Microbiome – fad or future?

By Simon Cork, Neurophysiologist, Imperial College London, @SimonCorkPhD

You may have heard many scientists and media types getting excited over the term “microbiome” recently. There was a series on BBC Radio 4 termed “The Second Genome” recently dedicated to it, and a succession of articles on the BBC News website ^{1 2}. But what exactly is it, what does it do, and should we all be excited?

The microbiome is the term scientists give the community of bacteria that live in your guts (micro meaning small, and biome meaning biological community). People have been studying the microbiome for many years, and there is a remarkable amount of literature around the microbiome of insects. But recently, the microbiome of humans, and specifically the effects our microbiomes have on our overall health, has entered the spotlight.

In insects and other animals, the bacteria that live in and around them have remarkable effects not only on their heath but on their development. For many insects and animals, interactions with bacteria are a requirement for their survival. One particularly powerful example of the influence of bacteria on a host’s behaviour is in the fruit fly.

Feeding fruit flies different diets (and thus altering their gut microbiome composition) causes them to preferentially mate with flies fed on the same diet. When given antibiotics, which wipe out their bacteria, this preference disappears.

In humans, we are only just beginning to understand (or perhaps recognise) the importance that the microbiome has on our health. We are also beginning to understand how changes in our microbiome predispose, or even cause, certain diseases.

Less bacteria, more weight?

Take obesity for example. Worldwide, over 2.1 billion people are overweight or obese. The causes of obesity vary from person to person, but one common factor found in obese individuals is the lack of diversity of their gut bacteria. In a lean individual, the gut bacteria will contain a variety of different strains and species of bacteria. However, in individuals with obesity, this diversity is significantly reduced (with an increase in the ratio of the Firmicutes and a decrease in the Bacteoridates species).

We also know that babies who are born via caesarean section are at a higher risk of developing a number of health conditions in later life, one of which is obesity. The reasons why are not completely understood, but we know that C-section babies do not get the full complement of bacteria that babies born naturally get.

Essentially, in the first few months of life, a baby born via C-section has a gut bacterial population that more closely resembles that found on the skin, as this is often the first bacteria that they come into contact with.

Quite astonishingly, it may be possible that gut bacterial populations that predispose to disease act as a form of non-genetic inheritance of disease. For example, an obese mother, who likely has a bacterial population with a low diversity, may pass this low diversity to her child during delivery, thus predisposing them to obesity in later life.

So what does this mean? Well, the honest answer is we don’t quite know. At the moment, these observations are simply that, observations. We can predict whether or not a person will be obese or lean with 90% accuracy simply by studying the diversity of their microbiome, but what we don’t fully understand is how the bacteria are contributing to weight gain.

What’s in it for them: bacteria causing obesity? And other diseases?

One theory is that certain bacteria have the ability to harvest energy from our diets more effectively than others. Couple this with a sedentary lifestyle and you have the recipe for weight gain.

Another theory is that the bacteria are interfering with our brain chemistry. We know that many species of bacteria can secrete molecules that are either the same or have very similar chemistry to many of the molecules found in our brain, and we know that bacteria are able to secrete these chemicals in response to certain foods.

Could it be then, that our bacteria are driving our food choices? Imagine a population of gut bacteria that have a penchant for sugar; they use this as their main source of energy and want to make sure that it keeps coming. Is it possible that in response to their host eating a sugary meal, the bacteria release chemicals that tells their brain to eat more? This may sound far-fetched, but there’s increasing evidence that this may actually be happening.

There’s also increasing evidence that our gut bacteria may be driving a number of other conditions, including asthma, depression and anxiety, possibly through chemicals they release which interfere with our normal brain chemistry.

To each their own: individual differences and possible ways to shift them

So what can we do about this? Well, the bad news is this area of research is still very much in its infancy.

There are a few things we do know.

Our gut bacterial populations vary considerably from person to person, which makes a one-size fits all approach to fixing a dysfunctional microbiome tricky (although the microbiomes of people living in the same house are more similar than they are to the rest of the population).

The difficulty now is figuring out how we can shift this composition in later life. Unfortunately, downing a yoghurty probiotic drink containing a single strain of bacteria doesn’t really have much of an effect on the overall composition of the community in our guts. Many of the bacteria found in these drinks are not normally found in the guts of anyone – in fact they’re chosen largely because they can survive both the hostile journey from mouth to gut, and through the factory.

Our diets play a large role in the composition of our microbiome. And our microbiome populations become fixed during our early life. Differences in how we were delivered, whether we are breast fed or bottle fed, which country we grow up in and whether we share our house with pets, all affect the composition of our microbiome.

Perhaps the easiest way of shifting our microbiome is related to how much fibre we eat. Our bodies can’t digest dietary fibre on its own, and most of the fibre we eat makes its way to the end of our digestive tracts. This is where it feeds the bacteria in our guts, who in response not only increase their diversity (fibre feeds a lot of different kinds of bacterial species, who can all grow in its presence), but also release chemicals which are beneficial to our bodies’ health.

Poop pills: what do we know about this surprising possible obesity treatment?

However, there is another way we can shift our microbial population – faecal transplants. If we take an obese mouse, and feed its droppings to a lean mouse (thus transplanting its bacteria), that lean mouse will become obese – regardless of what it eats. The same is true if you take the gut bacteria from an obese human and transplant it into the gut of a lean mouse. That in itself is amazing.

But is the same true for humans? Well, faecal transplant (or FT) has been used clinically to treat C. difficile (or C-diff as it’s commonly known) infection. This nasty hospital-acquired infection is difficult to treat with standard antibiotics and, left unchecked, can be fatal. However, FT is an effective treatment for C-diff and is a cure for many people.

On the other hand, the literature surrounding its effectiveness for treating obesity in humans is controversial, and also risky. A lack of proper clinical trials means we don’t fully know whether it works or to what extent. Furthermore, FT has the potential to transmit a number of diseases, and given the increasing number of conditions that are being attributed to gut bacteria, the risk might just be too great given our level of understanding.

The bottom line: the future looks promising

So what’s the take home message? The microbiome is an exciting area of research, and undoubtedly will lead to treatments for a number of diseases in the future.

As it stands, our understanding is largely based on observational data – a case of correlation, rather than causation. But many people are confident causation is there, we just need the definitive proof.

In the meantime, the best thing we can do to feed our hungry bugs is to increase the amount of fibre in our diets and reduce unnecessary antibiotic use. The good news is that a lot of people are getting excited, and the gut microbiome is no longer the playground of just the microbiologists. Gut scientists, lung scientists and neuroscientists are all getting in on the action, and these collaborations are rapidly increasingly our knowledge of how the bacteria in our bowels are affecting our health. The time for the microbiome to really show its potential grows ever closer.

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¹ https://www.bbc.co.uk/programmes/b09zgykv

² http://www.bbc.co.uk/news/health-43674270

 

Early to bed and early to rise… makes a teen healthy, wealthy and wise? (Part 2)

By Gaby Illingworth, Rachel Sharman & Russell Foster; @OxTeensleep, @gabyillingwort1, @DrRachelSharman, @OxSCNi

To the possible dismay of parents hoping to start the family day bright and early, teenagers hit the hay and wake up at increasingly later times during adolescence – a delay of between one and three hours compared to pre-pubertal children.

Teenagers struggle to fall asleep early but still need to wake up for lessons during the school week, which contributes to a reduction in time spent asleep. At the weekend, the morning hours may well be spent snoozing to “catch-up” on lost Zzz’s.

In 2015, the National Sleep Foundation recommended that teenagers, aged 14 to 17 years, should be getting eight to ten hours of sleep a night. However, across the globe, teenagers are routinely not getting enough sleep, with older adolescents more likely to have insufficient weekday sleep than early adolescents. One of the consequences of insufficient sleep is that sleepiness during the day is common in this age group.

Sleep researchers have suggested some mechanisms behind this change in teenagers’ sleep timing.

How teenagers become owls: slower clocks, increased light sensitivity, or decreased sleep pressure

Although we don’t know why adolescent sleep changes, we do know that changes occur in the two processes which govern sleep – the circadian rhythm and sleep/wake homeostat. (Catch up on these two concepts in our previous post.)

The teenage biological clock has been proposed to run more slowly at this age, driving their sleep timing later, meaning their chronotype becomes more owl-like.

From DIVA007 on Flickr

Another suggestion is that their biological clock might be more sensitive to light in the evening (delaying sleep) and less sensitive in the morning (making them wake up later).

Adolescent sleep pressure is also thought to accumulate more slowly during the day, making them less tired when they reach the evening.

Jetlag without leaving the country

We know what jetlag feels like when we travel across time zones. Our internal time takes a while to adjust to the new external time.

Teenagers experience something similar with ‘social jetlag’: when their internal time (chronotype) is misaligned with social time (school commitments). At the weekend, they are more likely to be able to sleep according to their chronotype than during the school week. This misalignment of sleep/wake timing has been shown to associate with poorer cognitive functioning.

To blame the bright screens or not?

Teenagers’ lack of sleep is not all down to physiology. They, just like adults, may be engaging in behaviour that isn’t conducive to sleeping well.

The effect of light exposure on sleep has received increasing attention with the proliferation of electronic device use in recent years. However, the results are mixed.

One study on young adults asked individuals to read an e-book at maximum intensity under dim room light for around 4 hours (18:00–22:00) before bedtime on five consecutive evenings, whilst the control group read a printed book.

While the study concluded that those that read the e-book took longer to fall asleep, had lower morning alertness, and a delay of the circadian clock compared to reading a printed book, the effects were relatively small. Those participants who read e-books took only 10 minutes longer to fall asleep (Chang et al., 2015).

As a result, some caution needs to be exercised when the press reports that reading an e-book before bed has unintended biological consequences that may negatively affect performance, health, and safety.

Nevertheless, the impact of using electronic devices prior to sleep does seem to be important. In a large US survey, adolescents were shown to have increased the time spent using electronic media devices from 2009 to 2015.

This was correlated with a decline in sleep duration (Twenge et al., 2017), and light from such devices has been blamed. Such studies have encouraged the use of in-built or downloadable applications that can dim the brightness of screens and/or reduce the light emitted.

Light interventions are now being considered as a tool for adolescents experiencing difficulties with sleep, including reducing their exposure to evening light and increasing morning light to advance the clock to a time more suited for school.

Unfortunately, the evidence showing that such interventions can be helpful is lacking. Furthermore, it is important to stress that game use, social media, and watching TV are all likely to be cognitively arousing so teens may simply feel like staying up when they use electronic media devices.

As a result, disentangling the light effects versus the alerting effects of devices is complex and awaits good experimental studies.

Highly caffeinated

 

From Austin Kirk on Flickr

Caffeine is a stimulant with a half-life of approximately six hours in healthy adults (meaning that half of it is broken down in our bodies in six hours). It works by preventing the molecule adenosine, which promotes sleep, from having its effect in the brain, thus promoting wakefulness.

Teenagers are advised to consume no more than 100mg of caffeine per day, yet highly-caffeinated energy drinks are popular among teens. Many energy drinks contain higher caffeine levels than 100mg in a single can. Consuming caffeine later in the evening, or consuming it excessively throughout the day may be another contributory factor to delayed sleep.

Correspondingly, the National Sleep Foundation 2006 ‘Sleep in America’ poll found that adolescents who drank two or more caffeinated beverages each day were more likely to have insufficient sleep on school nights, and think they have a sleep problem, than those who drank one beverage or fewer.

We don’t need no early morning classes

School-based interventions are now underway that aim to improve teenage sleep. Sleep education programmes inform teenagers about the lifestyle factors that may be affecting their sleep and how they can improve sleep hygiene.

There is also a movement to delay school start times to better suit the adolescent clock by giving teenagers the opportunity to sleep at hours more aligned with their chronotype and reduce their social jetlag.

Given all the research, one could suggest that “early to bed, later to rise, may help the teen be healthy, wealthy and wise” would be a better amendment to the age-old quote for our average teenager.

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References

Chang, A.M., Aeschbach, D., Duffy, J.F. and Czeisler, C.A., 2015. Evening use of light-emitting eReaders negatively affects sleep, circadian timing, and next-morning alertness. Proceedings of the National Academy of Sciences, 112(4), pp.1232-1237.

Twenge, J.M., Krizan, Z. and Hisler, G., 2017. Decreases in self-reported sleep duration among US adolescents 2009–2015 and association with new media screen time. Sleep medicine, 39, pp.47-53.

Early to bed and early to rise… makes a teen healthy, wealthy and wise? (Part 1)

By Gaby Illingworth, Rachel Sharman & Russell Foster; @OxTeensleep, @gabyillingwort1, @DrRachelSharman, @OxSCNi

Teenagers are well-known for routinely staying up late and then having a long lie-in. Sometimes this is put down to laziness or their transition from childhood into ‘Kevin the Teenager’.

However, there are biological reasons which help explain why teenagers are late to bed and late to rise, and why they might not actually be getting enough sleep to make them healthy, wealthy, and wise.

Created by Matteo Farinella

Sleep matters. A wealth of evidence supports the importance of sleep for our physical, mental, and emotional functioning. Insufficient sleep has been linked to problems with attention, creativity, memory and academic performance, as well as increased impulsivity, and difficulties with mood regulation.

Sleep: a double-act

Sleep is driven by two processes working in tandem: the circadian rhythm and the drive for sleep (sleep homeostat).

The circadian rhythm is a roughly 24-hour cycle of changes in physiology and behaviour, generated inside our bodies. These rhythms come from certain genes being turned on and off (called clock genes) in almost all cells throughout the body. The master clock, (the suprachiasmatic nucleus in the brain), coordinates the rhythms within these cellular clocks.

The second system involves a balancing (homeostatic) process. Put simply, the longer you have been awake, the greater the need for sleep will become. The drive for sleep is thought to stem from a build-up of various chemicals (in the brain) while we are awake. For example, adenosine is a building block of our body’s energy currency (ATP), so it builds up as a consequence of energy use in the brain. Adenosine inhibits wake-promoting neurons and stimulates sleep-promoting neurons. As we sleep, adenosine is cleared and sleep pressure reduces.

Sometimes the two systems oppose each other. For example, we would feel very sleepy mid-afternoon due to increasing sleep pressure if it were not for the circadian drive for wakefulness.

Sleep occurs when the circadian drive for wakefulness ends and the drive for sleep kicks in. Then when the ‘sleep debt’ you have accumulated during the day has been re-paid (and so sleep pressure is reduced), and the circadian drive for wakefulness is sufficiently strong, we wake up.

Why some people don’t like mornings

Some of us love to burn the midnight oil, while others schedule in regular morning runs. The technical term for your preferred sleep/wake timing is chronotype, what we colloquially refer to as being an owl or a lark. You are owl if your biological clock runs slower and a lark if it runs faster.

We don’t run on 24 hours

While our day runs on 24 hours, for most of us, our internal clocks don’t. Therefore, our internal clock needs to be adjusted daily by external time cues such as light intensity. The master biological clock receives light signals direct from cells in the retina, which are most sensitive to blue light.

Dusk triggers the production of melatonin (the ‘vampire hormone’). Although not a sleep-inducing hormone, melatonin serves as a cue for rest in humans, with levels increasing as we approach sleep and remaining high during the course of the night.

In contrast, dawn light suppresses melatonin levels. The circadian clock responds differently to light depending on the timing of exposure, so that morning light advances the clock (making us get up earlier) and evening light delays the clock (making us get up later the next day).

As well as playing a role in sleep regulation via the circadian clock, light affects how alert you feel. You may have noticed that bright light increases your alertness, so relatively bright light before bedtime will increase the likelihood that you will feel sleepier later.

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Stay tuned for next week’s blog about how changes in these systems affect teenage sleep.