Gut microbiota and glucometabolic alterations in response to recurrent partial sleep deprivation in normal-weight young individuals

Abstract

Objective: Changes to the microbial community in the human gut have been proposed to promote metabolic disturbances that also occur after short periods of sleep loss (including insulin resistance). However, whether sleep loss affects the gut microbiota remains unknown.

Methods: In a randomized within-subject crossover study utilizing a standardized in-lab protocol (with fixed meal times and exercise schedules), we studied nine normal-weight men at two occasions: after two nights of partial sleep deprivation (PSD; sleep opportunity 02:45-07:00 h), and after two nights of normal sleep (NS; sleep opportunity 22:30-07:00 h). Fecal samples were collected within 24 h before, and after two in-lab nights, of either NS or PSD. In addition, participants underwent an oral glucose tolerance test following each sleep intervention.

Results: Microbiota composition analysis (V4 16S rRNA gene sequencing) revealed that after two days of PSD vs. after two days of NS, individuals exhibited an increased Firmicutes:Bacteroidetes ratio, higher abundances of the families Coriobacteriaceae and Erysipelotrichaceae, and lower abundance of Tenericutes (all P < 0.05) - previously all associated with metabolic perturbations in animal or human models. However, no PSD vs. NS effect on beta diversity or on fecal short-chain fatty acid concentrations was found. Fasting and postprandial insulin sensitivity decreased after PSD vs. NS (all P < 0.05).

Discussion: Our findings demonstrate that short-term sleep loss induces subtle effects on human microbiota. To what extent the observed changes to the microbial community contribute to metabolic consequences of sleep loss warrants further investigations in larger and more prolonged sleep studies, to also assess how sleep loss impacts the microbiota in individuals who already are metabolically compromised.

Keywords: Bacteroidetes; F:B, Firmicutes:Bacteroidetes (ratio); Firmicutes; HDL, high-density lipoprotein; HOMA-IR, homeostatic assessment model of insulin resistance; Insulin resistance; Intestinal microbiome; LDL, low-density lipoprotein; NS, normal sleep; OGTT, oral glucose tolerance test; OTU, Operational Taxonomic Units; PERMANOVA, permutational analysis of variance; PSD, partial sleep deprivation; SCFA, short-chain fatty acid; Short-chain fatty acid; Sleep restriction; T2DM, type-2 diabetes mellitus; d2, day 2.

Figure 1

(A) High relative abundance of taxa within the phyla Firmicutes, Actinobacteria, and Bacteroidetes was observed across the fecal samples from the PSD (partial sleep deprivation) and normal sleep (NS) condition. Subjects are arbitrarily numbered and clustered along the y-axis based on bacterial phylum composition. (B) In an analysis across samples at the family level, high abundances were observed of Lachnospiraceae, Ruminococcaceae, Bifidobacteriaceae – and to lesser and more variable extent – of Coriobacteriaceae. (C) The microbiome sequencing analysis of samples obtained after sleep and PSD revealed 136 families; firmicutes was the most diverse phylum, containing the greatest number (69) of the classified families. d2, day 2.

Figure 1

(A) High relative abundance of taxa within the phyla Firmicutes, Actinobacteria, and Bacteroidetes was observed across the fecal samples from the PSD (partial sleep deprivation) and normal sleep (NS) condition. Subjects are arbitrarily numbered and clustered along the y-axis based on bacterial phylum composition. (B) In an analysis across samples at the family level, high abundances were observed of Lachnospiraceae, Ruminococcaceae, Bifidobacteriaceae – and to lesser and more variable extent – of Coriobacteriaceae. (C) The microbiome sequencing analysis of samples obtained after sleep and PSD revealed 136 families; firmicutes was the most diverse phylum, containing the greatest number (69) of the classified families. d2, day 2.

Figure 2

Within and across-subject variation tests for alpha diversity for both conditions (normal sleep, NS; vs. partial sleep deprivation, PSD) and time points (baseline vs. day 2 (d2) sample), using Observed and Shannon methods. See Supplementary Table 2 for statistical comparisons.

Figure 3

Glucometabolic values in response to normal sleep (black bar and solid lines) and partial sleep deprivation (white bar and dashed lines) for two consecutive nights. HOMA-IR and Matsuda index in the upper panel were obtained in the fasting state and from an oral glucose tolerance test (OGTT), respectively. Curves for plasma glucose (middle panel) and insulin (lower panel) were obtained from pre and post (up to 120 min) OGTT values. n = 9; *, P < 0.05.