The gut-sleep-brain axis: Targeting the gut microbiota and sleep quality by individualized non-pharmaceutical approaches to promote healthy ageing
Lead Research Organisation:
University of East Anglia
Department Name: Health Sciences
Abstract
Our ultimate vision is to develop an intelligent sleep enhancement platform (ISEP) that would ultimately target the promotion of healthy longevity that is broadly accessible, sustainable, avoids pharmaceutical agents and has a range of solutions tailored for various needs and users ranging from health practitioners, through care homes to finally end users (e.g. people with sleep problems and their family members).
In contrast with other existing online platforms that serve similar purposes, ISEP would target the older population and would not anchor to one type of intervention (e.g. CBTi), which has limited efficacy in older people, but build on the combinations of cutting edge innovative approaches such as the modulation of gut health, brain electric activity in sleep, as well as psychological/behaviour approaches (e.g. CBTi, mindfulness).
We believe that the future of health technology lies with personalised interventions that predict efficacious intervention based on individual features, reliably monitor physiological changes and provide intervention adjustment in real-time or nearly real-time. For this to happen the quality of monitoring/data acquisition, data analysis, feature extraction and the range of interventions all need progress. Our proposal will address some of these aspects.
Based on the feasibility and effect size results from the current study we plan to pursue further research to improve the technology including other dietary supplements and non-pharmaceutical methods to improve sleep with similar or better features, optimise the dosage, timing and length of administration and reliably track impact.
Finally, we aim to develop broadly accessible online applications that will provide individualised guidance on a range of interventions adjusted to individual needs and with the best predictable outcome taking into account accessibility, affordability and possible side effects. This tool will not only help both the primary and secondary health care professionals but the everyday end user as well.
Finally, by improving sleep our proposed approach could be employed as a preventative treatment strategy and prospectively lower economic and non-economic costs of treating and caring for individuals with dementia. Prevention is key for improving the quality of life in later stages of life and sleep and diets are two important contributors in this strategy.
In contrast with other existing online platforms that serve similar purposes, ISEP would target the older population and would not anchor to one type of intervention (e.g. CBTi), which has limited efficacy in older people, but build on the combinations of cutting edge innovative approaches such as the modulation of gut health, brain electric activity in sleep, as well as psychological/behaviour approaches (e.g. CBTi, mindfulness).
We believe that the future of health technology lies with personalised interventions that predict efficacious intervention based on individual features, reliably monitor physiological changes and provide intervention adjustment in real-time or nearly real-time. For this to happen the quality of monitoring/data acquisition, data analysis, feature extraction and the range of interventions all need progress. Our proposal will address some of these aspects.
Based on the feasibility and effect size results from the current study we plan to pursue further research to improve the technology including other dietary supplements and non-pharmaceutical methods to improve sleep with similar or better features, optimise the dosage, timing and length of administration and reliably track impact.
Finally, we aim to develop broadly accessible online applications that will provide individualised guidance on a range of interventions adjusted to individual needs and with the best predictable outcome taking into account accessibility, affordability and possible side effects. This tool will not only help both the primary and secondary health care professionals but the everyday end user as well.
Finally, by improving sleep our proposed approach could be employed as a preventative treatment strategy and prospectively lower economic and non-economic costs of treating and caring for individuals with dementia. Prevention is key for improving the quality of life in later stages of life and sleep and diets are two important contributors in this strategy.
Publications
| Description | Age-related neurodegenerative diseases are a growing societal burden with numerous repercussions. Lifestyle and environmental factors play a key role in their development, with sleep quality playing a major role. Pharmaceutical interventions targeting the improvement of sleep quality have multiple limitations starting from numerous side effects to the development of tolerance. Given that 1/3 of the UK population is sleep deprived, non-pharmaceutical strategies to improve sleep quality in older adults are of paramount importance. Limited evidence had shown that Saffron (Crocus sativus) could improve self-reported sleep and affect the gut microbiota. However, the effect of saffron on sleep quality through the modulation of the microbiome was currently lacking. Neither the effects of Saffron intake on objective sleep quality had been measured. To address this knowledge gap we have run a double-blinded randomised placebo-controlled (RCT) study (n=52) in older adults (65 years old) with sleep insomnia symptoms. Participants received either a placebo or a saffron extract (30 mg) for 4 weeks combined with enhanced sleep education (ESE). Sleep quality was assessed both subjectively through questionnaires [Epworth Sleepiness scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Karolinska Sleepiness scale (KSS), and Insomnia Severity Index (ISI)] and objectively through a portable EEG device (Dreem 3). We also studied the feasibility of the Dreem3 device to measure sleep in older people with insomnia across multiple days. Faecal samples were collected pre-and post-intervention to track changes in microbiome composition. Saffron intake improved daytime sleepiness as measured by the EES (p<0.05) and self-reported sleep quality as measured by PSQI (p<0.01) scores with better sleep efficiency observed in females (p= 0.021). Changes in sleep quality were paralleled with an increase in the genus Faecalibacterium, a bacteria previously reported to improve circadian disruptions. There were no significant changes in objectively measured sleep but trends pointed towards an improved sleep quality (i.e., sleep efficiency) and decreased time spent awake during the night in the saffron group. Our study also showed that using the Dreem3 device is a feasible tool to objectively measure sleep in the home environment in the older age group with sleep problems. These results are promising since polypharmacy is a significant problem in elderly patients. This study provides further evidence for the effectiveness of bioactive compounds in improving sleep quality and gut health in older adults. Some further analyses are in the pipeline looking at quantitative features of sleep quality based on the mathematical analysis of the sleep EEG and using machine learning algorithms to identify which are the features that best differentiate responders from non-responders. This will finaly help us develope ISEP (the Individualized Sleep Enhancement Platform) |
| Exploitation Route | Although our study was designed and funded as a pilot study it still had an ambitious experimental research design and was a registered randomized clinical trial. Results indicate that using the Dreem3 device is a feasible tool to objectively measure sleep in the home environment in the older age group with sleep problems. Therefore Dreem3 can be used in larger clinical trials in the future as a reliable tool to measure objective sleep quality in old age patients living with insomnia. Our study provided evidence that Saffron has the potential to improve self-reported sleep quality, particularly in older females with insomnia. Although there were limited non-significant effects on objectively measured sleep quality the results were consistent with the hypothesis of sleep quality improvement. In order to assess the significant effects of Saffronon objectively measured sleep in older adults with insomnia future clinical trial studies should consider using Saffron for a longer period and in a larger sample size. Our results overall suggest that Saffron could be particularly helpful in post-menopausal women who often report self-reported sleep problems. |
| Sectors | Healthcare |
| Description | High accuracy naturalistic sleep quality tracking in older adults to individualize innovative sleep treatment |
| Amount | £5,000 (GBP) |
| Organisation | University of East Anglia |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 01/2022 |
| End | 07/2022 |
| Title | Gut-Sleep study 16S rRNA raw reads |
| Description | Gut 16s rRNA amplicon sequencing Raw sequence reads |
| Type Of Material | Database/Collection of data |
| Year Produced | 2023 |
| Provided To Others? | Yes |
| Impact | 16S rRNA sequences have been deposited on "Sequence Read Archives" with a BioProject accession number PRJNA998744. This dataset is embargoed until until 31 august 2024 to allow full use of the data for publication of the results. Following the embargoed period the dataset will fall in the public domain and may be accessed by other researchers for further analysis |
| URL | https://dataview.ncbi.nlm.nih.gov/objects?linked_to_id=PRJNA998701&archive=biosample |
| Description | Collaboration with food-tech company (Activ'Inside) |
| Organisation | Activ'Inside |
| Country | France |
| Sector | Private |
| PI Contribution | We have established a collaboration with an independent French health food-tech company (Activ'Inside) specialized in the development, production and marketing of natural active ingredients, mainly from grape and saffron. We will run a human intervention study aiming at investigating the effect of nutrition ( a food supplement produced by Activ'Inside containing saffron) versus enhanced sleep education designed by our group on sleep quality. We will provide further evidence regarding the way nutrition can affect sleep quality through the modulation of the gut microbiota. The use of this product is essential to attain this goal and will generate novel data. The company will benefit from the information whether their saffron product can positively modulate sleep quality in healthy elderly. |
| Collaborator Contribution | Activ'Inside has provide the food supplements including the saffron extracts (Saffr'Inside) as the active component and the placebo which was used as the investigational product in our study free of charge. They have developed the studied food supplement and the placebo specifically for our study in the form of gummies and not pills. They have provided the products with food safety certification and microbiological assessments. Activ'Inside also performed the randomisation for our study. The study has been registered on clinical trial.gov (https://clinicaltrials.gov/ct2/show/NCT05315986) |
| Impact | The study has been completed recently and we have been working on the data analysis and preparing the manuscript. This study has been a multidisciplinary research project involving sleep neurophysiology, cognitive psychology, microbiology related to the microbiome analysis and bioinformatics/statistics. |
| Start Year | 2021 |
| Title | Enhanced Sleep Education (ESE) |
| Description | The Enhanced Sleep Education (ESE) intervention is a psychoeducation-based intervention which combines several different previously established sleep interventions into one 15-minute presentation. The intervention discusses elements of sleep education, sleep hygiene, behavioural theories, and mindfulness. ESE provides information to help individuals better understand the biological, environmental, and psychological factors that influence their sleeping patterns and recommendations to help them improve their sleep quality and duration. |
| Type | Therapeutic Intervention - Psychological/Behavioural |
| Current Stage Of Development | Small-scale adoption |
| Year Development Stage Completed | 2022 |
| Development Status | Under active development/distribution |
| Impact | This product has been developed but the first feasibility and acceptability trial has just started. |
| Description | Abstract and poster presentation at the European Sleep Research Congress, Seville, September 2024 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | A member of the research team, MS Leonie LANG, presented the results of this research at the European Sleep Research Conference, and the abstract has also been published. 'Lang, Leonie, et al. "Therapeutic effects of saffron (Crocus Sativus) on objective sleep quality and gut microbiome diversity in older adults with sleep complaints." JOURNAL OF SLEEP RESEARCH. Vol. 33. 111 RIVER ST, HOBOKEN 07030-5774, NJ USA: WILEY, 2024.' |
| Year(s) Of Engagement Activity | 2024 |
| Description | Lifespan Health Research Centre presentation |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Other audiences |
| Results and Impact | This was a presentation on the study and the results given to an academic audience from UEA that also included clinical practitioners. |
| Year(s) Of Engagement Activity | 2024 |
| Description | Oral presentation at the Food Bioactive and Health Conference, Pragues 18-23 September 2023 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | Oral presentation of the outcome of the study at the Food Bioactive and Health Conference, held in Prague September 18-21, 2023. This presentation has sparked questions from the audience, and researchers came to ask further information after the talk |
| Year(s) Of Engagement Activity | 2023 |
| URL | https://fbhc2023.com/ |
| Description | Public talk |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | We organized an open day for our Sleep and Brain Research Unit to celebrate World Sleep Day 2025. We invited students, university staff, the general public, and the media to visit us and learn more about sleep research at UEA through a series of free talks, including a presentation of our research findings from this project funded by UKRI. |
| Year(s) Of Engagement Activity | 2025 |
| URL | https://www.uea.ac.uk/about/news/article/uea-sleep-lab-opens-doors-for-world-sleep-day |
| Description | Talk at a local research conference at UEA |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Postgraduate students |
| Results and Impact | I delivered a research talk at the MSc Research Conference organized for PT, OT, and Dietetics students at UEA. The talk included the presentation of results from this UKRI funded study, which has also been submitted for publication to the Journal, Food and Function. |
| Year(s) Of Engagement Activity | 2025 |
| Description | World Sleep Day - Sleep and Brain Research Open Day - 2023 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | We have organised an event advertised broadly within and outside the university to mark the World Sleep Day and increase public awareness of the importance of sleep for health. The event was linked to an open day of the Sleep and Brain Research Unit at UEA allowing staff members and the public to visit the sleep lab and learn about the way we use to measure sleep and attend to presentations on the role of sleep in development and ageing with a particular focus on the current sleep and gut health study. The event involved speakers across the university including academic staff members and PGR students. |
| Year(s) Of Engagement Activity | 2023 |
| URL | https://my.uea.ac.uk/news/-/article/uea-sleep-lab-open-day-this-friday |