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BACKGROUND: Nutrition transition and recent changes in lifestyle in Middle Eastern countries have resulted in the double burden of malnutrition. In Egypt, 88% of urban women are overweight or obese and 50% are iron deficient. Their energy, sugar, and sodium intakes are excessive, while intakes of iron, vitamin D, and folate are insufficient. OBJECTIVE: This study aimed to formulate dietary advice based on locally consumed and affordable foods and determine the need for fortified products to meet the nutrient requirements of urban Egyptian women. METHODS: Food intakes were assessed using a 4-d food diary collected from 130 urban Egyptian women aged 19-30 y. Food prices were collected from modern and traditional markets to calculate diet cost. Population-based linear and goal programming analyses (Optifood tool) were used to identify "limiting nutrients" and to assess whether locally consumed foods (i.e., consumed by >5% of women) could theoretically improve nutrient adequacy at an affordable cost (i.e., less than or equal to the mean diet cost), while meeting recommendations for SFAs, sugars, and sodium. The potential of hypothetical fortified foods for improving intakes of micronutrients was also assessed. RESULTS: Iron was the most limiting nutrient. Daily consumption of fruits, vegetables, milk or yogurt, meat/fish/eggs, and tahini (sesame paste) were likely to improve nutrient adequacy for 11 out of 12 micronutrients modeled. Among fortified foods tested, iron-fortified rice, milk, water, bread, or yogurt increased the minimized iron content of the modeled diet from 40% to >60% of the iron recommendation. CONCLUSIONS: A set of dietary advice based on locally consumed foods, if put into practice, can theoretically meet requirements for most nutrients, except for iron for which adequacy is harder to achieve without fortified products. The acceptability of the dietary changes modeled needs evaluation before promoting them to young Egyptian women.
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Dieta , Hierro , Necesidades Nutricionales , Adulto , Egipto , Femenino , Alimentos Fortificados , Humanos , Micronutrientes , Población Urbana , Adulto JovenRESUMEN
BACKGROUND: Basophil activation contributes to inflammatory reactions, especially in allergy. It is controlled, both positively and negatively, by several mechanisms. High-affinity IgE receptors (FcεRI) generate a mixture of activation and inhibition signals when aggregated, the ratio of which depends on the concentration of allergen recognized by receptor-bound IgE. Low-affinity IgG receptors (FcγRIIA/B) generate inhibition signals when coengaged with FcεRI by allergen-antibody immune complexes. Commensal and probiotic bacteria, such as Lactobacillus paracasei, generate inhibition signals through still unclear mechanisms. OBJECTIVE: We sought to investigate whether mechanisms that control, both positively and negatively, basophil activation, which were unraveled and studied in basophils from healthy donors, are functional in allergic patients. METHODS: FcεRI and FcγRIIA/B expression, FcεRI-dependent activation, FcεRI-dependent inhibition, and FcγRIIB-dependent inhibition were examined in blood basophils incubated overnight with or without L paracasei and challenged under 10 experimental conditions. Basophils from healthy donors were compared with basophils from patients who consulted an allergology outpatient clinic over a period of 3 months with respiratory allergy, anaphylaxis antecedents, chronic urticaria, and/or atopic dermatitis. RESULTS: Patients' basophils expressed neither more FcεRI nor less FcγRIIB than basophils from healthy donors. They were neither hyperreactive to positive regulation nor hyporeactive to negative regulation, irrespective of the receptors or mechanisms involved and the allergic manifestations of the patients. CONCLUSION: Regulatory mechanisms that control basophil activation are fully functional in allergic patients. Intrinsic defects in these mechanisms do not explain allergic manifestations. Based on these mechanisms, immune checkpoint modifiers can be developed as novel therapeutic tools for allergy.
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Basófilos/inmunología , Hipersensibilidad/inmunología , Adolescente , Adulto , Anciano , Femenino , Humanos , Lacticaseibacillus paracasei/inmunología , Masculino , Persona de Mediana Edad , Receptores de IgE/inmunología , Receptores de IgG/inmunología , Adulto JovenRESUMEN
BACKGROUND: The use of probiotics to improve anti-microbial defence, such as for influenza infections, is increasingly recommended. However, no data are available on the effect of probiotics on flu-associated secondary bacterial infections. There is strong evidence of a spatiotemporal association between influenza virus infection and invasive Neisseria meningitidis. We thus investigated the effect of feeding mice Lactobacillus paracasei CNCM I-1518 in a mouse model of sequential influenza-meningococcal infection. METHODS: We intranasally infected BALB/c mice with a strain of influenza A virus (IAV) H3N2 that was first adapted to mice. Seven days later, a secondary bacterial infection was induced by intranasal administration of bioluminescent N. meningitidis. During the experiment, mice orally received either L. paracasei CNCM I-1518 or PBS as a control. The effect of L. paracasei administration on secondary bacterial infection by N. meningitidis was evaluated. RESULTS: Oral consumption of L. paracasei CNCM I-1518 reduced the weight loss of infected mice and lowered the bioluminescent signal of infecting meningococci. This improvement was associated with higher recruitment of inflammatory myeloid cells, such as interstitial monocytes and dendritic cells, to the lungs. CONCLUSIONS: Our data highlight the role of the gut-lung axis. L. paracasei CNCM I-1518 may boost the defence against IAV infection and secondary bacterial infection, which should be further studied and validated in clinical trials.
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Lacticaseibacillus paracasei/fisiología , Infecciones Meningocócicas/prevención & control , Infecciones por Orthomyxoviridae/patología , Probióticos/uso terapéutico , Administración Oral , Animales , Coinfección/prevención & control , Citocinas/análisis , Modelos Animales de Enfermedad , Femenino , Subtipo H3N2 del Virus de la Influenza A/patogenicidad , Infecciones Meningocócicas/patología , Ratones , Ratones Endogámicos BALB C , Neisseria meningitidis/patogenicidad , Imagen ÓpticaRESUMEN
Iron fortification to prevent anemia in African infants increases colonic iron levels, favoring the growth of enteropathogens. The use of prebiotics may be an effective strategy to reduce these detrimental effects. Using the African infant PolyFermS gut model, we compared the effect of the prebiotics short-chain galacto- with long-chain fructo-oligosaccharides (scGOS/lcFOS) and native inulin, and the emerging prebiotic acacia gum, a branched-polysaccharide-protein complex consisting of arabinose and galactose, during iron supplementation on four Kenyan infant gut microbiota. Iron supplementation did not alter the microbiota but promoted Clostridioides difficile in one microbiota. The prebiotic effect of scGOS/lcFOS and inulin was confirmed during iron supplementation in all investigated Kenyan infant gut microbiota, leading to higher abundance of bifidobacteria, increased production of acetate, propionate, and butyrate, and a significant shift in microbiota composition compared to non-supplemented microbiota. The abundance of the pathogens Clostridium difficile and Clostridium perfringens was also inhibited upon addition of the prebiotic fibers. Acacia gum had no effect on any of the microbiota. In conclusion, scGOS/lcFOS and inulin, but not acacia gum, showed a donor-independent strong prebiotic potential in Kenyan infant gut microbiota. This study demonstrates the relevance of comparing fibers in vitro prior to clinical studies.
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BACKGROUND: Iron fortificants tend to be poorly absorbed and may adversely affect the gut, especially in African children. OBJECTIVE: We assessed the effects of prebiotic galacto-oligosaccharides/fructo-oligosaccharides (GOS/FOS) on iron absorption and gut health when added to iron-fortified infant cereal. METHODS: We randomly assigned Kenyan infants (n = 191) to receive daily for 3 wk a cereal containing iron and 7.5 g GOS/FOS (7.5 g+iron group), 3 g (3-g+iron group) GOS/FOS, or no prebiotics (iron group). A subset of infants in the 2 prebiotic+iron groups (n = 66) consumed 4 stable iron isotope-labeled test meals without and with prebiotics, both before and after the intervention. Primary outcome was fractional iron absorption (FIA) from the cereal with or without prebiotics regardless of dose, before and after 3 wk of consumption. Secondary outcomes included fecal gut microbiota, iron and inflammation status, and effects of prebiotic dose. RESULTS: Median (25th-75th percentiles) FIAs from meals before intervention were as follows: 16.3% (8.0%-27.6%) without prebiotics compared with 20.5% (10.4%-33.4%) with prebiotics (Cohen d = 0.53; P < 0.001). FIA from the meal consumed without prebiotics after intervention was 22.9% (8.5%-32.4%), 41% higher than from the meal without prebiotics before intervention (Cohen d = 0.36; P = 0.002). FIA from the meal consumed with prebiotics after intervention was 26.0% (12.2%-36.1%), 60% higher than from the meal without prebiotics before intervention (Cohen d = 0.45; P = 0.007). After 3 wk, compared with the iron group, the following results were observed: 1) Lactobacillus sp. abundances were higher in both prebiotic+iron groups (P < 0.05); 2) Enterobacteriaceae sp. abundances (P = 0.022) and the sum of pathogens (P < 0.001) were lower in the 7.5-g+iron group; 3) the abundance of bacterial toxin-encoding genes was lower in the 3-g+iron group (false discovery rate < 0.05); 4) fecal pH (P < 0.001) and calprotectin (P = 0.033) were lower in the 7.5-g+iron group. CONCLUSIONS: Adding prebiotics to iron-fortified infant cereal increases iron absorption and reduces the adverse effects of iron on the gut microbiome and inflammation in Kenyan infants. This trial was registered at clinicaltrials.gov as NCT03894358.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Microbioma Gastrointestinal , Humanos , Lactante , Inflamación , Hierro , Isótopos de Hierro , Isótopos , Kenia , Oligosacáridos/farmacología , PrebióticosRESUMEN
Immune system development during gestation and suckling is significantly modulated by maternal environmental and dietary factors. Breastfeeding is widely recognized as the optimal source of nutrition for infant growth and immune maturation, and its composition can be modulated by the maternal diet. In the present work, we investigated whether oral supplementation with Bifidobacterium breve M-16V and short-chain galacto-oligosaccharide (scGOS) and long-chain fructo-oligosaccharide (lcFOS) to rat dams during gestation and lactation has an impact on the immune system and microbiota composition of the offspring at day 21 of life. On that day, blood, adipose tissue, small intestine (SI), mesenteric lymph nodes (MLN), salivary gland (SG), cecum, and spleen were collected. Synbiotic supplementation did not affect the overall body or organ growth of the pups. The gene expression of Tlr9, Muc2, IgA, and Blimp1 were upregulated in the SI, and the increase in IgA gene expression was further confirmed at the protein level in the gut wash. Synbiotic supplementation also positively impacted the microbiota composition in both the small and large intestines, resulting in higher proportions of Bifidobacterium genus, among others. In addition, there was an increase in butanoic, isobutanoic, and acetic acid concentrations in the cecum but a reduction in the small intestine. At the systemic level, synbiotic supplementation resulted in higher levels of immunoglobulin IgG2c in plasma, SG, and MLN, but it did not modify the main lymphocyte subsets in the spleen and MLN. Overall, synbiotic maternal supplementation is able to positively influence the immune system development and microbiota of the suckling offspring, particularly at the gastrointestinal level.
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Animales Lactantes , Bifidobacterium breve , Suplementos Dietéticos , Microbioma Gastrointestinal , Oligosacáridos , Simbióticos , Animales , Simbióticos/administración & dosificación , Femenino , Embarazo , Ratas , Fenómenos Fisiologicos Nutricionales Maternos , Lactancia , Sistema Inmunológico , Masculino , Animales Recién NacidosRESUMEN
Immunonutrition, which focuses on specific nutrients in breast milk and post-weaning diets, plays a crucial role in supporting infants' immune system development. This study explored the impact of maternal supplementation with Bifidobacterium breve M-16V and a combination of short-chain galacto-oligosaccharide (scGOS) and long-chain fructo-oligosaccharide (lcFOS) from pregnancy through lactation, extending into the early childhood of the offspring. The synbiotic supplementation's effects were examined at both mucosal and systemic levels. While the supplementation did not influence their overall growth, water intake, or food consumption, a trophic effect was observed in the small intestine, enhancing its weight, length, width, and microscopic structures. A gene expression analysis indicated a reduction in FcRn and Blimp1 and an increase in Zo1 and Tlr9, suggesting enhanced maturation and barrier function. Intestinal immunoglobulin (Ig) A levels remained unaffected, while cecal IgA levels decreased. The synbiotic supplementation led to an increased abundance of total bacteria and Ig-coated bacteria in the cecum. The abundance of Bifidobacterium increased in both the intestine and cecum. Short-chain fatty acid production decreased in the intestine but increased in the cecum due to the synbiotic supplementation. Systemically, the Ig profiles remained unaffected. In conclusion, maternal synbiotic supplementation during gestation, lactation, and early life is established as a new strategy to improve the maturation and functionality of the gastrointestinal barrier. Additionally, it participates in the microbiota colonization of the gut, leading to a healthier composition.
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Introduction: Maternal synbiotic supplementation during pregnancy and lactation can significantly influence the immune system. Prebiotics and probiotics have a positive impact on the immune system by preventing or ameliorating among others intestinal disorders. This study focused on the immunomodulatory effects of B. breve M-16V and short chain galacto-oligosaccharides (scGOS)/long chain fructo-oligosachairdes (lcFOS), including systemic and mucosal compartments and milk composition. Methods: Lewis rats were orally administered with the synbiotic or vehicle during pregnancy (21 days) and lactation (21 days). At the weaning day, small intestine (SI), mammary gland (MG), adipose tissue, milk, mesenteric lymph nodes (MLN), salivary gland (SG), feces and cecal content were collected from the mothers. Results: The immunoglobulinome profile showed increased IgG2c in plasma and milk, as well as elevated sIgA in feces at weaning. The supplementation improved lipid metabolism through enhanced brown adipose tissue activity and reinforced the intestinal barrier by increasing the expression of Muc3, Cldn4, and Ocln. The higher production of short chain fatty acids in the cecum and increased Bifidobacterium counts suggest a potential positive impact on the gastrointestinal tract. Discussion: These findings indicate that maternal synbiotic supplementation during gestation and lactation improves their immunological status and improved milk composition.
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Bifidobacterium breve , Lactancia , Leche , Oligosacáridos , Animales , Femenino , Embarazo , Bifidobacterium breve/inmunología , Leche/inmunología , Leche/química , Ratas , Ratas Endogámicas Lew , Suplementos Dietéticos , Simbióticos/administración & dosificación , Probióticos/administración & dosificación , Probióticos/farmacologíaRESUMEN
Optimal functioning of the immune system is crucial to human health, and nutrition is one of the major exogenous factors modulating different aspects of immune function. Currently, no single marker is available to predict the effect of a dietary intervention on different aspects of immune function. To provide further guidance on the assessment and interpretation of the modulation of immune functions due to nutrition in the general population, International Life Sciences Institute Europe commissioned a group of experts from academia, government and the food industry to prepare a guidance document. A draft of this paper was refined at a workshop involving additional experts. First, the expert group defined criteria to evaluate the usefulness of immune function markers. Over seventy-five markers were scored within the context of three distinct immune system functions: defence against pathogens; avoidance or mitigation of allergy; control of low-grade (metabolic) inflammation. The most useful markers were subsequently classified depending on whether they by themselves signify clinical relevance and/or involvement of immune function. Next, five theoretical scenarios were drafted describing potential changes in the values of markers compared with a relevant reference range. Finally, all elements were combined, providing a framework to aid the design and interpretation of studies assessing the effects of nutrition on immune function. This stepwise approach offers a clear rationale for selecting markers for future trials and provides a framework for the interpretation of outcomes. A similar stepwise approach may also be useful to rationalise the selection and interpretation of markers for other physiological processes critical to the maintenance of health and well-being.
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Biomarcadores , Hipersensibilidad , Sistema Inmunológico/fisiología , Infecciones , Inflamación , Fenómenos Fisiológicos de la Nutrición , Evaluación de Resultado en la Atención de Salud/métodos , Guías como Asunto , Estado de Salud , Humanos , Hipersensibilidad/dietoterapia , Hipersensibilidad/inmunología , Infecciones/dietoterapia , Infecciones/inmunología , Inflamación/dietoterapia , Inflamación/inmunología , Proyectos de InvestigaciónRESUMEN
The gut microbiota evolves rapidly after birth, responding dynamically to environmental factors and playing a key role in short- and long-term health. Lifestyle and rurality have been shown to contribute to differences in the gut microbiome, including Bifidobacterium levels, between infants. We studied the composition, function and variability of the gut microbiomes of 6- to 11-month-old Kenyan infants (n = 105). Shotgun metagenomics showed Bifidobacterium longum to be the dominant species. A pangenomic analysis of B. longum in gut metagenomes revealed a high prevalence of B. longum subsp. infantis (B. infantis) in Kenyan infants (80%), and possible co-existence of this subspecies with B. longum subsp. longum. Stratification of the gut microbiome into community (GMC) types revealed differences in composition and functional features. GMC types with a higher prevalence of B. infantis and abundance of B. breve also had a lower pH and a lower abundance of genes encoding pathogenic features. An analysis of human milk oligosaccharides (HMOs) classified the human milk (HM) samples into four groups defined on the basis of secretor and Lewis polymorphisms revealed a higher prevalence of HM group III (Se+, Le-) (22%) than in most previously studied populations, with an enrichment in 2'-fucosyllactose. Our results show that the gut microbiome of partially breastfed Kenyan infants over the age of six months is enriched in bacteria from the Bifidobacterium community, including B. infantis, and that the high prevalence of a specific HM group may indicate a specific HMO-gut microbiome association. This study sheds light on gut microbiome variation in an understudied population with limited exposure to modern microbiome-altering factors.
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Microbioma Gastrointestinal , Leche Humana , Humanos , Lactante , Leche Humana/química , Microbioma Gastrointestinal/genética , Kenia/epidemiología , Oligosacáridos , Bifidobacterium/genéticaRESUMEN
The African region encompasses the highest undernutrition burden with the highest neonatal and infant mortality rates globally. Under these circumstances, breastfeeding is one of the most effective ways to ensure child health and development. However, evidence on human milk (HM) composition from African women is scarce. This is of special concern, as we have no reference data from HM composition in the context of food insecurity in Africa. Furthermore, data on the evolution of HM across lactational stages in this setting lack as well. In the MITICA study, we conducted a cohort study among 48 Central-African women and their 50 infants to analyze the emergence of gut dysbiosis in infants and describe the mother-infant transmission of microbiota between birth and 6 months of age. In this context, we assessed nutritional components in HM of 48 lactating women in Central Africa through five sampling times from week 1 after birth until week 25. Unexpectedly, HM-type III (Secretor + and Lewis genes -) was predominant in HM from Central African women, and some nutrients differed significantly among HM-types. While lactose concentration increased across lactation periods, fatty acid concentration did not vary significantly. The overall median level of 16 detected individual human milk oligosaccharides (HMOs; core structures as well as fucosylated and sialylated ones) decreased from 7.3 g/l at week 1 to 3.5 g/l at week 25. The median levels of total amino acids in HM dropped from 12.8 mg/ml at week 1 to 7.4 mg/ml at week 25. In contrast, specific free amino acids increased between months 1 and 3 of lactation, e.g., free glutamic acid, glutamine, aspartic acid, and serine. In conclusion, HM-type distribution and certain nutrients differed from Western mother HM.
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Although the World Health Organization (WHO) and UNICEF recommend that infants should be exclusively breastfed for the first 6 months of life, evidence is scarce on how the mother's undernourishment status at delivery and maternal dietary factors influence human milk (HM) composition during the first 6 months of life in regions with high food insecurity. The maternal undernourishment status at delivery, maternal diet, and HM nutrients were assessed among 46 women and their 48 vaginally born infants in Bangui at 1, 4, 11, 18, and 25 weeks after birth through 24-h recalls and food consumption questionnaires from December 2017 to June 2019 in the context of the "Mother-to-Infant TransmIssion of microbiota in Central-Africa" (MITICA) study. High food insecurity indexes during the follow-up were significantly associated with them having lower levels of many of the human milk oligosaccharides (HMOs) that were measured and with lower levels of retinol (aß-coef = −0.2, p value = 0.04), fatty acids (aß-coef = −7.2, p value = 0.03), and amino acids (aß-coef = −2121.0, p value < 0.001). On the contrary, women from food-insecure households displayed significantly higher levels of lactose in their HM (aß-coef = 3.3, p value = 0.02). In parallel, the consumption of meat, poultry, and fish was associated with higher HM levels of many of the HMOs that were measured, total amino acids (aß-coef = 5484.4, p value < 0.001), and with lower HM levels of lactose (aß-coef = −15.6, p value = 0.01). Food insecurity and maternal diet had a meaningful effect on HM composition with a possible impact being an infant undernourishment risk. Our results plead for consistent actions on food security as an effective manner to influence the nutritional content of HM and thereby, potentially improve infant survival and healthy growth.
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Lactosa , Leche Humana , Femenino , Humanos , Lactante , Aminoácidos/metabolismo , Lactancia Materna , República Centroafricana , Dieta , Ácidos Grasos/metabolismo , Inseguridad Alimentaria , Lactosa/análisis , Leche Humana/química , Oligosacáridos/análisis , Vitamina A/metabolismoRESUMEN
BACKGROUND: Recent changes in Egyptian dietary habits can be attributed to more urban and sedentary lifestyles and to alterations in the dietary and economic context. The mean BMI of Egyptian women is one of the highest worldwide, and 50% have iron deficiency. OBJECTIVE: The aim was to quantify food and nutrient intakes of urban Egyptian women and conduct a detailed analysis of micronutrients commonly consumed in inadequate amounts, such as iron, vitamin D, and folate. METHODS: Urban Egyptian women aged 19-30 y (n = 130) were recruited during 2016-2017. Energy needs were estimated using the Henry equation, assuming a low physical activity level (1.4). Dietary intakes and iron bioavailability were estimated from a 4-d food diary. Macronutrient intakes were compared with WHO/FAO population goals and micronutrient intakes with Egyptian recommendations. Iron needs were determined for each subject. RESULTS: The mean BMI (kg/m2) was 27.9 ± 4.9. The mean total energy intake (TEI; 2389 ± 715 kcal/d) was significantly higher than needs (2135 ± 237 kcal/d; P = 0.00018). Total fat (33%TEI) and SFA (11%TEI) intakes were slightly higher than population goals (15-30%TEI and <10%TEI, respectively). Diets provided 18 ± 8 g/d of fiber, 98 ± 54 g/d of total sugars, and nearly twice the recommended sodium intake (intake: 2787 ± 1065 mg/d; recommendation: <1500 mg/d). Estimated dietary iron bioavailability was low (9.2% ± 1.6%), and 79% of women consumed less iron than the average requirement (17.5 ± 7 mg/d). Overall, 82% and 80% of women consumed less vitamin D and folate, respectively, than recommended. CONCLUSIONS: Egyptian women aged 19-30 y have high intakes of energy and sodium, whereas iron, vitamin D, and folate intakes are insufficient, with only low concentrations of bioavailable iron. These results call for further investigation into measures that would improve this population's diet quality.
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Enteric infections remain a major health problem causing millions of deaths in developing countries. The interplay among the host intestinal epithelium, the mucosa-associated immune system and microbiota performs an essential role in gut homeostasis and protection against infectious diseases. Dendritic cells (DCs) play a key role in orchestrating protective immunity and tolerance in the gut. The mechanisms by which DCs adapt their responses and discriminate between virulent microbes and trillions of innocuous bacteria remain ill-defined. Here we investigated the effect of cross-talk between commensal-related bacteria (CB) and Toll-like receptor (TLR) agonists on DC activation and the outcome of the in vitro T helper response. Human monocyte-derived DCs were exposed to eight different Gram-positive or Gram-negative CB strains prior to activation with five different TLR agonists. The key polarizing cytokines interleukin (IL)-12p70, IL-10, IL-1beta and IL-6 were quantified and the fate of naïve T-cell differentiation was evaluated. We identified a unique combination of Lactobacillus casei and TLR3 signals that acted in synergy to selectively increase IL-12p70 secretion. Exposure to poly(I:C) converted L. casei-treated DCs into potent promoters of T helper type 1 (Th1) responses. We propose that DCs can integrate harmless and dangerous non-self signals delivered by viral products, to mount robust Th1 responses. Thus, in vivo DC targeting with selective probiotics may improve strategies for the management of enteric diseases.
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Células Dendríticas/inmunología , Interleucina-12/biosíntesis , Intestinos/inmunología , Lacticaseibacillus casei/inmunología , Probióticos , Células TH1/inmunología , Receptor Toll-Like 3/agonistas , Células Dendríticas/efectos de los fármacos , Células Dendríticas/microbiología , Flagelina/inmunología , Humanos , Inductores de Interferón/farmacología , Interleucina-10/biosíntesis , Interleucina-12/agonistas , Interleucina-12/inmunología , Interleucina-1beta/biosíntesis , Interleucina-1beta/inmunología , Interleucina-6/biosíntesis , Intestinos/microbiología , Lipopolisacáridos/inmunología , Peptidoglicano/inmunología , Poli I-C/farmacología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Acetato de Tetradecanoilforbol/farmacología , Células TH1/efectos de los fármacos , Células TH1/microbiología , Receptor Toll-Like 3/metabolismoRESUMEN
Dendritic cells (DCs) orchestrate the immune response establishing immunity versus tolerance. These two opposite functions may be dictated by DC maturation status with maturity linked to immunogenicity. DCs directly interact with trillions of noninvasive intestinal bacteria in vivo, a process that contributes to gut homeostasis. We here evaluated the maturation program elicited in human DCs by direct exposure to commensal-related bacteria (CB) in the absence of inflammatory signals. We showed that eight gram(+) and gram(-) CB strains up-regulated costimulatory molecule expression in DCs and provoked a chemokine receptor switch similar to that activated by gram(+) pathogens. CB strains may be classified into three groups according to DC cytokine release: high IL-12 and low IL-10; low IL-12 and high IL-10; and low IL-12 and IL-10. All CB-treated DCs produced IL-1beta and IL-6 and almost no TGF-beta. Yet, CB instructed DCs to convert naive CD4+ T cells into hyporesponsive T cells that secreted low or no IFN-gamma, IL-10, and IL-17 and instead, displayed suppressor function. These data demonstrate that phenotypic DC maturation combined to an appropriate cytokine profile is insufficient to warrant Th1, IL-10-secreting T regulatory Type 1 (Tr1), or Th17 polarization. We propose that commensal flora and as such, probiotics manipulate DCs by a yet-unidentified pathway to enforce gut tolerance.
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Células Dendríticas/inmunología , Células Dendríticas/microbiología , Lacticaseibacillus casei/inmunología , Linfocitos T Reguladores/inmunología , Formación de Anticuerpos , Técnicas de Cultivo de Célula , Citometría de Flujo , Humanos , Terapia de Inmunosupresión , Interleucina-10/metabolismo , Interleucina-12/metabolismo , Expansión de TejidoRESUMEN
Serum ferritin concentration is the preferred biomarker to assess population iron status in the absence of inflammation. Interpretation of this biomarker is complicated in populations with a high burden of infection, however, because inflammation increases serum ferritin concentration independently of iron status. We aimed to compare estimates of iron status of Kenyan pregnant women, with circulating ferritin concentrations adjusted for inflammation using newly proposed methods by the BRINDA project, or using previously proposed adjustment methods. We re-analyzed data from pregnant Kenyan women living in a rural area where malaria is highly endemic (n = 470) or in an urban area (n = 402). As proposed by the BRINDA group, we adjusted individual ferritin concentration by internal regression for circulating concentrations of C-reactive protein (CRP) and α1-acid glycoprotein (AGP). Other adjustment methods comprised: (a) arithmetic correction factors based on CRP or AGP; (b) exclusion of subjects with inflammation (CRP >5 mg/L or AGP >1 g/L); and (c) higher ferritin cut-off value (<30 µg/L). We additionally adjusted for Plasmodium infection as appropriate. Lastly, we assessed iron status without adjustment for inflammation. All correction methods increased prevalence of iron deficiency compared to the unadjusted estimates. This increase was more pronounced with the internal regression correction method. The iron deficiency prevalence estimate increased from 53% to 87% in rural Kisumu study and from 30% to 41% in the urban Nairobi study after adjusting for inflammation (CRP and AGP) using the BRINDA internal regression method. When we corrected for both inflammation and Plasmodium infection using the regression correction, it resulted in lower prevalence estimates compared to uninfected women. Application of linear regression methods to adjust circulating ferritin concentration for inflammation leads to markedly decreased point estimates for ferritin concentration and increased estimates for the prevalence of iron deficiency in pregnancy.
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Anemia Ferropénica/epidemiología , Ferritinas/sangre , Inflamación/sangre , Deficiencias de Hierro , Complicaciones del Embarazo/epidemiología , Adulto , Anemia Ferropénica/sangre , Anemia Ferropénica/etiología , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Femenino , Humanos , Kenia/epidemiología , Malaria/sangre , Malaria/complicaciones , Malaria/epidemiología , Estado Nutricional , Orosomucoide/análisis , Embarazo , Complicaciones del Embarazo/sangre , Complicaciones del Embarazo/etiología , Prevalencia , Análisis de Regresión , Población Rural/estadística & datos numéricos , Población Urbana/estadística & datos numéricos , Adulto JovenRESUMEN
Shigella, the causative agent of bacillary dysentery, invades epithelial cells. Upon bacterial-cell contact, the type III bacterial effector IpaA binds to the cytoskeletal protein vinculin to promote actin reorganization required for efficient bacterial uptake. We show that the last 74 C-terminal residues of IpaA (A559) bind to human vinculin (HV) and promotes its association with actin filaments. Polymerisation experiments demonstrated that A559 was sufficient to induce HV-dependent partial capping of the barbed ends of actin filaments. These results suggest that IpaA regulates actin polymerisation/depolymerisation at sites of Shigella invasion by modulating the barbed end capping activity of vinculin.
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Actinas/metabolismo , Antígenos Bacterianos/química , Antígenos Bacterianos/metabolismo , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Shigella/metabolismo , Vinculina/metabolismo , Actinas/química , Animales , Antígenos Bacterianos/genética , Proteínas Bacterianas/genética , Sitios de Unión , Biopolímeros/química , Biopolímeros/metabolismo , Humanos , Técnicas In Vitro , Cinética , Estructura Terciaria de Proteína , Conejos , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Eliminación de Secuencia , Shigella/genética , Shigella/patogenicidad , Vinculina/química , Vinculina/genéticaRESUMEN
Scientific experts from nine countries gathered to share their views and experience around iron interventions in Africa. Inappropriate eating habits, infections and parasitism are responsible for significant prevalence of iron deficiency, but reliable and country-comparable prevalence estimates are lacking: improvements in biomarkers and cut-offs values adapted to context of use are needed. Benefits of iron interventions on growth and development are indisputable and outweigh risks, which exist in populations with a high infectious burden. Indeed, pathogen growth may increase with enhanced available iron, calling for caution and preventive measures where malaria or other infections are prevalent. Most African countries programmatically fortify flour and supplement pregnant women, while iron deficiency in young children is rather addressed at individual level. Coverage and efficacy could improve through increased access for target populations, raised awareness and lower cost. More bioavailable iron forms, helping to decrease iron dose, or prebiotics, which both may lower risk of infections are attractive opportunities for Africa. Fortifying specific food products could be a relevant route, adapted to local context and needs of population groups while providing education and training. More globally, partnerships involving various stakeholders are encouraged, that could tackle all aspects of the issue.
Asunto(s)
Anemia Ferropénica/dietoterapia , Anemia Ferropénica/tratamiento farmacológico , Anemia Ferropénica/epidemiología , Alimentos Fortificados , Micronutrientes/administración & dosificación , Adolescente , Adulto , África , Preescolar , Suplementos Dietéticos , Femenino , Humanos , Hierro/administración & dosificación , Deficiencias de Hierro , Persona de Mediana Edad , Embarazo , Prevalencia , Adulto JovenRESUMEN
Ageing of the global population has become a public health concern with an important socio-economic dimension. Ageing is characterized by an increase in the concentration of inflammatory markers in the bloodstream, a phenomenon that has been termed "inflammageing". The inflammatory response is beneficial as an acute, transient reaction to harmful conditions, facilitating the defense, repair, turnover and adaptation of many tissues. However, chronic and low grade inflammation is likely to be detrimental for many tissues and for normal functions. We provide an overview of low grade inflammation (LGI) and determine the potential drivers and the effects of the "inflamed" phenotype observed in the elderly. We discuss the role of gut microbiota and immune system crosstalk and the gut-brain axis. Then, we focus on major health complications associated with LGI in the elderly, including mental health and wellbeing, metabolic abnormalities and infections. Finally, we discuss the possibility of manipulating LGI in the elderly by nutritional interventions. We provide an overview of the evidence that exists in the elderly for omega-3 fatty acid, probiotic, prebiotic, antioxidant and polyphenol interventions as a means to influence LGI. We conclude that slowing, controlling or reversing LGI is likely to be an important way to prevent, or reduce the severity of, age-related functional decline and the onset of conditions affecting health and well-being; that there is evidence to support specific dietary interventions as a strategy to control LGI; and that a continued research focus on this field is warranted.
Asunto(s)
Envejecimiento/inmunología , Estado de Salud , Mediadores de Inflamación/inmunología , Estado Nutricional/fisiología , Envejecimiento/metabolismo , Envejecimiento/patología , Antioxidantes/administración & dosificación , Antioxidantes/fisiología , Biomarcadores/metabolismo , Ácidos Grasos Omega-3/administración & dosificación , Ácidos Grasos Omega-3/inmunología , Ácidos Grasos Omega-3/metabolismo , Microbioma Gastrointestinal/fisiología , Humanos , Inflamación/inmunología , Inflamación/metabolismo , Inflamación/patología , Mediadores de Inflamación/metabolismoRESUMEN
Respiratory tract infections such as flu cause severe morbidity and mortality and are among the leading causes of death in children and adults worldwide. Commensal microbiota is critical for orchestrating tissue homeostasis and immunity in the intestine. Probiotics represent an interesting source of immune modulators and several clinical studies have addressed the potential beneficial effects of probiotics against respiratory infections. Therefore, we have investigated the mechanisms of protection conferred by L. paracasei CNCM I-1518 strain in a mouse model of influenza infection. Notably, local myeloid cells accumulation is generated in the lungs after seven days feeding with L. paracasei prior to viral infection. L. paracasei-fed mice showed reduced susceptibility to the influenza infection, associated with less accumulation of inflammatory cells in the lungs, faster viral clearance and general health improvement. Interestingly, Allobaculum was significantly increased in L. paracasei-fed mice 7 days after influenza infection, even if the gut microbiota composition was not altered overall. L. paracasei-purified peptidoglycan partially recapitulated the protective phenotype observed with the entire bacteria. Collectively, our results demonstrate that oral consumption of L. paracasei CNCM I-1518 modulates lung immunity was associated with an improved control of influenza infection. These results further extend the beneficial role for certain lactobacilli to alleviate the burden of respiratory tract infections.