Ruminiclostridium 5, Parabacteroides distasonis, and bile acid profile are modulated by prebiotic diet and associate with facilitated sleep/clock realignment after chronic disruption of rhythms

• Published in: Brain, behavior, and immunity behavior, and immunity, 2021-10, Vol.97, p.150-166
• Main Authors: Thompson, Robert S., Gaffney, Michelle, Hopkins, Shelby, Kelley, Tel, Gonzalez, Antonio, Bowers, Samuel J., Vitaterna, Martha Hotz, Turek, Fred W., Foxx, Christine L., Lowry, Christopher A., Vargas, Fernando, Dorrestein, Pieter C., Wright, Kenneth P., Knight, Rob, Fleshner, Monika
• Format: Article
• Language: English
• Subjects: Animals; Bacteroidetes; Bile acid; Bile Acids and Salts; Cholic acid; Chromatography, Liquid; Circadian; Circadian Rhythm; Clostridium leptum; Diet; Galactooligosaccharide; Male; Parabacteroides distasonis; Polydextrose; Prebiotic; Prebiotics; Rats; Rats, Sprague-Dawley; RNA, Ribosomal, 16S - genetics; Ruminiclostridium 5; Sleep; Tandem Mass Spectrometry; Taurocholic acid; Temperature
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/j.bbi.2021.07.006

•Prebiotics alter the gut microbiome.•Prebiotics increase P. distasonis, Ruminiclostridium 5, and C. leptum.•Prebiotics and circadian disruption (CDR) modulate bile acids.•Prebiotics facilitate realignment of core body temperature (CBT) and sleep to CDR.•Changes in Ruminiclostridium 5 and taurocholic acid relate to CBT and sleep changes. Chronic disruption of rhythms (CDR) impacts sleep and can result in circadian misalignment of physiological systems which, in turn, is associated with increased disease risk. Exposure to repeated or severe stressors also disturbs sleep and diurnal rhythms. Prebiotic nutrients produce favorable changes in gut microbial ecology, the gut metabolome, and reduce several negative impacts of acute severe stressor exposure, including disturbed sleep, core body temperature rhythmicity, and gut microbial dysbiosis. In light of previous compelling evidence that prebiotic diet broadly reduces negative impacts of acute, severe stressors, we hypothesize that prebiotic diet will also effectively mitigate the negative impacts of chronic disruption of circadian rhythms on physiology and sleep/wake behavior. Male, Sprague Dawley rats were fed diets enriched in prebiotic substrates or calorically matched control chow. After 5 weeks on diet, rats were exposed to CDR (12 h light/dark reversal, weekly for 8 weeks) or remained on undisturbed normal light/dark cycles (NLD). Sleep EEG, core body temperature, and locomotor activity were recorded via biotelemetry in freely moving rats. Fecal samples were collected on experimental days –33, 0 (day of onset of CDR), and 42. Taxonomic identification and relative abundances of gut microbes were measured in fecal samples using 16S rRNA gene sequencing and shotgun metagenomics. Fecal primary, bacterially modified secondary, and conjugated bile acids were measured using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Prebiotic diet produced rapid and stable increases in the relative abundances of Parabacteroides distasonis and Ruminiclostridium 5. Shotgun metagenomics analyses confirmed reliable increases in relative abundances of Parabacteroides distasonis and Clostridium leptum, a member of the Ruminiclostridium genus. Prebiotic diet also modified fecal bile acid profiles; and based on correlational and step-wise regression analyses, Parabacteroides distasonis and Ruminiclostridium 5 were positively associated with each other and negatively associated with secondary and conjugated bile ac