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Non-nutritive sweeteners (NNSs) provide a sweet taste to foods and beverages without significantly adding calories. Still, their consumption has been linked to modifications in adult's and children's gut microbiota and the disruption of blood glucose control. Human milk microbiota are paramount in establishing infants' gut microbiota, but very little is known about whether the consumption of sweeteners can alter it. To address this question, we sequenced DNA extracted colostrum samples from a group of mothers, who had different levels of NNS consumption, using the Ion Torrent Platform. Our results show that the "core" of colostrum microbiota, composed of the genera Bifidobacterium, Blautia, Cutibacteium, Staphylococcus, and Streptococcus, remains practically unchanged with the consumption of NNS during pregnancy, but specific genera display significant alterations, such as Staphylococcus and Streptococcus. A significant increase in the unclassified archaea Methanobrevibacter spp. was observed as the consumption frequency of NNS increased. The increase in the abundance of this archaea has been previously linked to obesity in Mexican children. NNS consumption during pregnancy could be related to changes in colostrum microbiota and may affect infants' gut microbiota seeding and their future health.
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Microbiota , Adoçantes não Calóricos , Gravidez , Feminino , Adulto , Criança , Humanos , Colostro , Edulcorantes , Ingestão de EnergiaRESUMO
Breast cancer (BC) is the most frequent malignant neoplasia and leading cause of cancer mortality for women. A timely diagnosis of BC is crucial to ensure the best chances of survival. Among the various screening tools for BC, antibodies directed towards self-antigens or tumor-associated antigens (autoantibodies) have emerged as an alternative to image-based screening modalities. However, little attention has been paid to the global diversity of autoantibodies. This work aimed to analyze the diversity of autoantibodies reactive to antigens expressed by the BC cell line T47D in the sera of Mexican women with BC, benign breast pathology (BBP), or without breast pathology (WBP). We found that the diversity of antibodies in the sera was higher in the BC and BBP groups than in the WBP group. Likewise, the diversity changed with the progression of BC. Our results show and measure the complexity of the antibody response in breast health and disease.
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Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/patologia , Autoanticorpos , Antígenos de NeoplasiasRESUMO
Robust data in animals show that sucralose intake during gestation can predispose the offspring to weight gain, metabolic disturbances, and low-grade systemic inflammation; however, concluding information remains elusive in humans. In this cross-sectional, prospective study, we examined the birth weight, glucose and insulin cord blood levels, monocyte subsets, and inflammatory cytokine profile in 292 neonates at term from mothers with light sucralose ingestion (LSI) of less than 60 mg sucralose/week or heavy sucralose intake (HSI) of more than 36 mg sucralose/day during pregnancy. Mothers in the LSI (n = 205) or HSI (n = 87) groups showed no differences in age, pregestational body mass index, blood pressure, and glucose tolerance. Although there were no differences in glucose, infants from HSI mothers displayed significant increases in birth weight and insulin compared to newborns from LSI mothers. Newborns from HSI mothers showed a substantial increase in the percentage of inflammatory nonclassical monocytes compared to neonates from LSI mothers. Umbilical cord tissue of infants from HSI mothers exhibited higher IL-1 beta and TNF-alpha with lower IL-10 expression than that found in newborns from LSI mothers. Present results demonstrate that heavy sucralose ingestion during pregnancy affects neonates' anthropometric, metabolic, and inflammatory features.
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Background: A diet containing non-caloric sweeteners (NCS) could reduce calorie intake; conversely, some animal studies suggest that NCS consumption may increase functional gastrointestinal disorder symptoms (FGDs). This study aimed to compare the effect of consuming a diet containing NCS (c-NCS) versus a non-caloric sweetener-free diet (NCS-f) on FGDs. Methods: We conducted a randomized, controlled, parallel-group study using two different diets for five weeks: the c-NCS diet contained 50−100 mg/day NCS, whereas the NCS-f diet had less than 10 mg/day NCS. At the beginning of the study (PreTx) and at the end (PostTx), we assessed FGDs, dietary intake, and NCS consumption. Results: The percentage of participants with diarrhea (PreTx = 19% vs. PstTx = 56%; p = 0.02), post-prandial discomfort (PreTx = 9% vs. PstTx = 39%; p = 0.02), constipation (PreTx = 30% vs. PostTx = 56%; p < 0.01), and burning (PreTx = 13% vs. PostTx = 33%; p < 0.01) increased in the c-NCS diet group. Conversely, abdominal pain (PreTx = 15% vs. PostTx = 3%; p = 0.04), post-prandial discomfort (PreTx = 26% vs. PostTx = 6%; p = 0.02), burning (PreTx = 15% vs. PostTx = 0%; p = 0.02), early satiety (PreTx = 18% vs. PostTx = 3%; p < 0.01), and epigastric pain (PreTx = 38% vs. PostTx = 3%; p < 0.01) decreased in the NCS-f diet group. Conclusion: A c-NCS diet is associated with increased FGDs, including diarrhea, post-prandial discomfort, constipation, and burning or retrosternal pain. The NCS-f diet also decreased FGDs, as well as abdominal pain, post-prandial discomfort, burning or retrosternal pain, early satiety, and epigastric pain.
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Gastroenteropatias , Edulcorantes , Dor Abdominal/etiologia , Animais , Dieta , Ingestão de EnergiaRESUMO
Sucralose consumption alters microbiome and carbohydrate metabolism in mouse models. However, there are no conclusive studies in humans. Our goals were to examine the effect of sucralose consumption on the intestinal abundance of bacterial species belonging to Actinobacteria, Bacteroidetes, and Firmicutes and explore potential associations between microbiome profiles and glucose and insulin blood levels in healthy young adults. In this open-label clinical trial, volunteers randomly drank water, as a control (n = 20), or 48 mg sucralose (n = 20), every day for ten weeks. At the beginning and the end of the study, participants were subjected to an oral glucose tolerance test (OGTT) to measure serum glucose and insulin every 15 min for 3 h and provided fecal samples to assess gut microbiota using a quantitative polymerase chain reaction. Sucralose intake altered the abundance of Firmicutes without affecting Actinobacteria or Bacteroidetes. Two-way ANOVA revealed that volunteers drinking sucralose for ten weeks showed a 3-fold increase in Blautia coccoides and a 0.66-fold decrease in Lactobacillus acidophilus compared to the controls. Sucralose consumption increased serum insulin and the area under the glucose curve compared to water. Long-term sucralose ingestion induces gut dysbiosis associated with altered insulin and glucose levels during an OGTT.
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Increasing evidence has demonstrated that oxidized low-density lipoproteins (oxLDL) and lipopolysaccharide (LPS) enhance accumulation of interleukin (IL)-1 beta-producing macrophages in atherosclerotic lesions. However, the potential synergistic effect of native LDL (nLDL) and LPS on the inflammatory ability and migration pattern of monocyte subpopulations remains elusive and is examined here. In vitro, whole blood cells from healthy donors (n = 20) were incubated with 100 µg/mL nLDL, 10 ng/mL LPS, or nLDL + LPS for 9 h. Flow cytometry assays revealed that nLDL significantly decreases the classical monocyte (CM) percentage and increases the non-classical monocyte (NCM) subset. While nLDL + LPS significantly increased the number of NCMs expressing IL-1 beta and the C-C chemokine receptor type 2 (CCR2), the amount of NCMs expressing the CX3C chemokine receptor 1 (CX3CR1) decreased. In vivo, patients (n = 85) with serum LDL-cholesterol (LDL-C) >100 mg/dL showed an increase in NCM, IL-1 beta, LPS-binding protein (LBP), and Castelli's atherogenic risk index as compared to controls (n = 65) with optimal LDL-C concentrations (≤100 mg/dL). This work demonstrates for the first time that nLDL acts in synergy with LPS to alter the balance of human monocyte subsets and their ability to produce inflammatory cytokines and chemokine receptors with prominent roles in atherogenesis.
Assuntos
Receptor 1 de Quimiocina CX3C/genética , LDL-Colesterol/farmacologia , Interleucina-1beta/genética , Lipopolissacarídeos/farmacologia , Monócitos/efeitos dos fármacos , Receptores CCR2/genética , Proteínas de Fase Aguda/genética , Proteínas de Fase Aguda/imunologia , Adolescente , Adulto , Proteína C-Reativa/genética , Proteína C-Reativa/imunologia , Receptor 1 de Quimiocina CX3C/imunologia , Proteínas de Transporte/genética , Proteínas de Transporte/imunologia , Linhagem da Célula/efeitos dos fármacos , Linhagem da Célula/imunologia , HDL-Colesterol/sangue , Sinergismo Farmacológico , Feminino , Citometria de Fluxo , Expressão Gênica , Voluntários Saudáveis , Humanos , Interleucina-1beta/imunologia , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/imunologia , Pessoa de Meia-Idade , Monócitos/citologia , Monócitos/imunologia , Cultura Primária de Células , Receptores CCR2/imunologia , Triglicerídeos/sangueRESUMO
PURPOSE: To evaluate the combination of fundus autofluorescence results with several clinical and structural variables into mathematical indexes to enhance their ability to predict visual and anatomical changes after the antivascular endothelial growth factor loading dose. METHODS: Patients with diabetic macular edema were enrolled. Each patient had a comprehensive ophthalmological examination, contrast sensitivity, optical coherence tomography, and fundus autofluorescence assessment. All patients received three monthly doses of ziv-aflibercept and were followed each month for response assessment. Autofluorescence was classified according to its level into five grades. The grades were combined with other variables (best-corrected visual acuity, contrast sensitivity, central macular thickness, macular cube volume, and macular cube average thickness) into normalized indexes. Statistical assessment was done using a Spearman's rank correlation coefficient, linear regression, and interobserver-agreement analysis. RESULTS: There was a strong correlation between the fundus autofluorescence/baseline best-corrected visual acuity index and the fundus autofluorescence/contrast-sensitivity index at baseline with the best-corrected visual acuity after the third dose of ziv-aflibercept (rs = -0.78, p = .000 and rs = -0.68, p = .0009 respectively). The fundus autofluorescence/baseline best-corrected visual acuity index and the fundus autofluorescence/contrast-sensitivity index, both at baseline had a mild correlation with the macular volume at 1 month of follow-up (rs = 0.56, p = .008 and (rs = 0.64, p = .002, respectively). CONCLUSION: This study suggests that it is possible to combine fundus autofluorescence results with functional and structural variables into normalized indexes that could potentially predict outcomes after antivascular endothelial growth factor loading dose in patients with diabetic macular edema.
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How T cells integrate environmental cues into signals that limit the magnitude and length of immune responses is poorly understood. Here, we provide data that demonstrate that B55ß, a regulatory subunit of protein phosphatase 2A, represents a molecular link between cytokine concentration and apoptosis in activated CD8+ T cells. Through the modulation of AKT, B55ß induced the expression of the proapoptotic molecule Hrk in response to cytokine withdrawal. Accordingly, B55ß and Hrk were both required for in vivo and in vitro contraction of activated CD8+ lymphocytes. We show that this process plays a role during clonal contraction, establishment of immune memory, and preservation of peripheral tolerance. This regulatory pathway may represent an unexplored opportunity to end unwanted immune responses or to promote immune memory.
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Linfócitos T CD8-Positivos/imunologia , Memória Imunológica , Proteína Fosfatase 2/imunologia , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/imunologia , Camundongos , Camundongos Transgênicos , Neuropeptídeos/genética , Neuropeptídeos/imunologia , Proteína Fosfatase 2/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/imunologiaRESUMO
BACKGROUND: Non-nutritive sweeteners (NNS) are widely consumed by humans due to their apparent innocuity, especially sucralose. However, several studies link sucralose consumption to weight gain and metabolic derangements, although data are still contradictory. OBJECTIVE: To determine the effect of acute and chronic consumption of sucralose on insulin and glucose profiles in young healthy adults. MATERIAL AND METHODS: This was a randomized, parallel, double-blind, placebo-controlled trial conducted in healthy young adults from 18 to 35 years old, without insulin resistance. A hundred thirty seven participants were randomized into three groups: a) volunteers receiving 48 mg sucralose, b) volunteers receiving 96 mg sucralose, and c) controls receiving water as placebo. All participants underwent a 3-h oral glucose tolerance test (OGTT) preceded by consuming sucralose or placebo 15 min before glucose load, at two time points: week zero (Wk0) and week ten (Wk10). Serum insulin and glucose were measured every 15 min during both OGTTs. RESULTS: Compared to Wk0, consumption of sucralose for 10 weeks provoked 1) increased insulin concentrations at 0 min (7.5 ± 3.4 vs 8.8 ± 4.1 µIU/mL; p = 0.01), 30 min (91.3 ± 56.2 vs 110.1 ± 49.4 µIU/mL; p = 0.05), 105 min (47.7 ± 24.4 vs 64.3 ± 48.2 µIU/mL; p = 0.04) and 120 min (44.8 ± 22.1 vs 63.1 ± 47.8 µIU/mL; p = 0.01) in the 48 mg sucralose group; 2) increased blood glucose at - 15 min (87.9 ± 4.6 vs 91.4 ± 5.4 mg/dL; p = 0.003), 0 min (88.7 ± 4 vs 91.3 ± 6 mg/dL; p = 0.04) and 120 min (95.2 ± 23.7 vs 106.9 ± 19.5 mg/dL; p = 0.009) in the 48 mg sucralose group; 3) increased area under the curve (AUC) of insulin in both 48 and 96 mg sucralose groups (9262 vs 11,398; p = 0.02 and 6962 vs 8394; p = 0.12, respectively); and 4) reduced Matsuda index in the 48 mg sucralose group (6.04 ± 3.19 vs 4.86 ± 2.13; p = 0.01). CONCLUSIONS: These data show that chronic consumption of sucralose can affect insulin and glucose responses in non-insulin resistant healthy young adults with normal body mass index (between 18.5 and 24.9 kg/m2), however, the effects are not consistent with dose; further research is required. CLINICAL TRIAL REGISTRY: NCT03703141.
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Insulina/sangue , Sacarose/análogos & derivados , Edulcorantes/farmacologia , Adolescente , Adulto , Glicemia/efeitos dos fármacos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Sacarose/administração & dosagem , Sacarose/farmacologia , Tempo , Adulto JovemRESUMO
Sucralose is a noncaloric artificial sweetener that is widely consumed worldwide and has been associated with alteration in glucose and insulin homeostasis. Unbalance in monocyte subpopulations expressing CD11c and CD206 hallmarks metabolic dysfunction but has not yet been studied in response to sucralose. Our goal was to examine the effect of a single sucralose sip on serum insulin and blood glucose and the percentages of classical, intermediate, and nonclassical monocytes in healthy young adults subjected to an oral glucose tolerance test (OGTT). This study was a randomized, placebo-controlled clinical trial. Volunteers randomly received 60 mL water as placebo (n = 20) or 48 mg sucralose dissolved in 60 mL water (n = 25), fifteen minutes prior to an OGTT. Blood samples were individually drawn every 15 minutes for 180 minutes for quantifying glucose and insulin concentrations. Monocyte subsets expressing CD11c and CD206 were measured at -15 and 180 minutes by flow cytometry. As compared to controls, volunteers receiving sucralose exhibited significant increases in serum insulin at 30, 45, and 180 minutes, whereas blood glucose values showed no significant differences. Sucralose consumption caused a significant 7% increase in classical monocytes and 63% decrease in nonclassical monocytes with respect to placebo controls. Pearson's correlation models revealed a strong association of insulin with sucralose-induced monocyte subpopulation unbalance whereas glucose values did not show significant correlations. Sucralose ingestion decreased CD11c expression in all monocyte subsets and reduced CD206 expression in nonclassical monocytes suggesting that sucralose does not only unbalance monocyte subpopulations but also alter their expression pattern of cell surface molecules. This work demonstrates for the first time that a 48 mg sucralose sip increases serum insulin and unbalances monocyte subpopulations expressing CD11c and CD206 in noninsulin-resistant healthy young adults subjected to an OGTT. The apparently innocuous consumption of sucralose should be reexamined in light of these results.