The Relationship between Choline Bioavailability from Diet, Intestinal Microbiota Composition, and Its Modulation of Human Diseases

© 2020 by the authors.Choline is a water-soluble nutrient essential for human life. Gut microbial metabolism of choline results in the production of trimethylamine (TMA), which, upon absorption by the host is converted into trimethylamine-N-oxide (TMAO) in the liver. A high accumulation of both components is related to cardiovascular disease, inflammatory bowel disease, non-alcoholic fatty liver disease, and chronic kidney disease. However, the relationship between the microbiota production of these components and its impact on these diseases still remains unknown. In this review, we will address which microbes contribute to TMA production in the human gut, the extent to which host factors (e.g., the genotype) and diet affect TMA production, and the colonization of these microbes and the reversal of dysbiosis as a therapy for these diseases.This work was supported by the Ministry of Science, Innovation and Universities (PSI2017-83893-R to J.L.A.) and the Ministry of Economy and Business (PSI2015-73111-EXP to J.L.A., PSI2017-90806-REDT to J.L.A. and AGL2017-83653R to M.G.) (Spain). S.A. was the recipient of a postdoctoral Juan de la Cierva Contract (Ministry of Science, Innovation and Universities, Ref. IJCI-2017-32156).Peer reviewe

Magnetic nanostructures for emerging biomedical applications

Magnetic nanostructures have been widely studied due to their potential applicability into several research fields such as data storage, sensing and biomedical applications. Focusing on the biomedical aspect, some new approaches deserve to be mentioned: cell manipulation and separation, contrast-enhancing agents for magnetic resonance imaging, and magnetomechanically induced cell death. This work focuses on understanding three different magnetic nanostructures, disks in the vortex state, synthetic antiferromagnetic particles and nanowires, first, by explaining their interesting properties and how they behave under an applied external field, before reviewing their potential applications for each of the aforementioned techniques.The authors acknowledge funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie Grant Agreement No. 734801. C.R. and R.M. acknowledge funding from Basque Government Grant Nos. PIBA 2018-11 and IT1162-19, and Spanish Grant No. FIS2016-76058 (AEI/FEDER, UE). D.N. acknowledges the Spanish Ministry for Science, Innovation and Universities, for funding through the “Ramon y Cajal” program RYC-2017-22820. C.T. Sousa thanks FCT for financial support through the Investigador FCT program (Contract No. IF/01159/2015). R. Magalhães is grateful to the FCT SFRH/BD/148563/2019 PhD grant. This work was also supported by the Portuguese Fundação para a Ciência e a Tecnologia (FCT) and COMPETE 2020 (FEDER) under the projects POCI-01-0145-FEDER-028676/PTDC/CTM-CTM/28676/2017, POCI-01-0145/FEDER-032257/PTDC/FIS-OTI/32257/2017, POCI-01-0145-FEDER031302/PTDC/FIS-MAC/31302/2017, and POCI-01-0141-FEDER032527

Effect of intrapartum antibiotics prophylaxis on the bifidobacterial establishment within the neonatal gut

Antibiotics are important disruptors of the intestinal microbiota establishment, linked to immune and metabolic alterations. The intrapartum antibiotics prophylaxis (IAP) is a common clinical practice that is present in more than 30% of labours, and is known to negatively affect the gut microbiota composition. However, little is known about how it affects to Bifidobacterium (sub)species level, which is one of the most important intestinal microbial genera early in life. This study presents qualitative and quantitative analyses of the bifidobacterial (sub)species populations in faecal sam-ples, collected at 2, 10, 30 and 90 days of life, from 43 healthy full-term babies, sixteen of them delivered after IAP use. This study uses both 16S rRNA–23S rRNA internal transcribed spacer (ITS) region sequencing and q-PCR techniques for the analyses of the relative proportions and absolute levels, respectively, of the bifidobacterial populations. Our results show that the bifidobacterial populations establishment is affected by the IAP at both quantitative and qualitative levels. This practice can promote higher bifidobacterial diversity and several changes at a compositional level. This study underlines specific targets for developing gut microbiota-based products for favouring a proper bifidobacterial microbiota development when IAP is required

Targeting the microbiota-gut-brain axis: prebiotics have anxiolytic and antidepressant-like effects and reverse the impact of chronic stress in mice

Background: The realization that the microbiota-gut-brain axis plays a critical role in health and disease, including neuropsychiatric disorders, is rapidly advancing. Nurturing a beneficial gut microbiome with prebiotics, such as fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS), is an appealing but underinvestigated microbiota manipulation. Here we tested whether chronic prebiotic treatment modifies behavior across domains relevant to anxiety, depression, cognition, stress response, and social behavior. Methods: C57BL/6J male mice were administered FOS, GOS, or a combination of FOS+GOS for 3 weeks prior to testing. Plasma corticosterone, microbiota composition, and cecal short-chain fatty acids were measured. In addition, FOS+GOS- or water-treated mice were also exposed to chronic psychosocial stress, and behavior, immune, and microbiota parameters were assessed. Results: Chronic prebiotic FOS+GOS treatment exhibited both antidepressant and anxiolytic effects. Moreover, the administration of GOS and the FOS+GOS combination reduced stress-induced corticosterone release. Prebiotics modified specific gene expression in the hippocampus and hypothalamus. Regarding short-chain fatty acid concentrations, prebiotic administration increased cecal acetate and propionate and reduced isobutyrate concentrations, changes that correlated significantly with the positive effects seen on behavior. Moreover, FOS+GOS reduced chronic stress-induced elevations in corticosterone and proinflammatory cytokine levels and depression-like and anxiety-like behavior in addition to normalizing the effects of stress on the microbiota. Conclusions: Taken together, these data strongly suggest a beneficial role of prebiotic treatment for stress-related behaviors. These findings strengthen the evidence base supporting therapeutic targeting of the gut microbiota for brain-gut axis disorders, opening new avenues in the field of nutritional neuropsychopharmacology

Donated human milk as a determinant factor for the gut bifidobacterial ecology in premature babies

Correct establishment of the gut microbiome is compromised in premature babies, with Bifidobacterium being one of the most affected genera. Prematurity often entails the inability to successfully breastfeed, therefore requiring the implementation of other feeding modes; breast milk expression from a donor mother is the recommended option when their own mother’s milk is not available. Some studies showed different gut microbial profiles in premature infants fed with breast milk and donor human milk, however, it is not known how this affects the species composition of the genus Bifidobacterium. The objective of this study was to assess the effect of donated human milk on shaping the gut bifidobacterial populations of premature babies during the first three months of life. We analyzed the gut bifidobacterial communities of 42 premature babies fed with human donor milk or own-mother milk by the 16S rRNA-23S rRNA internal transcriber spaces (ITS) region sequencing and q-PCR. Moreover, metabolic activity was assessed by gas chromatography. We observed a specific bifidobacterial profile based on feeding type, with higher bifidobacterial diversity in the human donor milk group. Differences in specific Bifidobacterium species composition may contribute to the development of specific new strategies or treatments aimed at mimicking the impact of own-mother milk feeding in neonatal units

In vitro evaluation of different prebiotics on the modulation of gut microbiota composition and function in morbid obese and normal-weight subjects

The gut microbiota remains relatively stable during adulthood; however, certain intrinsic and environmental factors can lead to microbiota dysbiosis. Its restoration towards a healthy condition using best-suited prebiotics requires previous development of in vitro models for evaluating their functionality. Herein, we carried out fecal cultures with microbiota from healthy normal-weight and morbid obese adults. Cultures were supplemented with different inulin-type fructans (1-kestose, Actilight, P95, Synergy1 and Inulin) and a galactooligosaccharide. Their impact on the gut microbiota was assessed by monitoring gas production and evaluating changes in the microbiota composition (qPCR and 16S rRNA gene profiling) and metabolic activity (gas chromatography). Additionally, the effect on the bifidobacterial species was assessed (ITS-sequencing). Moreover, the functionality of the microbiota before and after prebiotic-modulation was determined in an in vitro model of interaction with an intestinal cell line. In general, 1-kestose was the compound showing the largest effects. The modulation with prebiotics led to significant increases in the Bacteroides group and Faecalibacterium in obese subjects, whereas in normal-weight individuals, substantial rises in Bifidobacterium and Faecalibacterium were appreciated. Notably, the results obtained showed differences in the responses among the tested compounds but also among the studied human populations, indicating the need for developing population-specific products

Factors influencing gastrointestinal tract and microbiota immune interaction in preterm infants

The role of microbial colonization is indispensable for keeping a balanced immune response in life. However, the events that regulate the establishment of the microbiota, their timing, and the way in which they interact with the host are not yet fully understood. Factors such as gestational age, mode of delivery, environment, hygienic measures, and diet influence the establishment of microbiota in the perinatal period. Environmental microbes constitute the most important group of exogenous stimuli in this critical time frame. However, the settlement of a stable gut microbiota in preterm infants is delayed compared to term infants. Preterm infants have an immature gastrointestinal tract and immune system which predisposes to infectious morbidity. Neonatal microbial dynamics and alterations in early gut microbiota may precede and/or predispose to diseases such as necrotizing enterocolitis (NEC), late-onset sepsis or others. During this critical period, nutrition is the principal contributor for immunological and metabolic development, and microbiological programming. Breast milk is a known source of molecules that act synergistically to protect the gut barrier and enhance the maturation of the gut-related immune response. Host-microbe interactions in preterm infants and the protective role of diet focused on breast milk impact are beginning to be unveiled.M.C. acknowledges a “Rio Hortega” Research Fellowship Grant (CM13/0017) and M.V. acknowledges grants PI11/0313 and RD12/0026/0012 (Red SAMID) from the Instituto Carlos III (Spanish Ministry of Economy and Competitivity). M.C.C. and G.P-M. were supported by the grant AGL2013-47420-R from the Spanish Ministry of Science and Innovation.Peer reviewe

Diversity of Bifidobacteria within the Infant Gut Microbiota

Background The human gastrointestinal tract (GIT) represents one of the most densely populated microbial ecosystems studied to date. Although this microbial consortium has been recognized to have a crucial impact on human health, its precise composition is still subject to intense investigation. Among the GIT microbiota, bifidobacteria represent an important commensal group, being among the first microbial colonizers of the gut. However, the prevalence and diversity of members of the genus Bifidobacterium in the infant intestinal microbiota has not yet been fully characterized, while some inconsistencies exist in literature regarding the abundance of this genus. Methods/Principal Findings In the current report, we assessed the complexity of the infant intestinal bifidobacterial population by analysis of pyrosequencing data of PCR amplicons derived from two hypervariable regions of the 16 S rRNA gene. Eleven faecal samples were collected from healthy infants of different geographical origins (Italy, Spain or Ireland), feeding type (breast milk or formula) and mode of delivery (vaginal or caesarean delivery), while in four cases, faecal samples of corresponding mothers were also analyzed. Conclusions In contrast to several previously published culture-independent studies, our analysis revealed a predominance of bifidobacteria in the infant gut as well as a profile of co-occurrence of bifidobacterial species in the infant’s intestine

Immune Response to Bifidobacterium bifidum Strains Support Treg/Th17 Plasticity

In this work we analyzed the immune activation properties of different Bifidobacterium strains in order to establish their ability as inductors of specific effector (Th) or regulatory (Treg) responses. First, we determined the cytokine pattern induced by 21 Bifidobacterium strains in peripheral blood mononuclear cells (PBMCs). Results showed that four Bifidobacterium bifidum strains showed the highest production of IL-17 as well as a poor secretion of IFNγ and TNFα, suggesting a Th17 profile whereas other Bifidobacterium strains exhibited a Th1-suggestive profile. Given the key role of Th17 subsets in mucosal defence, strains suggestive of Th17 responses and the putative Th1 Bifidobacterium breve BM12/11 were selected to stimulate dendritic cells (DC) to further determine their capability to induce the differentiation of naïve CD4+ lymphocytes toward different Th or Treg cells. All selected strains were able to induce phenotypic DC maturation, but showed differences in cytokine stimulation, DC treated with the putative Th17 strains displaying high IL-1β/IL-12 and low IL-12/IL-10 index, whereas BM12/11-DC exhibited the highest IL-12/IL-10 ratio. Differentiation of naïve lymphocytes confirmed Th1 polarization by BM12/11. Unexpectedly, any B. bifidum strain showed significant capability for Th17 generation, and they were able to generate functional Treg, thus suggesting differences between in vivo and vitro responses. In fact, activation of memory lymphocytes present in PBMCS with these bacteria, point out the presence in vivo of specific Th17 cells, supporting the plasticity of Treg/Th17 populations and the key role of commensal bacteria in mucosal tolerance and T cell reprogramming when needed

Crustal thickness and velocity structure across the Moroccan Atlas from long offset wide-angle reflection seismic data: The SIMA experiment

The crustal structure and topography of the Moho boundary beneath the Atlas Mountains of Morocco has been constrained by a controlled source, wide-angle seismic reflection transect: the SIMA experiment. This paper presents the first results of this project, consisting of an almost 700 km long, high-resolution seismic profile acquired from the Sahara craton across the High and the Middle Atlas and the Rif Mountains. The interpretation of this seismic data set is based on forward modeling by raytracing, and has resulted in a detailed crustal structure and velocity model for the Atlas Mountains. Results indicate that the High Atlas features a moderate crustal thickness, with the Moho located at a minimum depth of 35 km to the S and at around 31 km to the N, in the Middle Atlas. Upper crustal shortening is resolved at depth through a crustal root where the Saharan crust underthrusts the northern Moroccan crust. This feature defines a lower crust imbrication that, locally, places the Moho boundary at 40-41 km depth in the northern part of the High Atlas. The P-wave velocity model is characterized by relatively low velocities, mostly in the lower crust and upper mantle, when compared to other active orogens and continental regions. These low deep crustal velocities together with other geophysical observables such as conductivity estimates derived from MT measurements, moderate Bouguer gravity anomaly, high heat flow, and surface exposures of recent alkaline volcanism lead to a model where partial melts are currently emplaced at deep crustal levels and in the upper mantle. The resulting model supports the existence of a mantle upwelling as mechanism that would contribute significantly to sustain the High Atlas topography. However, the detailed Moho geometry deduced in this work should lead to a revision of the exact geometry and position of this mantle feature and will require new modeling effortsThis work has been primarily funded by the Spanish MEC project CGL2007–63889. Additional funding was provided by projects CGL2010–15416, CSD2006-00041, and GL2009–09727 (Spain), CGL2008–03474-E, 07-TOPO_EUROPE_FP-006 (ESF Eurocores) and EAR-0808939 (US, NSF).Peer reviewe