The gut's impact on a good night's sleep

European consumers feel that getting adequate sleep has the biggest impact on immunity, according to new research from Euromonitor's Voice of the Consumer Health and Nutrition Survey 2021. And globally, consumers feel that mental wellbeing and getting enough sleep are in the top four key definitions of 'being healthy'.

But in the modern world, sleeping well seems increasingly difficult, with up to 25% of global consumers saying it takes them a long time to fall asleep and 30% saying they still feel tired when they wake up.

There is growing evidence that the gut microbiome might influence our general health via the gut-brain axis, and recently studies have hinted at a link between the gut microbiome and sleep quality.

Gut microbiologist Guus Kortman and data scientist Andrei Prodan, from the food research firm Nizo, explore that link, and its potential implications for the nutraceutical and food ingredient industry.

What evidence is there for a link between gut microbiota and sleep?​

Guus Kortman: Over the last 10-15 years, numerous studies have shown that there is a link between the human gut microbiome and our mental and physical health. Sleep is also closely linked to mental and physical health and, in the last five or so years, a handful of studies have focused explicitly on gut microbiome activity and sleep. These include in vitro​ studies as well as those using animal and human subjects.

The picture from these studies is not entirely clear cut, with some results seeming to conflict with others. For example, one study found that partial sleep deprivation can alter the gut microbiome composition in as little as 48 hours while another suggested that longer periods of sleep deprivation don’t affect the microbiome.

But overall, there is credible evidence for a close relationship between sleep quality and factors such as reduced gut microbiome diversity and inflammation markers. Meanwhile, in vitro​ studies have linked particular gut bacteria strains with neurotransmitters or hormones that are known to influence sleep such as serotonin.

Has this research identified any promising candidates for promoting good sleep?​

GK: As I mentioned, good sleep seems to correlate with a healthy diversity in the gut microbiome. But a number of specific bacteria have also been linked with good sleep. These include various Bifidobacteria​ and Lactobacilli​ in probiotic formulations, as well as various members of the gut microbiome. ​There have been studies done on these and other strains as probiotics, but the results are somewhat clouded as factors such as the subjects’ diets and the timing of the probiotic intake weren’t always well controlled. And the evidence does suggest that these factors could be important to the scale of the effect.

The complementary approach of promoting natural growth of the desired bacteria in the gut through prebiotics and other nutritional components is also being explored. One of the most mature of these investigations is into galacto-oligosaccharides (GOS), an area NIZO has itself been active in, for example, collaborating with researchers from FrieslandCampina and Philips to study how a product based on whey protein and GOS affected sleep quality, stress and gut microbiota​. Indeed, the first product targeting sleep quality based on GOS, in combination with sleep-promoting amino acids, appeared on the market earlier this year.

Where does research in this area go next?​

GK: There are still many open questions in this area that need exploring. Perhaps the biggest of these is to identify the most important mechanisms involved in the relationship between the gut microbiome and sleep. For example, is the link mediated through inflammation, influencing circadian rhythms, the production of neurotransmitters by the bacteria directly, or the action of bacterial metabolites? And what is the role of the vagus nerve, which runs between the gut and the brain, in this interaction?

To answer these questions, we need more, larger and better controlled human studies that measure sleep quality directly as an outcome of probiotic and prebiotic intake. At the same time, there are a number of next-generation (butyric acid producing) probiotics, such as Clostridiales and Akkermansia, and prebiotics that should be investigated.

Such studies seem to rely on measuring a subject’s microbiome. How do we do that?​

Andrei Prodan: Traditionally, studying the microbiome has focused on measuring its composition: identifying and counting the different bacterial strains in the gut. But recent developments in gene sequencing technology, bioinformatics and computing power are allowing us to gain more insight into the functionality of the bacteria in the gut microbiome. So, we can see not just which and how many bacteria are present, but what they are doing in the gut and how they may impact health factors such as sleep quality.

SL: What is the practical benefit for the nutraceutical industry?​

AP: It will allow much faster screening and identification of possible new probiotics that target specific health benefits. For example, by sequencing and analysing the genomes of bacteria that are known to affect sleep quality, we are able to create what are known as profile Hidden Markov Models (pHMMs). These are mathematical patterns that we can use to recognise sequences in the genomes of unknown bacteria that will also impact sleep quality.

As a result, you would be able to screen thousands of bacteria in silico​ to find the few most promising candidates to take into in vitro​ and in vivo​ studies. This approach could dramatically streamline the identification of new, targeted probiotic strains and the development of new nutraceutical products.