Maternal gut Bifidobacterium breve modifies fetal brain metabolism in germ-free mice

Background: Recent advances have significantly expanded our understanding of the gut microbiome's influence on host physiology and metabolism. However, the specific role of certain microorganisms in gestational health and fetal development remains underexplored. Objective: This study investigates the impact of Bifidobacterium breve UCC2003 on fetal brain metabolism when colonized in the maternal gut during pregnancy. Methods: Germ-free pregnant mice were colonized with or without B. breve UCC2003 during pregnancy. The metabolic profiles of fetal brains were analyzed, focusing on the presence of key metabolites and the expression of critical metabolic and cellular pathways. Results: Maternal colonization with B. breve resulted in significant metabolic changes in the fetal brain. Specifically, ten metabolites, including citrate, 3-hydroxyisobutyrate, and carnitine, were reduced in the fetal brain. These alterations were accompanied by increased abundance of transporters involved in glucose and branched-chain amino acid uptake. Furthermore, supplementation with this bacterium was associated with elevated expression of critical metabolic pathways such as PI3K-AKT, AMPK, STAT5, and Wnt-β-catenin signaling, including its receptor Frizzled-7. Additionally, there was stabilization of HIF-2 protein and modifications in genes and proteins related to cellular growth, axogenesis, and mitochondrial function. Conclusions: The presence of maternal B. breve during pregnancy plays a crucial role in modulating fetal brain metabolism and growth. These findings suggest that Bifidobacterium could modify fetal brain development, potentially offering new avenues for enhancing gestational health and fetal development through microbiota-targeted interventions

Chloroplast genomes as a tool to resolve red algal phylogenies: a case study in the Nemaliales

Obtaining strongly supported phylogenies that permit confident taxonomic and evolutionary interpretations has been a challenge in algal biology. High-throughput sequencing has improved the capacity to generate data and yields more informative datasets. We sequenced and analysed the chloroplast genomes of 22 species of the order Nemaliales as a case study in the use of phylogenomics as an approach to achieve well-supported phylogenies of red algae.Australian Research Council/[FT110100585]/ARC/AustraliaAustralian Biological Resources Study/[RFL213-08]/ABRS/AustraliaMillennium Scientific Initiative/[NC120030]/MSI/Nueva JerseyUniversity of Melbourne///AustraliaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigación en Ciencias del Mar y Limnología (CIMAR

Robust method of metrology for direct phase measurement for nano-antennas

Optical metasurfaces allow the development of original and more and more complex optical functions. They are therefore facing a design and characterization problem. Indeed, they are more and more composed of complex patterns, with different types of antennas and non-periodic. This is why it is important to build libraries of nano-structures that can be used as building blocks to compose optical functions. Therefore, we propose a direct phase measurement metrology method for optical nanostructures. Using lateral shift interferometry, our technique allows to simultaneously characterize in amplitude and phase nano-antennas of all types, shapes and materials, and thus to experimentally establish a library of nano-antennas. Our method brings an additional tool in the design of nano-antennas, which completes the existing simulation tools, by allowing to test all types of nano-antennas

Maternal short chain fructo-oligosaccharides supplementation during late gestation and lactation influences milk components and offspring gut metabolome: a pilot study

Abstract Breast milk composition is influenced by maternal diet. This study aimed to evaluate if supplementation of maternal diet with a prebiotic fibre, through its potential effect on milk composition, can be a leverage to orientate the gut microbiota of infants in a way that would be beneficial for their health. Twelve sows received a diet supplemented with short chain fructo-oligosaccharides or maltodextrins during the last month of gestation and the lactation. Oligosaccharidic and lipidomic profiles of colostrum and mature milk (21 days), as well as faecal microbiota composition and metabolomic profile of 21 day-old piglets were evaluated. The total porcine milk oligosaccharide concentration tended to be lower in scFOS-supplemented sows, mainly due to the significant reduction of the neutral core oligosaccharides (in particular that of a tetrahexose). Maternal scFOS supplementation affected the concentration of 31 lipids (mainly long-chain triglycerides) in mature milk. Faecal short-chain fatty acid content and that of 16 bacterial metabolites were modified by scFOS supplementation. Interestingly, the integrative data analysis gave a novel insight into the relationships between (i) maternal milk lipids and PMOs and (ii) offspring faecal bacteria and metabolites. In conclusion, scFOS-enriched maternal diet affected the composition of mature milk, and this was associated with a change in the colonisation of the offspring intestinal microbiota

Maternal gut Bifidobacterium breve modifies fetal brain metabolism in germ-free mice.

BACKGROUND: Recent advances have significantly expanded our understanding of the gut microbiome's influence on host physiology and metabolism. However, the specific role of certain microorganisms in gestational health and fetal development remains underexplored. OBJECTIVE: This study investigates the impact of Bifidobacterium breve UCC2003 on fetal brain metabolism when colonized in the maternal gut during pregnancy. METHODS: Germ-free pregnant mice were colonized with or without Bifidobacterium breve UCC2003 during pregnancy. The metabolic profiles of fetal brains were analyzed, focusing on the presence of key metabolites and the expression of critical metabolic and cellular pathways. RESULTS: Maternal colonization with Bifidobacterium breve resulted in significant metabolic changes in the fetal brain. Specifically, ten metabolites, including citrate, 3-hydroxyisobutyrate, and carnitine, were reduced in the fetal brain. These alterations were accompanied by increased abundance of transporters involved in glucose and branched-chain amino acid uptake. Furthermore, supplementation with this bacterium was associated with elevated expression of critical metabolic pathways such as PI3K-AKT, AMPK, STAT5, and Wnt-β-catenin signaling, including its receptor Frizzled-7. Additionally, there was stabilization of HIF-2 protein and modifications in genes and proteins related to cellular growth, axogenesis, and mitochondrial function. CONCLUSIONS: The presence of maternal Bifidobacterium breve during pregnancy plays a crucial role in modulating fetal brain metabolism and growth. These findings suggest that Bifidobacterium could modify fetal brain development, potentially offering new avenues for enhancing gestational health and fetal development through microbiota-targeted interventions.This work was supported by (JL-T) Sir Henry Wellcome Postdoctoral Fellowship (220456/Z/20/Z), Newton International Fellowship from the Royal Society (NF170988 / RG90199) and Attraction of Talent Grant from the Community of Madrid (grant No.. 2023-T1/SAL-GL-28960, CESAR NOMBELA fellowship). L.J.H. is supported by Wellcome Trust Investigator Award 220876/Z/20/Z; the Biotechnology and Biological Sciences Research Council (BBSRC), Institute Strategic Programme Gut Microbes and Health BB/R012490/1, and its constituent projects BBS/E/F/000PR10353 and BBS/E/F/000PR10356, and the BBSRC Institute Strategic Programme Food Microbiome and Health BB/X011054/1 and its constituent project BBS/E/F/000PR13631. ANS-P is supported by a Lister Institute of Preventative Medicine Research Prize (RG93692). DvS is a member of the APC Microbiome Ireland research centre funded by Science Foundation Ireland (SFI) through the Irish Government’s National Development Plan (Grant numbers SFI/12/RC/2273a and SFI/12/RC/2273b)

Modifications des recommandations de la Haute Autorité de santé concernant le diagnostic de la dénutrition : application par les professionnels de la nutrition en pratique clinique

International audienceIntroduction: The new diagnostic criteria of the french health authority (HAS) for undernutrition suggest assessing patients’ muscle strength and/or mass. The methods are less available in practice. Albumin levels are now considered as a criterion for the severity of undernutrition. Our aim was to assess the impact of these changes in recommendations on the practices of professionals involved in screening for and diagnosing undernutrition. Materials and methods: The Scientific Advisory Board of the french speaking society for clinical nutrition and metabolism (SFNCM) used google forms® to conduct an e-mail survey of the society's members. Results: We obtained 363 responses. Eighty-seven percent and 77% of respondents respectively stated that they rarely or never assess muscle mass or strength. A minority of professionals said they were equipped to carry out these assessments (38% had a dynamometer, 23% an impedancemeter). However, even those had access to them did not use them regularly. With regard to albuminemia, almost half of those questioned said they used it to diagnose malnutrition. Conclusion: Few of the professionals responsible for diagnosing undernutrition are able to assess muscle mass and strength, due to a lack of muscle mass and strength due to a lack of access to techniques. The use of albumin levels as a marker of the severity of undernutrition seems ambiguous to some. The training of teams and funding for equipment would therefore seem to be prerequisites for the successful implementation of these recommendations

Tyrosine kinase inhibitor NVP-BGJ398 functionally improves FGFR3-related dwarfism in mouse model

Achondroplasia (ACH) is the most frequent form of dwarfism and is caused by gain-of-function mutations in the fibroblast growth factor receptor 3-encoding (FGFR3-encoding) gene. Although potential therapeutic strategies for ACH, which aim to reduce excessive FGFR3 activation, have emerged over many years, the use of tyrosine kinase inhibitor (TKI) to counteract FGFR3 hyperactivity has yet to be evaluated. Here, we have reported that the pan-FGFR TKI, NVP-BGJ398, reduces FGFR3 phosphorylation and corrects the abnormal femoral growth plate and calvaria in organ cultures from embryos of the Fgfr3Y367C/+ mouse model of ACH. Moreover, we demonstrated that a low dose of NVP-BGJ398, injected subcutaneously, was able to penetrate into the growth plate of Fgfr3Y367C/+ mice and modify its organization. Improvements to the axial and appendicular skeletons were noticeable after 10 days of treatment and were more extensive after 15 days of treatment that started from postnatal day 1. Low-dose NVP-BGJ398 treatment reduced intervertebral disc defects of lumbar vertebrae, loss of synchondroses, and foramen-magnum shape anomalies. NVP-BGJ398 inhibited FGFR3 downstream signaling pathways, including MAPK, SOX9, STAT1, and PLCγ, in the growth plates of Fgfr3Y367C/+ mice and in cultured chondrocyte models of ACH. Together, our data demonstrate that NVP-BGJ398 corrects pathological hallmarks of ACH and support TKIs as a potential therapeutic approach for ACH

Transposition dans les unités de soin des recommandations de bonne pratique de la Haute Autorité de santé sur le diagnostic de la dénutrition de l'enfant, de l'adulte et de la personne âgée

International audienceObjectives: The French ministry of health and the French federation of nutrition published in 2019 and 2021 updated clinical recommendations around nutritional status assessment in children, adults and elderly people. New definitions of undernutrition were produced based on new criteria and/or new thresholds. The challenge now is to engage with healthcare professionals to implement these into their daily practice. Material and methods: This practical implementation guide uses the established implementation model Pronovost to help implementing these evidence-based clinical recommendations into clinical practice. Results: The Pronovost implementation model of evidence into practice allowed us to provide a practical framework with associated documents and tools to facilitate implementation of these clinical recommendations into healthcare professional practice. The paper is structured around the four steps of the Pronovost model: summary of the evidence; identification of local barriers to implementation; measurement of performance; ensuring all patients receive the intervention. Relevant checklists for implementation and compliance monitoring are proposed, in addition to tables outlining professional respective responsibilities and tasks. Conclusion: Implementation science models like the Pronovost model help implementing clinical recommendations into clinical practices

Tyrosine kinase inhibitor NVP-BGJ398 functionally improves FGFR3-related dwarfism in mouse model

Achondroplasia (ACH) is the most frequent form of dwarfism and is caused by gain-of-function mutations in the fibroblast growth factor receptor 3–encoding (FGFR3-encoding) gene. Although potential therapeutic strategies for ACH, which aim to reduce excessive FGFR3 activation, have emerged over many years, the use of tyrosine kinase inhibitor (TKI) to counteract FGFR3 hyperactivity has yet to be evaluated. Here, we have reported that the pan-FGFR TKI, NVP-BGJ398, reduces FGFR3 phosphorylation and corrects the abnormal femoral growth plate and calvaria in organ cultures from embryos of the Fgfr3(Y367C/+) mouse model of ACH. Moreover, we demonstrated that a low dose of NVP-BGJ398, injected subcutaneously, was able to penetrate into the growth plate of Fgfr3(Y367C/+) mice and modify its organization. Improvements to the axial and appendicular skeletons were noticeable after 10 days of treatment and were more extensive after 15 days of treatment that started from postnatal day 1. Low-dose NVP-BGJ398 treatment reduced intervertebral disc defects of lumbar vertebrae, loss of synchondroses, and foramen-magnum shape anomalies. NVP-BGJ398 inhibited FGFR3 downstream signaling pathways, including MAPK, SOX9, STAT1, and PLCγ, in the growth plates of Fgfr3(Y367C/+) mice and in cultured chondrocyte models of ACH. Together, our data demonstrate that NVP-BGJ398 corrects pathological hallmarks of ACH and support TKIs as a potential therapeutic approach for ACH

Association between ultrasound quadriceps muscle status with premorbid functional status and 60-day mortality in mechanically ventilated critically ill patient: A single-center prospective observational study

Background & aims: In critically ill patients, direct measurement of skeletal muscle using bedside ultrasound (US) may identify a patient population that might benefit more from optimal nutrition practices. When US is not available, survey measures of nutrition risk and functional status that are associated with muscle status may be used to identify patients with low muscularity. This study aims to determine the association between baseline and changing ultrasound quadriceps muscle status with premorbid functional status and 60-day mortality. Methods: This single-center prospective observational study was conducted in a general ICU. Mechanically ventilated critically ill adult patients (age ≥18 years) without pre-existing systemic neuromuscular diseases and expected to stay for ≥96 h in the ICU were included. US measurements were performed within 48 h of ICU admission (baseline), at day 7, day 14 of ICU stay and at ICU discharge (if stay >14 days). Quadriceps muscle layer thickness (QMLT), rectus femoris cross sectional area (RFCSA), vastus intermedius pennation angle (PA) and fascicle length (FL), and rectus femoris echogenicity (mean and standard deviation [SD]) were measured. Patients' next-of-kin were interviewed by using established questionnaires for their pre-hospitalization nutritional risk (nutrition risk screening-2002) and functional status (SARC-F, clinical frailty scale [CFS], Katz activities of daily living [ADL] and Lawton Instrumental ADL). Results: Ninety patients were recruited. A total of 86, 53, 24 and 10 US measures were analyzed, which were performed at a median of 1, 7, 14 and 22 days from ICU admission, respectively. QMLT, RFCSA and PA reduced significantly over time. The overall trend of change of FL was not significant. The only independent predictor of 60-day mortality was the change of QMLT from baseline to day 7 (adjusted odds ratio 0.95 for every 1% less QMLT loss, 95% confidence interval 0.91-0.99; p = 0.02). Baseline measures of high nutrition risk (modified nutrition risk in critically ill ≥5), sarcopenia (SARC-F ≥4) and frailty (CFS ≥5) were associated with lower baseline QMLT, RFCSA and PA and higher 60-day mortality. Conclusions: Every 1% loss of QMLT over the first week of critical illness was associated with 5% higher odds of 60-day mortality. SARC-F, CFS and mNUTRIC are associated with quadriceps muscle status and 60-day mortality and may serve as a potential simple and indirect measures of premorbid muscle status at ICU admission