Mining the Human Gut Microbiota for Immunomodulatory Organisms.

Within the human gut reside diverse microbes coexisting with the host in a mutually advantageous relationship. Evidence has revealed the pivotal role of the gut microbiota in shaping the immune system. To date, only a few of these microbes have been shown to modulate specific immune parameters. Herein, we broadly identify the immunomodulatory effects of phylogenetically diverse human gut microbes. We monocolonized mice with each of 53 individual bacterial species and systematically analyzed host immunologic adaptation to colonization. Most microbes exerted several specialized, complementary, and redundant transcriptional and immunomodulatory effects. Surprisingly, these were independent of microbial phylogeny. Microbial diversity in the gut ensures robustness of the microbiota's ability to generate a consistent immunomodulatory impact, serving as a highly important epigenetic system. This study provides a foundation for investigation of gut microbiota-host mutualism, highlighting key players that could identify important therapeutics.

Treg cells require Izumo1R to regulate γδT cell-driven inflammation in the skin.

Izumo1R is a pseudo-folate receptor with an essential role in mediating tight oocyte/spermatozoa contacts during fertilization. Intriguingly, it is also expressed in CD4+ T lymphocytes, in particular Treg cells under the control of Foxp3. To understand Izumo1R function in Treg cells, we analyzed mice with Treg-specific Izumo1r deficiency (Iz1rTrKO). Treg differentiation and homeostasis were largely normal, with no overt autoimmunity and only marginal increases in PD1+ and CD44hi Treg phenotypes. pTreg differentiation was also unaffected. Iz1rTrKO mice proved uniquely susceptible to imiquimod-induced, γδT cell-dependent, skin disease, contrasting with normal responses to several inflammatory or tumor challenges, including other models of skin inflammation. Analysis of Iz1rTrKO skin revealed a subclinical inflammation that presaged IMQ-induced changes, with an imbalance of Rorγ+ γδT cells. Immunostaining of normal mouse skin revealed the expression of Izumo1, the ligand for Izumo1R, electively in dermal γδT cells. We propose that Izumo1R on Tregs enables tight contacts with γδT cells, thereby controlling a particular path of skin inflammation.

The transcriptional landscape of αß T cell differentiation.

The differentiation of αßT cells from thymic precursors is a complex process essential for adaptive immunity. Here we exploited the breadth of expression data sets from the Immunological Genome Project to analyze how the differentiation of thymic precursors gives rise to mature T cell transcriptomes. We found that early T cell commitment was driven by unexpectedly gradual changes. In contrast, transit through the CD4(+)CD8(+) stage involved a global shutdown of housekeeping genes that is rare among cells of the immune system and correlated tightly with expression of the transcription factor c-Myc. Selection driven by major histocompatibility complex (MHC) molecules promoted a large-scale transcriptional reactivation. We identified distinct signatures that marked cells destined for positive selection versus apoptotic deletion. Differences in the expression of unexpectedly few genes accompanied commitment to the CD4(+) or CD8(+) lineage, a similarity that carried through to peripheral T cells and their activation, demonstrated by mass cytometry phosphoproteomics. The transcripts newly identified as encoding candidate mediators of key transitions help define the 'known unknowns' of thymocyte differentiation.

Identification of transcriptional regulators in the mouse immune system.

The differentiation of hematopoietic stem cells into cells of the immune system has been studied extensively in mammals, but the transcriptional circuitry that controls it is still only partially understood. Here, the Immunological Genome Project gene-expression profiles across mouse immune lineages allowed us to systematically analyze these circuits. To analyze this data set we developed Ontogenet, an algorithm for reconstructing lineage-specific regulation from gene-expression profiles across lineages. Using Ontogenet, we found differentiation stage-specific regulators of mouse hematopoiesis and identified many known hematopoietic regulators and 175 previously unknown candidate regulators, as well as their target genes and the cell types in which they act. Among the previously unknown regulators, we emphasize the role of ETV5 in the differentiation of γδ T cells. As the transcriptional programs of human and mouse cells are highly conserved, it is likely that many lessons learned from the mouse model apply to humans.

Sequestration of gut pathobionts in intraluminal casts, a mechanism to avoid dysregulated T cell activation by pathobionts.

T cells that express the transcription factor RORγ, regulatory (Treg), or conventional (Th17) are strongly influenced by intestinal symbionts. In a genetic approach to identify mechanisms underlying this influence, we performed a screen for microbial genes implicated, in germfree mice monocolonized with Escherichia coli Nissle. The loss of capsule-synthesis genes impaired clonal expansion and differentiation of intestinal RORγ+ T cells. Mechanistic exploration revealed that the capsule-less mutants remained able to induce species-specific immunoglobulin A (IgA) and were highly IgA-coated. They could still trigger myeloid cells, and more effectively damaged epithelial cells in vitro. Unlike wild-type microbes, capsule-less mutants were mostly engulfed in intraluminal casts, large agglomerates composed of myeloid cells extravasated into the gut lumen. We speculate that sequestration in luminal casts of potentially harmful microbes, favored by IgA binding, reduces the immune system's actual exposure, preserving host-microbe equilibrium. The variable immunostimulation by microbes that has been charted in recent years may not solely be conditioned by triggering molecules or metabolites but also by physical limits to immune system exposure.

Elevated Vitamin B12, Risk of Cancer, and Mortality: A Systematic Review.

Vitamin B12 (B12) is a molecule involved in several biological. Abnormally high levels are frequently found, but their causes can be multiple, and consequences have not been clearly elucidated. The objective of this review was to summarize the current evidence on the associations of elevated B12 and the development of cancer, and all-cause mortality in adults. Six references looking at mortality and seven looking at cancer risk were included. The evidence suggests an association between elevated B12 with a higher risk of cancer, with risk ratios ranging 1,88 to 5,9. There was less consistent evidence linking vitamin B12 and mortality.

Elevated B12 levels exceeding 1000 pg/L, if sustained and unexplainable, warrant a comprehensive individual assessment of each patient. This evaluation should encompass various potential factors contributing to the elevation, aiming to effectively guide the diagnostic process of neoplastic diseases.Clinical longitudinal observational studies have suggested a potential link between heightened B12 levels and the risks of cancer and mortality. Nonetheless, these studies have been retrospective cohort studies, and lack a defined threshold point of B12 levels.Studies have documented a positive correlation between elevated levels of B12 and the incidence of lung, pancreatic, and liver cancers, as well as certain hematological neoplasms, particularly those related to the myeloid lineage. Conversely, a consistent negative association has been observed in the context of breast cancer. Findings concerning neoplasms of the lower gastrointestinal tract and prostate display contradictory outcomes.The diagnostic significance of elevated B12 levels among patients already diagnosed with cancer remains uncertain and could potentially be linked to reverse causality.

Surveillance for Acute Flaccid Myelitis - United States, 2018-2022.

Acute flaccid myelitis (AFM) is a serious neurologic condition primarily affecting children; AFM can cause acute respiratory failure and permanent paralysis. AFM is a rare but known complication of various viral infections, particularly those of enteroviruses (EVs). Increases in AFM cases during 2014, 2016, and 2018 were associated with EV-D68 infection. This report examines trends in confirmed AFM cases during 2018-2022 and patients' clinical and laboratory characteristics. The number of AFM cases was low during 2019-2022 (28-47 cases per year); the number of cases remained low in 2022 despite evidence of increased EV-D68 circulation in the United States. Compared with cases during the most recent peak year (2018), fewer cases during 2019-2021 had upper limb involvement, prodromal respiratory or febrile illness, or cerebrospinal fluid pleocytosis, and more were associated with lower limb involvement. It is unclear why EV-D68 circulation in 2022 was not associated with an increase in AFM cases or when the next increase in AFM cases will occur. Nonetheless, clinicians should continue to suspect AFM in any child with acute flaccid limb weakness, especially those with a recent respiratory or febrile illness.

Total and segmental phase angle in a cohort of hospitalised patients with COVID-19: mortality prediction and changes throughout hospitalisation.

Body composition and phase angle (PhA) have been used to predict mortality in multiple diseases. However, little has been studied regarding segmental measurements, which could potentially help assess subtle changes in specific tissue segments. This study aimed to identify the total PhA cut-off point associated with mortality risk and changes in body composition within a week of hospitalisation in non-critical hospitalised patients with COVID-19. A cohort study was conducted where patients underwent to a complete nutritional assessment upon admission and after seven days, and followed up until hospital discharge or death. A receiver operating characteristic curve was constructed to determine the PhA cut-off point, and the Kaplan­Meier estimator was used to determine survival analysis. Segmental and complete body compositions on admission and after 7 d were compared. We included 110 patients (60 men) with a mean age of 50·5 ± 15·0 years and a median BMI of 28·5 (IQR, 25·6­33·5) kg/m2. The median length of hospital stay was 6 (IQR, 4­9) d, and the mortality rate was 13·6 %. The PhA cut-off point obtained was 4°, with significant differences in the survival rate (P < 0·001) and mortality (HR = 5·81, 95 % CI: 1·80, 18·67, P = 0·003). Segmental and whole-body compositions were negatively affected within one week of hospitalisation, with changes in the approach by the graphical method in both sexes. Nutritional status deteriorates within a week of hospitalisation. PhA < 4° is strongly associated with increased mortality in non-critical hospitalised patients with COVID-19.

Characterizing Gender and Leadership Trends Among Mohs Micrographic Surgery Fellowship Directors.

BACKGROUND: Fellowship directors (FDs) play a key role in shaping Mohs micrographic surgery (MMS). Studies characterizing director trends are lacking and may provide a framework for improving gender diversity. OBJECTIVE: To explore characteristics of FDs and trends in gender of both fellows and FDs over time. MATERIALS AND METHODS: The authors compiled a comprehensive list of FDs and fellows for all Accreditation Council for Graduate Medical Education-accredited Micrographic Surgery & Dermatologic Oncology programs from 1996 to 2023. Publicly available data from various internet sources from February 1, 2023 to May 30, 2023 were used to assess characteristics of MMS FDs. RESULTS: The percentage of female FDs increased from 6% to 25% from 1996 to 2023. Female directors were more likely to select female fellows than male directors ( p = .0002) and had fewer years between fellowship completion and FD appointment (9.1 ± 4.7 years) compared with male directors (13.6 ± 8.8 years; p = .036). H-index, program type, and academic rank were similar between male and female directors. CONCLUSION: Although gender parity among MMS trainees has been achieved, discrepancies remain in the gender composition of FDs. Further studies are required to determine why women are underrepresented as FDs.

Intravenous Vitamin C as an Add-on Therapy for the Treatment of Sepsis in an Intensive Care Unit: A Prospective Cohort Study.

Background and Objectives: According to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), sepsis is defined as "life-threatening organ dysfunction caused by a dysregulated host response to infection". The increased presence of free radicals causes an increase in oxidative stress. Vitamin C is an essential water-soluble vitamin with antioxidant activity and immunoregulatory effects that plays a potential role in the treatment of bacterial infections. Our aim was to evaluate the effectiveness of adding vitamin C to the conventional treatment of sepsis to decrease its mortality rate. Materials and Methods: In a prospective cohort study, we included patients with a diagnosis of sepsis and a SOFA score ≥ 9 who were evaluated in an Intensive Care Unit at a secondary-care hospital. According to the intensive care specialist, they were treated using two different strategies: Group 1-patients with sepsis treated with conventional treatment without vitamin C; Group 2-patients with sepsis with the addition of vitamin C to conventional treatment. Results: We included 34 patients with sepsis. The incidence of mortality was 38%, and 47% of patients used vitamin C as an adjuvant to the basic treatment of sepsis. In the basal analyses, patients treated with use of vitamin C compared to patients treated without vitamin C required less use of glucocorticoids (75% vs. 100%, p = 0.039). At follow-up, patients treated without vitamin C had higher mortality than patients treated with vitamin C as an adjuvant for the treatment of sepsis (55.6% vs. 18.8%, p = 0.03). We observed that the use of vitamin C was a protective factor for mortality in patients with sepsis (RR: 0.54, 95% CI: 0.31-0.96, p = 0.03). Conclusions: The use of vitamin C as an adjuvant to treatment decreases the risk of mortality by 46% in patients with sepsis and SOFA ≥ 9 compared to patients treated without vitamin C as an adjuvant to sepsis.

Constitutive High Expression of NOXA Sensitizes Human Embryonic Stem Cells for Rapid Cell Death.

Human embryonic stem (hES) cells are highly sensitive to apoptotic stimuli such as DNA damage, which allows for the rapid elimination of mutated cells during development. However, the mechanisms that maintain hES cells in the primed apoptotic state are not completely known. Key activators of apoptosis, the BH3-only proteins, are present at low levels in most cell types. In contrast, hES cells have constitutive high levels of the BH3-only protein, NOXA. We examined the importance of NOXA for enabling apoptosis in hES cells. hES cells deleted for NOXA showed remarkable protection against multiple apoptotic stimuli. NOXA was constitutively localized to the mitochondria, where it interacted with MCL1. Strikingly, inhibition of MCL1 in NOXA knockout cells was sufficient to sensitize these cells to DNA damage-induced cell death. Our study demonstrates that an essential function of constitutive high levels of NOXA in hES cells is to effectively antagonize MCL1 to permit rapid apoptosis.

Prevalence of adiposity-based chronic disease and its association with anthropometric and clinical indices: a cross-sectional study.

The present study aimed to determine the prevalence of adiposity-based chronic disease (ABCD) and its association with anthropometric indices in the Mexican population. A cross-sectional study was conducted in 514 adults seen at a clinical research unit. The American Association of Clinical Endocrinology/AACE/ACE criteria were used to diagnose ABCD by first identifying subjects with BMI ≥ 25 kg/m2 and those with BMI of 23-24·9 kg/m2 and waist circumference ≥ 80 cm in women or ≥ 90 cm in men. The presence of metabolic and clinical complications associated with adiposity, such as factors related to metabolic syndrome, prediabetes, type 2 diabetes, dyslipidaemia and arterial hypertension, were subsequently evaluated. Anthropometric indices related to cardiometabolic risk factors were then determined. The results showed the prevalence of ABCD was 87·4 % in total, 91·5 % in men and 86 % in women. The prevalence of ABCD stage 0 was 2·4 %, stage 1 was 33·7 % and stage 2 was 51·3 %. The prevalence of obesity according to BMI was 57·6 %. The waist/hip circumference index (prevalence ratio (PR) = 7·57; 95 % CI 1·52, 37·5) and the conicity index (PR = 3·46; 95 % CI 1·34, 8·93) were better predictors of ABCD, while appendicular skeletal mass % and skeletal muscle mass % decreased the risk of developing ABCD (PR = 0·93; 95 % CI 0·90, 0·96; and PR = 0·95; 95 % CI 0·93, 0·98). In conclusion, the prevalence of ABCD in our study was 87·4 %. This prevalence increased with age. It is important to emphasise that one out of two subjects had severe obesity-related complications (ABCD stage 2).

Simulation and Economic Analysis of the Biotechnological Potential of Biomass Production from a Microalgal Consortium.

The biomass of microalgae and the compounds that can be obtained from their processing are of great interest for various economic sectors. Chlorophyll from green microalgae has biotechnological applications of great potential in different industrial areas such as food, animal feed, pharmaceuticals, cosmetics, and agriculture. In this paper, the experimental, technical and economic performance of biomass production from a microalgal consortium (Scenedesmus sp., Chlorella sp., Schroderia sp., Spirulina sp., Pediastrum sp., and Chlamydomonas sp.) was investigated in three cultivation systems (phototrophic, heterotrophic and mixotrophic) in combination with the extraction of chlorophyll (a and b) on a large scale using simulation; 1 ha was established as the area for cultivation. In the laboratory-scale experimental stage, biomass and chlorophyll concentrations were determined for 12 days. In the simulation stage, two retention times in the photobioreactor were considered, which generated six case studies for the culture stage. Subsequently, a simulation proposal for the chlorophyll extraction process was evaluated. The highest microalgae biomass concentration was 2.06 g/L in heterotrophic culture, followed by mixotrophic (1.98 g/L). Phototrophic and mixotrophic cultures showed the highest chlorophyll concentrations of 20.5 µg/mL and 13.5 µg/mL, respectively. The simulation shows that higher biomass and chlorophyll production is attained when using the mixotrophic culture with 72 h of retention that we considered to evaluate chlorophyll production (a and b). The operating cost of the entire process is very high; the cultivation stage has the highest operating cost (78%), mainly due to the high energy consumption of the photobioreactors.

Changing Epidemiology of Varicella Outbreaks in the United States During the Varicella Vaccination Program, 1995-2019.

We describe the changing epidemiology of varicella outbreaks informed by past and current active and passive surveillance in the United States by reviewing data published during 1995-2015 and analyzing new data from 2016 to 2019. Varicella outbreaks were defined as ≥5 varicella cases within 1 setting and ≥1 incubation period. During the 1-dose varicella vaccination program (1995‒2006), the number of varicella outbreaks declined by 80% (2003-2006 vs 1995-1998) in 1 active surveillance area where vaccination coverage reached 90.5% in 2006. During the 2-dose program, in 7 states with consistent reporting to the Centers for Disease Control and Prevention, the number of outbreaks declined by 82% (2016-2019 vs 2005-2006). Over the entire program (1995-2019), outbreak size and duration declined from a median of 15 cases/outbreak and 45 days duration to 7 cases and 30 days duration. The proportion of outbreaks with <10 cases increased from 28% to 73%. During 2016‒2019, most (79%) outbreak cases occurred among unvaccinated or partially vaccinated persons eligible for second-dose vaccination, highlighting the potential for further varicella control.

Monitoring Varicella Vaccine Impact on Varicella Incidence in the United States: Surveillance Challenges and Changing Epidemiology, 1995-2019.

Surveillance is critical for monitoring vaccine impact. Varicella surveillance challenges predated varicella vaccine US licensure in 1995. Several interim steps were needed before case-based surveillance could be established in most states, and both active and passive surveillance was needed to document the vaccination program's impact on varicella incidence. By the end of the 1-dose program in 2005, incidence had declined 90% in the active surveillance areas, with significant declines occurring in all age groups within 5 years of program implementation. Additional declines occurred during the 2-dose program leading to >97% decline in incidence over the 25 years of program implementation through 2019, based on data from 4 states with continuous passive reporting. Surveillance showed that declines were highest among children and adolescents covered by the routine vaccination recommendations but occurred in all age groups. Although surveillance systems changed and were adapted to reflect evolving epidemiology, data consistently demonstrated decreasing varicella incidence following the vaccination program implementation. The vaccination program dramatically decreased virus circulation and increased community protection. Continued and improved varicella surveillance is needed to accurately monitor disease epidemiology and further guide prevention efforts.

Decline in Severe Varicella Disease During the United States Varicella Vaccination Program: Hospitalizations and Deaths, 1990-2019.

To describe the impact of the US varicella vaccination program on severe varicella outcomes, we analyzed varicella hospitalizations using the National Inpatient Sample 1993-2019 and varicella deaths using the National Center for Health Statistics data 1990-2019. Over 25 years of vaccination program (1995-2019), varicella hospitalizations, and deaths declined 94% and 97%, respectively, among persons aged <50 years. Most of the decline (∼90%) occurred during the 1-dose period (through 2006/2007) by attaining and maintaining high vaccination coverage; additional declines occurred during the 2-dose period, especially in the age groups covered by the 2-dose recommendation. The greatest decline for both hospitalizations and deaths (97% and >99%, respectively) was among persons aged <20 years, born during the varicella vaccination program. In the <20 age group, varicella hospitalization has become a rare event, and varicella deaths have been practically eliminated in the United States. A total of >10 500 varicella hospitalizations and 100 varicella deaths are now prevented annually in the United States as a direct result of vaccination and reduction in varicella-zoster virus circulation.

Increase in Acute Respiratory Illnesses Among Children and Adolescents Associated with Rhinoviruses and Enteroviruses, Including Enterovirus D68 - United States, July-September 2022.

Increases in severe respiratory illness and acute flaccid myelitis (AFM) among children and adolescents resulting from enterovirus D68 (EV-D68) infections occurred biennially in the United States during 2014, 2016, and 2018, primarily in late summer and fall. Although EV-D68 annual trends are not fully understood, EV-D68 levels were lower than expected in 2020, potentially because of implementation of COVID-19 mitigation measures (e.g., wearing face masks, enhanced hand hygiene, and physical distancing) (1). In August 2022, clinicians in several geographic areas notified CDC of an increase in hospitalizations of pediatric patients with severe respiratory illness and positive rhinovirus/enterovirus (RV/EV) test results.* Surveillance data were analyzed from multiple national data sources to characterize reported trends in acute respiratory illness (ARI), asthma/reactive airway disease (RAD) exacerbations, and the percentage of positive RV/EV and EV-D68 test results during 2022 compared with previous years. These data demonstrated an increase in emergency department (ED) visits by children and adolescents with ARI and asthma/RAD in late summer 2022. The percentage of positive RV/EV test results in national laboratory-based surveillance and the percentage of positive EV-D68 test results in pediatric sentinel surveillance also increased during this time. Previous increases in EV-D68 respiratory illness have led to substantial resource demands in some hospitals and have also coincided with increases in cases of AFM (2), a rare but serious neurologic disease affecting the spinal cord. Therefore, clinicians should consider AFM in patients with acute flaccid limb weakness, especially after respiratory illness or fever, and ensure prompt hospitalization and referral to specialty care for such cases. Clinicians should also test for poliovirus infection in patients suspected of having AFM because of the clinical similarity to acute flaccid paralysis caused by poliovirus. Ongoing surveillance for EV-D68 is critical to ensuring preparedness for possible future increases in ARI and AFM.

Public Health Response to a Case of Paralytic Poliomyelitis in an Unvaccinated Person and Detection of Poliovirus in Wastewater - New York, June-August 2022.

On July 18, 2022, the New York State Department of Health (NYSDOH) notified CDC of detection of poliovirus type 2 in stool specimens from an unvaccinated immunocompetent young adult from Rockland County, New York, who was experiencing acute flaccid weakness. The patient initially experienced fever, neck stiffness, gastrointestinal symptoms, and limb weakness. The patient was hospitalized with possible acute flaccid myelitis (AFM). Vaccine-derived poliovirus type 2 (VDPV2) was detected in stool specimens obtained on days 11 and 12 after initial symptom onset. To date, related Sabin-like type 2 polioviruses have been detected in wastewater* in the patient's county of residence and in neighboring Orange County up to 25 days before (from samples originally collected for SARS-CoV-2 wastewater monitoring) and 41 days after the patient's symptom onset. The last U.S. case of polio caused by wild poliovirus occurred in 1979, and the World Health Organization Region of the Americas was declared polio-free in 1994. This report describes the second identification of community transmission of poliovirus in the United States since 1979; the previous instance, in 2005, was a type 1 VDPV (1). The occurrence of this case, combined with the identification of poliovirus in wastewater in neighboring Orange County, underscores the importance of maintaining high vaccination coverage to prevent paralytic polio in persons of all ages.

Wastewater Testing and Detection of Poliovirus Type 2 Genetically Linked to Virus Isolated from a Paralytic Polio Case - New York, March 9-October 11, 2022.

In July 2022, a case of paralytic poliomyelitis resulting from infection with vaccine-derived poliovirus (VDPV) type 2 (VDPV2)§ was confirmed in an unvaccinated adult resident of Rockland County, New York (1). As of August 10, 2022, poliovirus type 2 (PV2)¶ genetically linked to this VDPV2 had been detected in wastewater** in Rockland County and neighboring Orange County (1). This report describes the results of additional poliovirus testing of wastewater samples collected during March 9-October 11, 2022, and tested as of October 20, 2022, from 48 sewersheds (the community area served by a wastewater collection system) serving parts of Rockland County and 12 surrounding counties. Among 1,076 wastewater samples collected, 89 (8.3%) from 10 sewersheds tested positive for PV2. As part of a broad epidemiologic investigation, wastewater testing can provide information about where poliovirus might be circulating in a community in which a paralytic case has been identified; however, the most important public health actions for preventing paralytic poliomyelitis in the United States remain ongoing case detection through national acute flaccid myelitis (AFM) surveillance†† and improving vaccination coverage in undervaccinated communities. Although most persons in the United States are sufficiently immunized, unvaccinated or undervaccinated persons living or working in Kings, Orange, Queens, Rockland, or Sullivan counties, New York should complete the polio vaccination series as soon as possible.

Effect of the BCAT2 polymorphism (rs11548193) on plasma branched-chain amino acid concentrations after dietary intervention in subjects with obesity and insulin resistance.

Branched-chain amino acids (BCAA) are considered markers of insulin resistance (IR) in subjects with obesity. In this study, we evaluated whether the presence of the SNP of the branched-chain aminotransferase 2 (BCAT2) gene can modify the effect of a dietary intervention (DI) on the plasma concentration of BCAA in subjects with obesity and IR. A prospective cohort study of adult subjects with obesity, BMI ≥ 30 kg/m2, homeostatic model assessment-insulin resistance (HOMA-IR ≥ 2·5) no diagnosed chronic disease, underwent a DI with an energy restriction of 3140 kJ/d and nutritional education for 1 month. Anthropometric measurements, body composition, blood pressure, resting energy expenditure, oral glucose tolerance test results, serum biochemical parameters and the plasma amino acid profile were evaluated before and after the DI. SNP were assessed by the TaqMan SNP genotyping assay. A total of eighty-two subjects were included, and fifteen subjects with a BCAT2 SNP had a greater reduction in leucine, isoleucine, valine and the sum of BCAA. Those subjects also had a greater reduction in skeletal muscle mass, fat-free mass, total body water, blood pressure, muscle strength and biochemical parameters after 1 month of the DI and adjusting for age and sex. This study demonstrated that the presence of the BCAT2 SNP promotes a greater reduction in plasma BCAA concentration after adjusting for age and sex, in subjects with obesity and IR after a 1-month energy-restricted DI.