The East Asian gut microbiome is distinct from colocalized White subjects and connected to metabolic health.

East Asians (EAs) experience worse metabolic health outcomes compared to other ethnic groups at lower body mass indices; however, the potential role of the gut microbiota in contributing to these health disparities remains unknown. We conducted a multi-omic study of 46 lean and obese East Asian and White participants living in the San Francisco Bay Area, revealing marked differences between ethnic groups in bacterial richness and community structure. White individuals were enriched for the mucin-degrading Akkermansia muciniphila. East Asian subjects had increased levels of multiple bacterial phyla, fermentative pathways detected by metagenomics, and the short-chain fatty acid end-products acetate, propionate, and isobutyrate. Differences in the gut microbiota between the East Asian and White subjects could not be explained by dietary intake, were more pronounced in lean individuals, and were associated with current geographical location. Microbiome transplantations into germ-free mice demonstrated stable diet- and host genotype-independent differences between the gut microbiotas of East Asian and White individuals that differentially impact host body composition. Taken together, our findings add to the growing body of literature describing microbiome variations between ethnicities and provide a starting point for defining the mechanisms through which the microbiome may shape disparate health outcomes in East Asians.

The community of microbes living in the human gut varies based on where a person lives, in part because of differences in diets but also due to factors still incompletely understood. In turn, this 'microbiome' may have wide-ranging effects on health and diseases such as obesity and diabetes. Many scientists want to understand how differences in the microbiome emerge between people, and whether this may explain why certain diseases are more common in specific populations. Self-identified race or ethnicity can be a useful tool in that effort, as it can serve as a proxy for cultural habits (such as diets) or genetic information. In the United States, self-identified East Asian Americans often have worse 'metabolic health' (e.g. levels of sugar or certain fat molecules in the blood) at a lower weight than those identifying as White. Ang, Alba, Upadhyay et al. investigated whether this health disparity was linked to variation in the gut microbiome. Samples were collected from 46 lean and obese individuals living in the San Francisco Bay Area who identified as White or East Asian. The analyses showed that while the gut microbiome of White participants changed in association with obesity, the microbiomes of East Asian participants were distinct from their White counterparts even at normal weight, with features mirroring what was seen in White individuals in the context of obesity. Although these differences were connected to people's current address, they were not attributable to dietary differences. Ang, Alba, Upadhyay et al. then transplanted the microbiome of the participants into genetically identical mice with microbe-free guts. The differences between the gut microbiomes of White and East Asian participants persisted in recipient animals. When fed the same diet, the mice also gained different amounts of weight depending on the ethnic identity of the microbial donor. These results show that self-identified ethnicity may be an important variable to consider in microbiome studies, alongside other factors such as geography. Ultimately, this research may help to design better, more personalized treatments for an array of conditions.

Prognostic significance of body mass index-adjusted criteria for left ventricular hypertrophy.

Electrocardiographic left ventricular hypertrophy (ECG-LVH) is associated with both cardiovascular and all-cause mortality. Obesity attenuates the sensitivity of several ECG-LVH criteria, so body mass index (BMI) adjusted criteria have been developed. However, the prognostic significance of BMI-adjusted ECG-LVH criteria is not known. This analysis included 7812 participants (59.8 ± 13.4 years, 53% women, 50% non-Hispanic-whites) from the Third National Health and Nutrition Examination Survey. The Cornell criteria (R in aVL + S in V3 ≥ 2800 µV in men or ≥2200 µV in women) and Sokolow-Lyon criteria (S in V1 + R in V5 or R in V6 ≥ 3500 µV) criteria were used for LVH. To account for the effects of obesity, the BMI-adjusted Cornell criteria (product of R in aVL + S in V3 and BMI > 60 400 µV kg m-2 ) and the BMI-adjusted Sokolow-Lyon criteria (add 400 µV if overweight, add 800 µV if obese) were used. Compared to traditional ECG-LVH criteria, more participants met criteria for ECG-LVH with BMI-adjusted Cornell voltage (9.9% vs 2.9%) and BMI-adjusted Sokolow-Lyon (13.1% vs 6.4%) criteria. In multivariable-adjusted Cox proportional hazards models, the BMI-adjusted Sokolow-Lyon criteria performed no better than traditional criteria (HR 1.18, 95% CI 1.06-1.32 for all-cause, HR 1.38, 95% CI 1.17-1.62 for cardiovascular mortality) and the BMI-adjusted Cornell voltage criteria attenuated the association with all-cause (HR 1.16, 95% CI 1.03-1.32) and cardiovascular mortality (HR 1.34, 95% CI 1.13-1.60). Despite potential improvements in the detection of LVH using BMI-adjusted ECG-LVH criteria, adjusting for BMI may result in the loss of prognostic information.

Impact of the Location of ST-T Abnormalities Accompanying Minor Q-Waves on the Definition of Prior Myocardial Infarction.

According to the Fourth Universal Definition of myocardial infarction (MI), the likelihood of a previous MI is increased when ST-T abnormalities exist with minor Q-waves in the same leads. Therefore, we examined whether differences in location of ST-T abnormalities in relation to minor Q-waves as part of the old MI definition impact the prevalence and prognostic significance of MI. This analysis included 7,878 participants with available baseline electrocardiogram (ECG) and follow-up data from the third National Health and Nutrition Examination Survey. Two ECG MI definitions were utilized; both were based on the standards of the Minnesota Code (MC) ECG Classification, and both incorporated major Q-waves but differed in whether major ST-T abnormalities and minor Q waves, as part of the definition, were in the same lead group (Standard MC-MI) or not (Fourth Universal MI). All-cause mortality and cardiovascular disease mortality were ascertained during 14 years (median). We found no difference between baseline prevalence of Standard MC-MI (3.48%; n = 274) and Fourth Universal MI (3.27%; n = 258), p = 0.46. Also, Standard MC-MI and Fourth Universal MI were similarly associated with increased risk of all-cause mortality (hazard ratio [95% confidence interval] 1.64 [1.42 to 1.90] and 1.61 [1.38 to 1.87], respectively; p value for differences in associations = 0.86), and cardiovascular disease mortality (hazard ratio [95% confidence interval] 1.99 [1.61 to 2.48] and 1.94 [1.56 to 2.42], respectively; p value for differences in associations = 0.84). In conclusion, the location of ST-T abnormalities accompanying minor Q-waves does not impact the prevalence or prognostic significance of a prior MI which raise doubts about the clinical impact of considering the location of ST-T in relation to minor Q-waves when defining an old MI.

Effects of Metreleptin on Proteinuria in Patients With Lipodystrophy.

CONTEXT: Patients with lipodystrophy have high prevalence of proteinuria. OBJECTIVE: To assess kidney disease in patients with generalized (GLD) vs partial lipodystrophy (PLD), and the effects of metreleptin on proteinuria in patients with lipodystrophy. DESIGN, SETTING, PATIENTS, INTERVENTION: Prospective, open-label studies of metreleptin treatment in patients with GLD and PLD at the National Institutes of Health. OUTCOME MEASURES: The 24-hour urinary albumin and protein excretion rates, estimated glomerular filtration rate (eGFR), and creatinine clearance (CrCl) were measured at baseline and during up to 24 months of metreleptin treatment. Patients with increases in medications affecting outcome measures were excluded. RESULTS: At baseline, patients with GLD had significantly greater albuminuria, proteinuria, eGFR, and CrCl compared with patients with PLD. CrCl was above the normal range in 69% of patients with GLD and 39% with PLD (P = 0.02). With up to 24 months of metreleptin treatment, there were significant reductions in albuminuria and proteinuria in patients with GLD, but not in those with PLD. No changes in eGFR or CrCl were observed in patients with GLD or PLD during metreleptin treatment. CONCLUSIONS: Patients with GLD had significantly greater proteinuria than those with PLD, which improved with metreleptin treatment. The mechanisms leading to proteinuria in lipodystrophy and improvements in proteinuria with metreleptin are not clear. Hyperfiltration was also more common in GLD vs PLD but did not change with metreleptin.

Context-Dependent Neural Activation: Internally and Externally Guided Rhythmic Lower Limb Movement in Individuals With and Without Neurodegenerative Disease.

Parkinson's disease is a neurodegenerative disorder that has received considerable attention in allopathic medicine over the past decades. However, it is clear that, to date, pharmacological and surgical interventions do not fully address symptoms of PD and patients' quality of life. As both an alternative therapy and as an adjuvant to conventional approaches, several types of rhythmic movement (e.g., movement strategies, dance, tandem biking, and Tai Chi) have shown improvements to motor symptoms, lower limb control, and postural stability in people with PD (1-6). However, while these programs are increasing in number, still little is known about the neural mechanisms underlying motor improvements attained with such interventions. Studying limb motor control under task-specific contexts can help determine the mechanisms of rehabilitation effectiveness. Both internally guided (IG) and externally guided (EG) movement strategies have evidence to support their use in rehabilitative programs. However, there appears to be a degree of differentiation in the neural substrates involved in IG vs. EG designs. Because of the potential task-specific benefits of rhythmic training within a rehabilitative context, this report will consider the use of IG and EG movement strategies, and observations produced by functional magnetic resonance imaging and other imaging techniques. This review will present findings from lower limb imaging studies, under IG and EG conditions for populations with and without movement disorders. We will discuss how these studies might inform movement disorders rehabilitation (in the form of rhythmic, music-based movement training) and highlight research gaps. We believe better understanding of lower limb neural activity with respect to PD impairment during rhythmic IG and EG movement will facilitate the development of novel and effective therapeutic approaches to mobility limitations and postural instability.