Age-related patterns of microbial dysbiosis in multiplex inflammatory bowel disease families.

OBJECTIVE: IBD is characterised by dysbiosis, but it remains unclear to what extent dysbiosis develops in unaffected at-risk individuals. To address this, we investigated age-related patterns of faecal and serum markers of dysbiosis in high-risk multiplex IBD families (two or more affected first-degree relatives). DESIGN: Faecal and serum samples were collected from multiplex IBD and control families (95 IBD, 292 unaffected, 51 controls). Findings were validated in independent cohorts of 616 and 1173 subjects including patients with IBD, infants born to mothers with IBD and controls. 16S rRNA gene sequencing and global untargeted metabolomics profiling of faeces and serum were performed. RESULTS: Microbial and metabolomic parameters of dysbiosis progressively decreased from infancy until age 8. This microbial maturation process was slower in infants born to mothers with IBD. After age 15, dysbiosis steadily increased in unaffected relatives throughout adulthood. Dysbiosis was accompanied by marked shifts in the faecal metabolome and, to a lesser extent, the serum metabolome. Faecal and serum metabolomics dysbiosis indices were validated in an independent cohort. Dysbiosis was associated with elevated antimicrobial serologies but not with faecal calprotectin. Dysbiosis metrics differentiated IBD from non-IBD comparably to serologies, with a model combining calprotectin, faecal metabolomics dysbiosis index and serology score demonstrating highest accuracy. CONCLUSION: These findings support that dysbiosis exists as a pre-disease state detectable by faecal and serum biomarkers for IBD risk prediction. Given the expansion of disease-modifying agents and non-invasive imaging, the indices developed here may facilitate earlier diagnoses and improved management in at-risk individuals.

Longitudinal monitoring of IL-6 and CRP in inflammatory bowel disease using IBD-AWARE.

There are limitations to monitoring modalities for chronic inflammatory conditions, including inflammatory bowel disease (IBD). Wearable devices are scalable mobile health technology that present an opportunity to monitor markers that have been linked to worsening, chronic inflammatory conditions and enable remote monitoring. In this research article, we evaluate and demonstrate a proof-of-concept wearable device to longitudinally monitor inflammatory and immune markers linked to IBD disease activity in sweat compared to expression in serum. Sixteen participants with an IBD-related hospital admission and a C-reactive protein (CRP) > 5 µg/mL were followed for up to 5 days. The sweat sensing device also known as IBD AWARE was worn to continuously measure CRP and interleukin-6 (IL-6) in the sweat of participants via electrochemical impedance spectroscopy. Serum samples were collected daily. A linear relationship between serum and sweat readings for CRP and IL-6 was demonstrated based on individual linear correlation coefficients. Pooled CRP and IL-6 serum-to-sweat ratios demonstrated improving correlation coefficients as serum cutoffs decreased. Between the first and last day of observation, significant and non-significant trends in serum CRP and IL-6 were observed in the sweat. Comparison of sweat measurements between the subjects with active IBD and 10 healthy subjects distinguished an inflamed and uninflamed state with an AUC of 0.85 (95% CI: 0.68-1.00) and a sensitivity and specificity of 82% and 70% at a CRP cutoff of 938.9 pg/mL. IBD AWARE wearable device holds promise in longitudinally monitoring individuals with IBD and other inflammatory diseases.

Longitudinal assessment of sweat-based TNF-alpha in inflammatory bowel disease using a wearable device.

Wearable devices can non-invasively monitor patients with chronic diseases. Sweat is an easily accessible biofluid for continuous sampling of analytes, including inflammatory markers and cytokines. We evaluated a sweat sensing wearable device in subjects with and without inflammatory bowel disease (IBD), a chronic inflammatory condition of the gastrointestinal tract. Participants with an IBD related hospital admission and a C-reactive protein level above 5 mg/L wore a sweat sensing wearable device for up to 5 days. Tumor necrosis factor-alpha (TNF-α) levels were continually assessed in the sweat via the sensor, and daily in the blood. A second cohort of healthy subjects without chronic diseases wore the device for up to 48 h. Twenty-eight subjects were enrolled. In the 16 subjects with IBD, a moderate linear relationship between serum and sweat TNF-α levels was observed (R2 = 0.72). Subjects with IBD were found to have a mean sweat TNF-α level of 2.11 pg/mL, compared to a mean value of 0.19 pg/mL in 12 healthy controls (p < 0.0001). Sweat TNF-α measurements differentiated subjects with active IBD from healthy subjects with an AUC of 0.962 (95% CI 0.894-1.000). A sweat sensing wearable device can longitudinally measure key sweat-based markers of IBD. TNF-α levels in the sweat of subjects with IBD correlate with serum values, suggesting feasibility in non-invasive disease monitoring.

Remote Short Sessions of Heart Rate Variability Biofeedback Monitored With Wearable Technology: Open-Label Prospective Feasibility Study.

BACKGROUND: Heart rate variability (HRV) biofeedback is often performed with structured education, laboratory-based assessments, and practice sessions. It has been shown to improve psychological and physiological function across populations. However, a means to remotely use and monitor this approach would allow for wider use of this technique. Advancements in wearable and digital technology present an opportunity for the widespread application of this approach. OBJECTIVE: The primary aim of the study was to determine the feasibility of fully remote, self-administered short sessions of HRV-directed biofeedback in a diverse population of health care workers (HCWs). The secondary aim was to determine whether a fully remote, HRV-directed biofeedback intervention significantly alters longitudinal HRV over the intervention period, as monitored by wearable devices. The tertiary aim was to estimate the impact of this intervention on metrics of psychological well-being. METHODS: To determine whether remotely implemented short sessions of HRV biofeedback can improve autonomic metrics and psychological well-being, we enrolled HCWs across 7 hospitals in New York City in the United States. They downloaded our study app, watched brief educational videos about HRV biofeedback, and used a well-studied HRV biofeedback program remotely through their smartphone. HRV biofeedback sessions were used for 5 minutes per day for 5 weeks. HCWs were then followed for 12 weeks after the intervention period. Psychological measures were obtained over the study period, and they wore an Apple Watch for at least 7 weeks to monitor the circadian features of HRV. RESULTS: In total, 127 HCWs were enrolled in the study. Overall, only 21 (16.5%) were at least 50% compliant with the HRV biofeedback intervention, representing a small portion of the total sample. This demonstrates that this study design does not feasibly result in adequate rates of compliance with the intervention. Numerical improvement in psychological metrics was observed over the 17-week study period, although it did not reach statistical significance (all P>.05). Using a mixed effect cosinor model, the mean midline-estimating statistic of rhythm (MESOR) of the circadian pattern of the SD of the interbeat interval of normal sinus beats (SDNN), an HRV metric, was observed to increase over the first 4 weeks of the biofeedback intervention in HCWs who were at least 50% compliant. CONCLUSIONS: In conclusion, we found that using brief remote HRV biofeedback sessions and monitoring its physiological effect using wearable devices, in the manner that the study was conducted, was not feasible. This is considering the low compliance rates with the study intervention. We found that remote short sessions of HRV biofeedback demonstrate potential promise in improving autonomic nervous function and warrant further study. Wearable devices can monitor the physiological effects of psychological interventions.