Psychometric Testing of a Food Timing Questionnaire and Food Timing Screener.

BACKGROUND: Circadian rhythms coordinate multiple biological processes, and time of eating is an important entrainer of peripheral circadian clocks, including those in the gastrointestinal tract and liver. Whereas time of eating can be assessed through valid and reliable tools designed to measure nutrient intake (24-h recalls), currently there is no easily administered, valid, and reliable tool designed to specifically assess both time of food intake and sleep. OBJECTIVES: The objective of this study was to test the validity and reliability of 2 questionnaires developed to measure food and sleep-wake timing, the Food Timing Questionnaire (FTQ) and Food Timing Screener (FTS), and the agreement between these 2 tools. METHODS: The content validity of these tools was assessed by an expert panel of 10 registered dietitian nutritionists. Adult volunteers (n = 61) completed both tools to assess internal consistency and test-retest reliability. Criterion-related validity was determined through the association of FTQ and FTS with 2 valid instruments, the Automated Self-Administered 24-hour recall (ASA24®) Dietary Assessment tool and the Munich Chronotype Questionnaire. Agreement between the FTQ and FTS was tested by calculating the Pearson's correlations for both food and sleep-wake timing. RESULTS: The content validity indexes for both tools were >0.80, and internal consistency and test-retest reliability coefficients were >0.50 for all meals and sleep-wake times. Correlation coefficients were >0.40 between both tools and criterion measures of food intake and sleep except for snacks. Correlations between the FTQ and FTS for all eating events and sleep were >0.60 except for snack 1. CONCLUSIONS: Both the FTQ and FTS are valid and reliable instruments for meal timing and sleep. However, further psychometric testing in a more expansive and diverse sample will improve the ability of these tools to accurately assess food timing and sleep and their impact on health outcomes.

Chronotype, social jet lag, sleep debt and food timing in inflammatory bowel disease.

The preference of the sleep/wake cycle can be grouped into categories or chronotypes. Inflammatory bowel disease (IBD) has been linked to poor sleep quality which correlates with disease severity. Social jet lag (SJL) is the difference between sleep timing on work and free days and is a marker for circadian misalignment which has been linked to increased inflammation. We investigated whether chronotype, SJL, sleep debt (SD), and food timing were associated with an IBD specific complications and a lower quality of life. Overall, 191 subjects (115 IBD subjects and 76 healthy controls (HC)) completed the Pittsburgh Sleep Quality Index (PSQI), Morningness-Eveningness Questionnaire (MEQ), Munich ChronoType Questionnaire (MCTQ), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), and a structured Food Timing Questionnaire. Later chronotype (by MEQ) was associated with a worse SIBDQ (r = -0.209; P < 0.05). SJL was increased in IBD at 1.32 h ± 1.03 vs. 1.05 h ± 0.97 in HC, P < 0.05, when adjusted for age. SJL (>2 h) was present in 40% of severe/complicated Crohn's patients (fistulizing or structuring Crohn's or history of Crohn's related surgery) compared to only 16% of uncomplicated Crohn's patients (P < 0.05). Sleep debt was increased in IBD subjects compared to HC at 21.90 m ± 25.37 vs. 11.49 m ± 13.58, P < 0.05. IBD subjects with inconsistent breakfast or dinner times had lower SIBDQ scores (4.78 ± 1.28 vs. 5.49 ± 1.02, P < 0.05; 4.95 ± 0.31 vs. 5.42 ± 0.32, P < 0.05 respectively). In summary, later chronotype, and markers of circadian misalignment (social jet lag, sleep debt, and inconsistent meal timing) were associated with IBD disease specific complications and/or lower quality of life.

A compartmentalized type I interferon response in the gut during chronic HIV-1 infection is associated with immunopathogenesis.

OBJECTIVE(S): Type I interferon (IFN-I) responses confer both protective and pathogenic effects in persistent virus infections. IFN-I diversity, stage of infection and tissue compartment may account for this dichotomy. The gut is a major site of early HIV-1 replication and microbial translocation, but the nature of the IFN-I response in this compartment remains unclear. DESIGN: Samples were obtained from two IRB-approved cross-sectional studies. The first study included individuals with chronic, untreated HIV-1 infection (n = 24) and age/sex-balanced uninfected controls (n = 14). The second study included antiretroviral-treated, HIV-1-infected individuals (n = 15) and uninfected controls (n = 15). METHODS: The expression of 12 IFNα subtypes, IFNß and antiviral IFN-stimulated genes (ISGs) were quantified in peripheral blood mononuclear cells (PBMCs) and colon biopsies using real-time PCR and next-generation sequencing. In untreated HIV-1-infected individuals, associations between IFN-I responses and gut HIV-1 RNA levels as well as previously established measures of colonic and systemic immunological indices were determined. RESULTS: IFNα1, IFNα2, IFNα4, IFNα5 and IFNα8 were upregulated in PBMCs during untreated chronic HIV-1 infection, but IFNß was undetectable. By contrast, IFNß was upregulated and all IFNα subtypes were downregulated in gut tissue. Gut ISG levels positively correlated with gut HIV-1 RNA and immune activation, microbial translocation and inflammation markers. Gut IFN-I responses were not significantly different between HIV-1-infected individuals on antiretroviral treatment and uninfected controls. CONCLUSION: The IFN-I response is compartmentalized during chronic untreated HIV-1 infection, with IFNß being more predominant in the gut. Gut IFN-I responses are associated with immunopathogenesis, and viral replication is likely a major driver of this response.

Effect of cytomegalovirus and Epstein-Barr virus replication on intestinal mucosal gene expression and microbiome composition of HIV-infected and uninfected individuals.

BACKGROUND: HIV-infection is associated with dramatic changes in the intestinal mucosa. The impact of other viral pathogens is unclear. METHODS: One hundred and eight (108) biopsies from left and right colon (n = 79) and terminal ileum (n = 29) were collected from 19 HIV-infected and 22 HIV-uninfected participants. Levels of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) DNA were measured by droplet digital PCR. Mucosal gene expression was measured via multiplex-assay. Microbiome analysis was performed using bacterial 16S-rDNA-pyrosequencing. The effect of CMV and EBV replication on the microbiome composition and mRNA-expression of selected cytokines (IL-6, IFN-γ, IL-1ß, CCL2, IL-8, and IFN-ß1) was evaluated. RESULTS: Overall, CMV and EBV were detected in at least one intestinal site in 60.5 and 78.9% of participants, respectively. HIV-infected individuals demonstrated less detectable CMV (PB = 0.02); CMV was more frequently detected in terminal ileum than colon (PB = 0.05). Detectable EBV was more frequent among HIV-infected (P B= 0.04) without differences by intestinal site. The number of operational taxonomic units did not differ by CMV or EBV detection status. Among HIV-infected participants, higher CMV was only associated with lower relative abundance of Actinobacteria in the ileum (P = 0.03). Presence of CMV was associated with upregulated expression of all selected cytokines in the ileum (all P < 0.02) and higher expression of IL-8 and IFN-ß1 in the colon (all P < 0.05) of HIV-uninfected participants, but not among HIV-infected. EBV had no effect on cytokine expression or microbiome composition whatsoever. CONCLUSION: These results illustrate a complex interplay among HIV-infection, intestinal CMV replication, and mucosal gut environment, and highlight a possible modulatory effect of CMV on the microbial and immune homeostasis.

A compositional look at the human gastrointestinal microbiome and immune activation parameters in HIV infected subjects.

HIV progression is characterized by immune activation and microbial translocation. One factor that may be contributing to HIV progression could be a dysbiotic microbiome. We therefore hypothesized that the GI mucosal microbiome is altered in HIV patients and this alteration correlates with immune activation in HIV. 121 specimens were collected from 21 HIV positive and 22 control human subjects during colonoscopy. The composition of the lower gastrointestinal tract mucosal and luminal bacterial microbiome was characterized using 16S rDNA pyrosequencing and was correlated to clinical parameters as well as immune activation and circulating bacterial products in HIV patients on ART. The composition of the HIV microbiome was significantly different than that of controls; it was less diverse in the right colon and terminal ileum, and was characterized by loss of bacterial taxa that are typically considered commensals. In HIV samples, there was a gain of some pathogenic bacterial taxa. This is the first report characterizing the terminal ileal and colonic mucosal microbiome in HIV patients with next generation sequencing. Limitations include use of HIV-infected subjects on HAART therapy.