In a healthy gut, microbes wax and wane throughout the day

In a healthy gut, microbes wax and wane throughout the day

Salk researchers find that metabolic disease and obesity may be caused, in part, by abnormal behavior of certain gut bacteria

LA JOLLA–Taking a single snapshot of all the bacteria that live in a mouse’s–or person’s–stomach and intestines can capture the health of the organism’s digestive system and even their risk of developing immune diseases and cancers. But it might take more than one snapshot to get a full picture, Salk researchers have discovered.

In a healthy, lean mouse, the gut microbiome–the full collection of microbes inside their digestive system–undergoes a complex daily cycle, according to new research. Some bacteria are found at highest levels during the night, for example, while others peak during the day. These fluctuations, however, disappear in obese mice, which could be a contributing factor to metabolic disease.

“Previously, the message was that there are beneficial microbes and there are harmful microbes,” says senior study author 萨奇达南达·潘达, an associate professor in Salk’s 调节生物学实验室. “We found that it’s more complex than this; different microbes are needed at different times of the day.”

In the new work, published December 2, 2014 in the journal 细胞代谢, Panda’s group compared the microbiomes of mice fed normal food versus those given high-fat chow. Rather than take one daily measurement of the animals’ gut microbes, they measured the populations of microbes every four hours. In the mice on normal diets–who eat during the night and sleep during the day–the researchers saw dramatic fluctuations in the particular genera of bacteria present at any given time. But in the mice that were on a high-fat diet–and generally eat around the clock, gain weight and develop diabetes–the microbes remained more constant.

The pattern was evident among multiple species of bacteria, including firmicutes, a type of bacteria other scientists have associated with obesity and disease.

“We showed that healthy mice can, in fact, have high firmicute levels during the night when they’re eating, but this wanes during the day when they’re fasting,” says Amir Zarrinpar, a 加州大学圣地亚哥分校 gastroenterologist who collaborated with Panda’s group. In obese mice, firmicute levels were, indeed, high all the time. The observation suggests that it’s not whether or not an organism has high firmicute levels that dictates health, but when or how often those levels peak–and the pattern wasn’t just seen among firmicutes.

When the researchers limited the food access of the obese mice so they could only eat during the night, some types of bacteria began fluctuating on a daily basis again–although not as many as seen in the mice on normal, lower-fat diets.

“The fact that we can restore some of these patterns with time-restricted eating shows that the timing of meals–not just what or how much is eaten–really matters to the microbiome,” says Zarrinpar. Fluctuations in the levels of bacteria, the researchers went on to show, can in turn cause fluctuations in bile acids–molecules that play key roles in controlling cholesterol levels, fat absorption and metabolism throughout the body. The researchers hypothesized that the flattening out of daily microbes cycles may be contribute to metabolic diseases by changing the daily fluctuations of these molecules.

The observation has immediate implications for basic research, Panda says. “Whenever anyone does any kind of microbiome research, they now need to pay close attention to what time of day all their experiments are done,” he says. But it also has an impact on human clinical studies of probiotics, bacterial mixtures which aim to encourage a healthy balance of microbes within the gut microbiome.

“Just like what times you eat throughout the day shapes your microbiome, what time you take a probiotic might change its effectiveness,” Panda explains. “If you’re taking a probiotic at a time when those particular microbes aren’t favored, it could alter those cycles of bacteria in a negative way. Likewise, if you take it at a time when those microbes are naturally rising, you could help encourage healthy cycling.”

Panda’s group has a plethora of questions remaining about how and why the bacteria fluctuate over a 24-hour cycle. They’d next like to investigate what factors change within the gut–from pH to immune molecules–in response to a high-fat diet that then alters what bacteria are present at different times.
Other researchers on the study were Amandine Chaix of the Salk Institute for Biological Studies and Shibu Yooseph of the J. Craig Venter Institute.

该项工作获得了以下机构的资助： 美国国立卫生研究院, ， 那个 Leona M. 和 Harry B. Helmsley 慈善信托基金, ，和 Glenn Foundation, as well as an American Gastroenterological Association Research Foundation Elsevier Pilot Research Award and an American Diabetes Association Mentor-Based Postdoctoral Fellowship.

关于索尔克生物研究所：
索尔克生物学研究所是世界顶尖的基础研究机构之一，其国际知名的教职员工在一个独特的、合作和富有创造力的环境中，探索生命科学的基本问题。索尔克科学家致力于科学发现和培养下一代研究人员，通过对神经科学、遗传学、细胞和植物生物学以及相关学科的研究，在癌症、衰老、阿尔茨海默病、糖尿病和传染病等领域取得了开创性的贡献，加深了我们对这些疾病的理解。.

教职员工的成就获得了无数荣誉，包括诺贝尔奖和美国国家科学院院士资格。该研究所由脊髓灰质炎疫苗先驱 Jonas Salk 医生于 1960 年创立，是一家独立的非营利组织和建筑地标。.