Biomes, They are A-Changin’

Why your microbiome is considered an ‘essential organ’

Photo Credit: NIH

The human body is a well-oiled machine. Millennia of evolution have selected for an efficient set of body systems that harmonize to allow us go about our daily activities without needing to consciously worry about breathing, maintaining a constant temperature, and providing energy to our hardworking cells. This is the idea of homeostasis: our body’s ability to maintain steady-state conditions. Homeostasis keeps us running in the face of external changes, from seeing the first light of day, to an excruciatingly spicy bite of a chili pepper, to a deep dive into an icy lake.

With an end result that amounts to a more or less flat line, homeostasis sounds passive — but it’s quite the opposite. For instance, a great deal goes into maintaining our circadian rhythm, or the body’s sleep-wake cycle. In most organisms, the internal clock is set to a 24-hour cycle, in keeping with light and dark. While cycling through each day, body temperature, stress hormones, wakefulness, and even digestion and metabolism are synced up to achieve balance within. But we don’t do it alone. More and more, we’re finding that our gut microbiome, the bustling community of microorganisms in our intestines, is intimately involved in this rhythmic ebb and flow.

In the past several decades, research on the gut microbiome has connected the bugs that live in our colon with just about every aspect of health and wellbeing imaginable, from digestion to immune function to social behavior. In many cases, the microbes that inhabit the body have so much impact on their host’s function that the microbiome is considered an essential organ in and of itself. Now, some of the newest research is revealing that these powerful microbes are affected by — and may even be in control of — some of the body’s important rhythms as well.

Way to Glow

The idea that the human gut microbiome undergoes cycling is a relatively recent one. However, scientists have known for years that these fluctuations occur in other species — including a small creature that spends its life underwater.

The bobtail squid has a unique set of worries. As a nocturnal sea-dweller, this aquatic creature is particularly susceptible to predators that simply look up — and see the shadowy squid silhouette backlit by the moonlight streaming into the waters above. But this little squid has a trick up its sleeve: a cloak of invisibility — not a Deathly Hallow, but an illusion by collusion between squid and bacteria. Each bobtail squid bears a light organ that houses bioluminescent bacteria called Vibrio fischeri, which, in the moonlit waters, produce a glow that helps the squid blend perfectly into its spotlight. The microbes eagerly populate the squid’s light organ for food and shelter, and the squid use their light to avoid becoming a midnight snack.

But the bobtail squid is hardly the perfect innkeeper. Bioluminescence is only really useful for the nocturnal squid at night, when it’s most active. As the sun rises, the squid will nestle into the soft sand at the bottom of the sea to sleep. Before slumber, the bobtail squid will actually expel about 90–95% of the bacteria living within its light organ. Scientists think this may be because the upkeep of the bacteria, which require nutrients and space, is no longer worth the trouble in the light of day, when the squid is safely hidden on the ocean floor. Expelling the bacteria essentially turns off an unneeded nightlight.

But the process doesn’t end there. The few bacteria left in the light organ spend the rest of the day building their numbers back up to nighttime levels. Along the way, these bacteria will be joined by others the squid takes in from the surrounding waters.

Acquiring and jettisoning an entire community of organisms on a daily basis is no small feat, and the bobtail squid’s metabolism changes dramatically over the course of the day to increase or decrease its hospitality towards V. fischeri. As night falls, the squid produces more food and oxygen for the growing numbers of bacteria entering and reproducing within the light organ. This process switches off during the daylight hours, and the cycle begins anew.

While you weren’t sleeping…

Like the bobtail squid, humans harbor some serious microbial firepower in their bodies. But unlike the bobtail squid, it is not in our best interests to perform a daily purge. Considering the enormous number of changes our body undergoes over the course of a single day — sleeping to waking, fasting to feasting, sweaty to squeaky clean — it’s only natural that our gut microbes must adjust to keep up.

One of the most important changes the human body undergoes on a daily basis is the transition from wake to sleep. Melatonin, the hormone our body produces nightly (and during the infamous post-lunch lull) to induce sleepiness, signals to the body that it’s time to rest and consequently slows down our metabolism. To match their human hosts, microbes sensing these hormonal changes also quiet down their processing of nutrients at night.

And while scientists don’t yet fully understand the full breadth of these cyclic changes, it’s clear that there are many ways in which the daytime microbiome differs from the nighttime microbiome. For instance, our microbiome’s ability to communicate with and bolster the immune system also appears to be dampened at bedtime, when nightly bursts of hormones signal the body to rest. Because of this, you may be at greater risk of disease if you’re exposed to an infectious pathogen at night. Similarly, our gut microbes affect the body’s ability to process drugs. For example, studies in mice suggest that microbes might be better equipped to forestall liver damage from high doses of acetaminophen during waking hours than at night.

Clearly, gut microbes are sensitive to changes in their local environment. But this relationship isn’t a one-sided dictation — it’s a conversation. The microbes in our gut can also seize the reins and exert their own effects on the body’s ability to maintain homeostasis — a fact that comes into particular focus when we examine cases in which the gut’s clock and the brain’s clock misalign.

For example, hitting gut microbes with calories late at night, when they are primed to expect sleep and not food, may have negative consequences for fat metabolism and weight gain. For anyone who has slogged through the groggy shifts in appetite that accompany jet lag, it may be unsurprising that inconsistent bedtimes and travel across time zones increases the risk of obesity, fat retention, and metabolic disorders such as type 2 diabetes. In fact, transferring the gut microbes of jet-lagged people into mice quickly made them pack on pounds.

At the extremes of irregular sleep-wake cycles, scientists have found that shift workers whose schedules go against the body’s natural inclination to sleep when it’s dark and be active when it’s light are more likely to suffer from metabolic disorders. To make matters worse, the stress brought on by lack of sleep and an inconsistent schedule can further disrupt the microbiome, potentiating the cycle of dysregulation.

Fortunately for those who travel and work inconsistent schedules, all is not lost. Regular, healthful meals at scheduled times can help put the gut microbiome back on track.

What’s in season?

Microbe cycling is a normal part of daily life — but these changes in our gut can operate on larger time scales as well. Recent work has shown that human gut microbiomes can actually shift dramatically over the course of the year on seasonal diets, such as those of hunter-gatherer Hadza communities.

Hadza seasonal eating goes far beyond using up the extra zucchini from your local farmer’s market. Their diets in different seasons have little overlap, relying on the seasonal availability of local plants and huntable game in Tanzania. Vegetation forms the bulk of the Hadza diet during the wet season, when berries and honey are plentiful. During the dry season, the Hadza spend more of their time hunting warthogs, antelope, and giraffes. Tubers and baobab fruits are year-round staples.

Different microbes prefer different foods — and accordingly, the gut microbiome is just as seasonal as the food. In fact, the gut can reconfigure so much over the course of a year that certain species will disappear during the wet season only to reappear for the next dry. Scientists are unsure if the returning microbes are being reintroduced through seasonal foods, or if their numbers slowly build back up from undetectable levels when fed by certain nutrients. Either way, what’s clear is this: even though the recalibrations that go on between seasons can be quite drastic, each Hadza year looks more or less the same. The gut microbiome is resilient, and seems to even thrive (and help the Hadza thrive) on this seasonal ebb and flow of nutrients.

Our gut microbiomes are deeply, irrevocably in tune with our bodies. They are clearly part of cycles small and large, daily and annual. But we have just scratched the surface of the myriad ways the gut microbiome can affect our wellbeing. From controlling our sleep-wake cycle to shifting with our metabolic needs, our gut bacteria are showing themselves to be just as dynamic as their human hosts.

I Contain Multitudes is a multi-part video series dedicated to exploring the wonderful, hidden world of the microbiome.

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