Gut microbiome composition and functionality impact the responsiveness to a dairy-based product containing galacto-oligosaccharides for improving sleep quality in adults.

Sleep quality and duration can be impacted by diet, and has been linked to gut microbiota composition and function as the result of communication via the microbiota-gut-brain axis. As one strategy to improve sleep quality could be through the modulation of the gut microbiome, we assessed the effects of a dairy-based product containing whey protein, galacto-oligosaccharides, tryptophan, vitamins and minerals after a 3 weeks intervention on gut microbiota composition and (gut-brain related) functions on basis of 67 healthy subjects with moderate sleep disturbances. Associations of the gut microbiota with sleep quality and with response/non-response to the treatment were revealed by shotgun metagenomics sequencing of faecal DNA samples, and subsequent analyses of microbiota taxonomy and generic functionality. A database of manually curated Gut-Brain Modules (GBMs) was applied to analyse specific microbial functions/pathways that have the potential to interact with the brain. A moderate discriminating effect of the DP treatment on gut microbiota composition was revealed which could be mainly attributed to a decrease in Pseudomonas resinovorans, Flintibacter sp. KGM00164, Intestinimonas butyriciproducens, and Flavonifractor plautii. As interindividual variance in microbiota composition could have given rise to a heterogenous responsiveness of the subjects in the intervention group, we zoomed in on the differences between responders and non-responders. A significant difference in baseline microbiota composition between responders and non-responders was apparent, showing lower Bifidobacterium longum and Bifidobacterium adolescentis, and higher Faecalibacterium prausnitzii relative abundances in responders. The findings provide leads with respect to the effectiveness and potential underlying mechanisms of mode of action in sleep improvement that could support future nutritional interventions to aid sleep improvement.

Probiotics, prebiotics and postbiotics for better sleep quality: a narrative review.

There is a growing prevalence of sleep problems and insomnia worldwide, urging the development of new treatments to tackle this increase. Several studies have suggested that the gut microbiome might influence sleep quality. The gut microbiome affects the host's health via the production of metabolites and compounds with neuroactive and immunomodulatory properties, which include short-chain fatty acids, secondary bile acids and neurotransmitters. Several of these metabolites and compounds are independently known as wakefulness-promoting (serotonin, epinephrine, dopamine, orexin, histamine, acetylcholine, cortisol) or sleep-promoting (gamma-aminobutyric acid, melatonin). The primary aim of this review was to evaluate the potential of pro-, pre- and postbiotic treatments to improve sleep quality. Additionally, we aimed to evaluate whether each of the treatments could ameliorate stress and anxiety, which are known to bidirectionally correlate with sleep problems. Lastly, we provided a mechanistic explanation for our findings. A literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar to compare all human trials that met our inclusion criteria and were published before November 2021. We furthermore discussed relevant findings from animal experiments to provide a mechanistic insight. While several studies found that sleep latency, sleep length, and cortisol levels improved after pro-, pre- or postbiotic treatment, others did not show any significant improvements for sleep quality, stress, or anxiety. These discrepancies can be explained by between-study variations in study designs, study populations, treatments, type and level of distress, and sex differences. We conclude that the trials discussed provide some evidence for prebiotics, postbiotics, and traditional probiotics, such as those belonging to lactobacilli and bifidobacteria, to improve sleep quality and stress, but stronger evidence might be found in the future after implementing the methodological adjustments that are suggested in this review.

Deficient mismatch repair system in patients with sporadic advanced colorectal cancer.

A deficient mismatch repair system (dMMR) is present in 10-20% of patients with sporadic colorectal cancer (CRC) and is associated with a favourable prognosis in early stage disease. Data on patients with advanced disease are scarce. Our aim was to investigate the incidence and outcome of sporadic dMMR in advanced CRC. Data were collected from a phase III study in 820 advanced CRC patients. Expression of mismatch repair proteins was examined by immunohistochemistry. In addition microsatellite instability analysis was performed and the methylation status of the MLH1 promoter was assessed. We then correlated MMR status to clinical outcome. Deficient mismatch repair was found in only 18 (3.5%) out of 515 evaluable patients, of which 13 were caused by hypermethylation of the MLH1 promoter. The median overall survival in proficient MMR (pMMR), dMMR caused by hypermethylation of the MLH1 promoter and total dMMR was 17.9 months (95% confidence interval 16.2-18.8), 7.4 months (95% CI 3.7-16.9) and 10.2 months (95% CI 5.9-19.8), respectively. The disease control rate in pMMR and dMMR patients was 83% (95% CI 79-86%) and 56% (30-80%), respectively. We conclude that dMMR is rare in patients with sporadic advanced CRC. This supports the hypothesis that dMMR tumours have a reduced metastatic potential, as is observed in dMMR patients with early stage disease. The low incidence of dMMR does not allow drawing meaningful conclusions about the outcome of treatment in these patients.