Upper small intestine microbiome in obesity and related metabolic disorders: A new field of investigation.

The study of the gut microbiome holds great promise for understanding and treating metabolic diseases, as its functions and derived metabolites can influence the metabolic status of the host. While research on the fecal microbiome has provided valuable insights, it tells us only part of the story. This limitation arises from the substantial variations in microorganism distribution throughout the gastrointestinal tract due to changes in physicochemical conditions. Thus, relying solely on the fecal microbiome may not be sufficient to draw comprehensive conclusions about metabolic diseases. The proximal part of the small intestine, particularly the jejunum, indeed, serves as the crucial site for digestion and absorption of nutrients, suggesting a potential role of its microbiome in metabolic regulation. Unfortunately, it remains relatively underexplored due to limited accessibility. This review presents current evidence regarding the relationships between the microbiome in the upper small intestine and various phenotypes, focusing on obesity and type 2 diabetes, in both humans and rodents. Research on humans is still limited with variability in the population and methods used. Accordingly, to better understand the role of the whole gut microbiome in metabolic diseases, studies exploring the human microbiome in different niches are needed.

Protein supplementation changes gut microbial diversity and derived metabolites in subjects with type 2 diabetes.

High-protein diets are promoted for individuals with type 2 diabetes (T2D). However, effects of dietary protein interventions on (gut-derived) metabolites in T2D remains understudied. We therefore performed a multi-center, randomized-controlled, isocaloric protein intervention with 151 participants following either 12-week high-protein (HP; 30Energy %, N = 78) vs. low-protein (LP; 10 Energy%, N = 73) diet. Primary objectives were dietary effects on glycemic control which were determined via glycemic excursions, continuous glucose monitors and HbA1c. Secondary objectives were impact of diet on gut microbiota composition and -derived metabolites which were determined by shotgun-metagenomics and mass spectrometry. Analyses were performed using delta changes adjusting for center, baseline, and kidney function when appropriate. This study found that a short-term 12-week isocaloric protein modulation does not affect glycemic parameters or weight in metformin-treated T2D. However, the HP diet slightly worsened kidney function, increased alpha-diversity, and production of potentially harmful microbiota-dependent metabolites, which may affect host metabolism upon prolonged exposure.

Lateralized rhythmic acoustic stimulation during daytime NREM sleep enhances slow waves.

Slow wave sleep (SWS) is characterized by the predominance of delta waves and slow oscillations, reflecting the synchronized activity of large cortical neuronal populations. Amongst other functions, SWS plays a crucial role in the restorative capacity of sleep. Rhythmic acoustic stimulation (RAS) during SWS has been shown a cost-effective method to enhance slow wave activity. Slow wave activity can be expressed in a region-specific manner as a function of previous waking activity. However, it is unclear whether slow waves can be enhanced in a region-specific manner using RAS. We investigated the effects of unilaterally presented rhythmic acoustic sound patterns on sleep electroencephalographic (EEG) oscillations. Thirty-five participants received during SWS 12-second long rhythmic bursts of pink noise (at a rate of 1 Hz) that alternated with non-stimulated, silent periods, unilaterally delivered into one of the ears of the participants. As expected, RAS enhanced delta power, especially in its low-frequency components between 0.75 and 2.25 Hz. However, increased slow oscillatory activity was apparent in both hemispheres regardless of the side of the stimulation. The most robust increases in slow oscillatory activity appeared during the first 3-4 seconds of the stimulation period. Furthermore, a short-lasting increase in theta and sigma power was evidenced immediately after the first pulse of the stimulation sequences. Our findings indicate that lateralized RAS has a strong potential to globally enhance slow waves during daytime naps. The lack of localized effects suggests that slow waves are triggered by the ascending reticular system and not directly by specific auditory pathways.