeks and found mild to moderate gastric inflammation. This was similar to what was observed in mice infected with H. pylori over the same time frame.
When Streptococcus anginosus infection occurred at stomach tumors implanted under mice skin, the bacteria spurred the growth of the gastric cancer cells, doubling the size and weight of tumors in some cases (middle row), compared to tumors without Streptococcus anginosus infection (top row). When a specific surface protein of the bacteria was genetically removed, the bacteria's ability to encourage tumor growth was impaired (bottom row).
When S. anginosus infection of the mice was extended—by up to a year—persistent and prolonged inflammation of the stomach, or chronic inflammation, was observed three months after the initial infection. The level of inflammation was also similar to that of rodents infected by H. pylori only.
But when mice were co-infected by both S. anginosus and H. pylori, the level of chronic gastric inflammation recorded after three months was two times greater than infection by either bacteria alone.
As the S. anginosus infection progressed, anomalies that signal cancer development were also observed in the stomach. There was a surge in gastric cell numbers six months after the original infection, stomach acidity rose after nine months, and many cells of the stomach lining transformed into abnormal pre-cancerous cells after 12 months.
The scientists observed another way that S. anginosus infection created an environment conducive to gastric cancer—by disrupting the population of other microorganisms in the stomach. The bacteria increased the number of stomach microbes that typically reside in the mouth while reducing the number of probiotic bacteria important for good gut health, like Lactobacillus.
They demonstrated that S. anginosus was able to drive the growth of gastric tumors. When stomach cancer cells were implanted under the skin of mice or into the rodents' stomach lining, infection by S. anginosus at those sites encouraged the tumors to grow, doubling their size and weight in some cases.
The researchers also discovered that the bacteria needed a specific protein on their surface to physically bind to and invade stomach lining cells to promote gastric cancer development. When this protein was deficient in the bacteria, the germs' ability to bind to stomach lining cells and encourage the growth of gastric cancer implants was impaired.
Prof Sung said, "Our results suggest that long-term S. anginosus infection causes intensive chronic gastritis that is comparable to H. pylori infection. In fact, these two pathogens might act collaboratively to promote gastric inflammation and, eventually, gastric cancer. This could change how we approach prevention and treatment of the disease."
He added that detecting S. anginosus in feces could be useful for assessing whether a patient is at risk of gastric cancer in the future.
Since S. anginosus is commonly found in the mouth, the bacterium could be swallowed through saliva and find its way into the stomach. So, one potential way to guard against stomach cancer from developing could be to practice good oral hygiene, said Prof Sung.
注释：
Streptococcus anginosus: n
表示"咽峡炎链球菌"， 其中streptococcus意为“ 链球菌”，如：group A streptococcus 甲类链球菌；anginosus 意为“ 咽峡炎病, 咽痛病“。
gastric: adj
表示" 胃的"，means "relating to or involving the stomach"，如：Gastric juices help us digest our food. 胃液能帮助消化。
Helicobacter pylori
表示" 幽门螺旋杆菌"，如：Gastritis is often accompanied by infection with Helicobacter pylori. 胃炎常伴有幽门螺旋杆菌的感染。
carcinogenic: adj
表示"致癌的"，means "causing or tending to cause cancer;"，如：Didn't you know smoking is carcinogenic? 你不知道抽烟会致癌吗?
posit: v
表示" 假定"，means "take as a given; assume as a postulate or axiom"，如：Most religions posit the existence of life after death. 大多数宗教都假定人死后生命仍存在。
Lactobacillus: adj
表示" 乳酸杆菌"，means "a Gram-positive rod-shaped bacterium that produces lactic acid (especially in milk)"，如：It is traditionally made by adding common strains of Streptococcus and Lactobacillus bacteria to raw milk. 传统制作是在鲜奶里添加嗜热链球菌或保加利亚乳酸杆菌。
中文简要说明：
以往的医学消息认为，癌症是细胞突化癌变引起的，并不是病原体引发的。但是愈来愈多研究发现，有一些癌症确实与细菌有关。一种口腔内常见的链球菌通常不会对健康人体造成问题，但是如果杂掺各种因素，它就可能导致胃癌，所以请注意口腔卫生。
医疗讯息(MedicalxPress)报导，咽峡炎链球菌(Streptococcus anginosus)颇为常见，它与其他细菌一起经常存在于口腔、喉咙、肠道和阴道。有时，它们过度增生可能会引起轻微感染，例如喉咙痛和皮肤感染。这对健康人来说不算大问题，但是在临床上还是要小心，因为免疫系统受损的患者，这种细菌可能导致更严重的感染。
另一方面，新加坡南洋理工大学（NTU Singapore）和香港中文大学（CUHK）共同领导的研究表明，咽峡炎链球菌与小鼠胃部感染有关，它会导致细胞持续损伤造成胃部发炎，这种情况会损害胃壁细胞，就有可能导致其中一些细胞逐渐转变为癌细胞。小鼠实验还表明，这种细菌还会推快胃癌细胞的生长，在某些情况下，肿瘤的大小和重量会增加到一倍。
但研究人员也发现，它并不算难以治疗，只要破坏细菌表面的一种蛋白质（细菌与胃壁细胞相互作用所需的蛋白质），就会降低癌化的机率。
这个发现增加了我们对于引发胃癌的细菌种类数量。胃癌与细胞有关的研究，归功于两名澳洲科学家：华伦(Robin Warren)和马歇尔(Barry James Marshall)，他们在1982年发现胃部深夜的幽门螺旋杆菌，并大胆判定它是引发胃溃疡的元凶。这在当年不被科学界所相信，因为普遍的医学书籍都认为，细胞无法生存在胃酸当中。为了求证，马歇尔以自己为实验，服下含有幽门螺旋杆菌试管，果然让自己罹患胃溃疡，这才使科学界正视他们的研究。为了表彰这两位科学家的发现，华伦与马歇尔共同获得2005年诺贝尔生医奖。
回到原题目，南洋理工大学健康与生命科学的沈祖尧教授(Joseph Sung)说：「我们在小鼠身上的最新发现，揭示了另一种导致胃癌的病原体及其作用机制。这为进一步的人类研究，奠定了重要基础，有助于临床医生更好地治疗和预防，由细菌引起的胃癌。」
香港中文大学消化疾病国家重点实验室主任于军教授表示，研究人员下一步将要想方法治疗咽峡炎链球菌，以减少胃发炎和癌症风险。
幽门螺旋杆菌确定与溃疡有关，但胃溃疡不一定就会罹患胃癌。据统计，只有 1% 至 3%的胃癌患者确定有幽门螺旋杆菌，这表明一定还有其他病原体。
研究团队为了证实咽峡炎链球菌的作用，沈教授与中文大学的科学家们，进行了一系列实验；研究人员在两星期内用咽峡炎链球菌感染小鼠的胃，发现轻度至中度的胃发炎。这与在同一时间范围内，感染幽门螺旋杆菌的小鼠中观察到的情况相似。
但是，当小鼠同时感染咽峡炎链球菌和幽门螺旋杆菌时，它们的慢性胃发炎情况会变的更明显。而且感染后六个月，胃细胞数量激增，九个月后胃酸的酸度上升，12个月后，胃壁的许多细胞转化为异常的癌前细胞。
科学家观察到，咽峡炎链球菌感染后具有「排它性」，也就是会破坏胃中其他益生菌(例如乳酸菌)的数量。这使得胃变得更脆弱。
沈教授说：「我们的研究结果表明，长期的咽峡炎链球菌感染会导致与幽门螺旋杆菌感染相当的严重慢性胃炎。然后，两种细菌要是同时感染，那么它们协同作用将会更容易引发胃部发炎，最终导致胃癌。」
他补充说，检测粪便中的咽峡炎链球菌数量，可能有助于评估健检者是否有胃癌的风险。
由于咽峡炎链球菌常见于口腔中，这使得平时的吞咽都可能使这种细菌进入胃中。因此，沈教授说，预防胃癌发生的潜在方法，可能是保持良好的口腔卫生。
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