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Beta-glucans, naturally present in foods like wheat, mushrooms, and yeast, have shown potential in reversing immunosuppression. However, the existing evidence solely relies on ex vivo studies assessing direct effects of β-glucans on macrophages. To investigate whether such effects also occur after their oral administration, this study first systematically examined the immunosuppressive effects of LPS in mice. Subsequently, we assessed the ability of yeast-derived whole β-glucan particles (yWGP), administered through the diet, to counteract LPS-induced immunological tolerance. Immunosuppression following intraperitoneal administration of 20, 200, or 2000 μg kg -1 LPS was demonstrated by reduced TNF-α and IL-6 release upon ex vivo LPS stimulation of immune cells harvested from the peritoneal fluid, spleen, and bone marrow. Immunosuppression in blood was detected only after 200 and 2000 μg kg -1 LPS. LPS tolerance extended to heterologous stimuli (PAM3Cys, heat-killed Pseudomonas aeruginosa ), indicating cross-tolerance. Due to animal discomfort at 2000 μg kg -1 LPS, as evidenced by a significantly enhanced clinical severity score, a dose of 200 μg kg -1 LPS was selected for the follow-up trial. In this experiment, mice fed a yWGP-supplemented diet for two weeks prior to LPS administration showed effective reversal of LPS tolerance, reflected by restored TNF-α levels in peritoneal cells but not in other monocyte- and macrophage-containing cell populations. Together, these studies demonstrate that peritoneal administration of 200 μg kg -1 LPS induced ex vivo LPS tolerance in all immunological organs studied, without significantly compromising animal welfare. The selective efficacy of dietary β-glucans to counteract immunosuppression, which is often observed in vulnerable and immunocompromised patient populations, warrants further clinical evaluation.

Edible insects have been proposed as a novel and sustainable source of protein and other essential nutrients for human consumption but nutrient absorption efficiency is still uncertain. We investigated zinc absorption from house crickets (Acheta domesticus) in a single-center and single-blinded cross-over study with children aged 24-36 months old in Kenya from September-November 2021. For this, children were randomized to consume two different experimental meals labeled with stable isotopes of zinc (Zn) at two different days, separated by a wash-out period of one month. Primary endpoints were the differences in amount of absorbed zinc (AZ) from maize-based meals enriched with intrinsically 67 Zn-labeled house crickets (2.61 mg Zn, n = 28) in comparison with meals enriched with 68 Zn (low-enriched: 0.90 mg Zn, n = 29); high-enriched: 3.24 mg Zn, n = 28) or with intrinsically 67 Zn-labeled low-chitin cricket flour (2.51 mg Zn, n = 25), whereas the secondary endpoints were the differences in fractional zinc absorption. We found that AZ from meals with whole crickets (geometric mean: 0.36 mg; 95%CI: 0.30, 0.43) was 2.6 times higher than from low-enriched maize meals (0.14 mg; 0.11, 0.16; P < 0.001), while it was not different from low-chitin cricket flour meals. Absorbed zinc from both cricket meals was higher than that from high-enriched meals. No severe adverse side events were reported. We conclude that edible house crickets are a good source of well-absorbable zinc, and their increased consumption could contribute to the alleviation of zinc deficiency. This trial was registered at the Pan African Clinical Trials Registry as PACTR202104533831364., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The effect of fermented foods on healthy human gut microbiota structure and function, particularly its seasonal preference and frequent long-term consumption, has been largely uncharacterised. Here, we assess the gut microbiota and metabolite composition of 78 healthy Indian agrarian individuals who differ in the intake of fermented milk and soybean products by seasonal sampling during hot-humid summer, autumn and dry winter. Here we show that, seasonal shifts between the Prevotella- and Bifidobacterium/Ruminococcus-driven community types, or ecological states, and associated fatty acid derivatives, with a bimodal change in Bacteroidota community structure during summer, particularly in fermented milk consumers. Our results associate long-term fermented food consumption with reduced gut microbiota diversity and bacterial load. We identify taxonomic groups that drive the seasonal fluctuation and associated shifts between the two ecological states in gut microbiota. This understanding may pave the way towards developing strategies to sustain a healthy and resilient gut microbiota through dietary interventions., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objective: Given that Parkinson's disease is a progressive disorder, with symptoms that worsen over time, our goal is to enhance the diagnosis of Parkinson's disease by utilizing machine learning techniques and microbiome analysis. The primary objective is to identify specific microbiome signatures that can reproducibly differentiate patients with Parkinson's disease from healthy controls., Methods: We used four Parkinson-related datasets from the NCBI repository, focusing on stool samples. Then, we applied a DADA2-based script for amplicon sequence processing and the Recursive Ensemble Feature Selection (REF) algorithm for biomarker discovery. The discovery dataset was PRJEB14674, while PRJNA742875, PRJEB27564, and PRJNA594156 served as testing datasets. The Extra Trees classifier was used to validate the selected features., Results: The Recursive Ensemble Feature Selection algorithm identified 84 features (Amplicon Sequence Variants) from the discovery dataset, achieving an accuracy of over 80%. The Extra Trees classifier demonstrated good diagnostic accuracy with an area under the receiver operating characteristic curve of 0.74. In the testing phase, the classifier achieved areas under the receiver operating characteristic curves of 0.64, 0.71, and 0.62 for the respective datasets, indicating sufficient to good diagnostic accuracy. The study identified several bacterial taxa associated with Parkinson's disease, such as Lactobacillus, Bifidobacterium, and Roseburia, which were increased in patients with the disease., Conclusion: This study successfully identified microbiome signatures that can differentiate patients with Parkinson's disease from healthy controls across different datasets. These findings highlight the potential of integrating machine learning and microbiome analysis for the diagnosis of Parkinson's disease. However, further research is needed to validate these microbiome signatures and to explore their therapeutic implications in developing targeted treatments and diagnostics for Parkinson's disease., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Exposure to pollutants like environmental cigarette smoke (CS) poses a major global health risk, affecting individuals from an early age. Therefore, this study explores how postnatal synbiotic supplementation affects allergic asthma symptoms in house-dust-mite (HDM)- challenged offspring maternally exposed to CS. In HDM-allergic offspring of CS-exposed dams, lung resistance was elevated, but synbiotic supplementation effectively reduced this resistance. Elevated eosinophil BALF counts following HDM challenge were intensified in pups maternally exposed to CS. Similarly, Th2 cell activation and serum IgE and IgG1 levels were more pronounced in HDM-allergic offspring of CS-exposed mothers. Synbiotics reduced eosinophil numbers and serum IgE and IgG1, and tended to decrease Th2 cell infiltration and activation. Synbiotics promoted beneficial gut bacteria like Bifidobacterium and Akkermansia. In conclusion, early-life synbiotic intervention mitigated allergic asthma associated with maternal air pollution exposure, highlighting the potential of synbiotics for clinical evaluation as a strategy to prevent allergy development in offspring., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Johan Garssen reports financial support was provided by Danone Nutricia Research. Jeroen van Bergenhenegouwen reports a relationship with Danone Nutricia Research that includes: employment. Johan Garssen reports a relationship with Danone Nutricia Research that includes: employment. Saskia Braber reports a relationship with Danone Nutricia Research that includes: employment. The remaining authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Rationale: Disease course in sarcoidosis is highly variable. Bronchoalveolar lavage fluid and mediastinal lymph nodes show accumulation of activated T cells with a T-helper (Th)17.1 signature, which correlates with non-resolving sarcoidosis. We hypothesize that the peripheral blood (PB) T cell phenotype may correlate with outcome., Objectives: To compare frequencies, phenotypes and function of circulating T cell populations in sarcoidosis patients with healthy controls (HCs) and correlate these parameters with outcome., Methods: We used multi-color flow cytometry to quantify activation marker expression on PB T cell subsets in treatment-naïve patients and HCs. The disease course was determined after 2-year follow-up. Cytokine production was measured after T cell stimulation in vitro., Measurements and Main Results: We observed significant differences between patients and HCs in several T cell populations, including CD8 + and CD4 + T cells, Th1/Th17 subsets, CD4 + T memory stem cells, regulatory T cells (Tregs) and γδ T cells. Decreased frequencies of CD4 + T cells and increased frequencies of Tregs and CD8 + γδ T cells correlated with worse outcome. Naïve CD4 + T cells displayed an activated phenotype with increased CD25 expression in patients with active chronic disease at 2-year follow-up. A distinctive Treg phenotype with increased expression of CD25, CTLA4, CD69, PD-1 and CD95 correlated with chronic sarcoidosis. Upon stimulation, both naïve and memory T cells displayed a different cytokine profile in sarcoidosis compared to HCs., Conclusions: Circulating T cell subpopulations of sarcoidosis patients display phenotypic abnormalities that correlate with disease outcome, supporting a critical role of aberrant T cell activation in sarcoidosis pathogenesis., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Length measurement in young children younger than 18 months is important for monitoring growth and development. Accurate length measurement requires proper equipment, standardized methods, and trained personnel. In addition, length measurement requires young children's cooperation, making it particularly challenging during infancy and toddlerhood., Objective: This study aimed to develop a length artificial intelligence (LAI) algorithm to aid users in determining recumbent length conveniently from smartphone images and explore its performance and suitability for personal and clinical use., Methods: This proof-of-concept study in healthy children (aged 0-18 months) was performed at KK Women's and Children's Hospital, Singapore, from November 2021 to March 2022. Smartphone images were taken by parents and investigators. Standardized length-board measurements were taken by trained investigators. Performance was evaluated by comparing the tool's image-based length estimations with length-board measurements (bias [mean error, mean difference between measured and predicted length]; absolute error [magnitude of error]). Prediction performance was evaluated on an individual-image basis and participant-averaged basis. User experience was collected through questionnaires., Results: A total of 215 participants (median age 4.4, IQR 1.9-9.7 months) were included. The tool produced a length prediction for 99.4% (2211/2224) of photos analyzed. The mean absolute error was 2.47 cm for individual image predictions and 1.77 cm for participant-averaged predictions. Investigators and parents reported no difficulties in capturing the required photos for most participants (182/215, 84.7% participants and 144/200, 72% participants, respectively)., Conclusions: The LAI algorithm is an accessible and novel way of estimating children's length from smartphone images without the need for specialized equipment or trained personnel. The LAI algorithm's current performance and ease of use suggest its potential for use by parents or caregivers with an accuracy approaching what is typically achieved in general clinics or community health settings. The results show that the algorithm is acceptable for use in a personal setting, serving as a proof of concept for use in clinical settings., Trial Registration: ClinicalTrials.gov NCT05079776; https://clinicaltrials.gov/ct2/show/NCT05079776., (©Mei Chien Chua, Matthew Hadimaja, Jill Wong, Sankha Subhra Mukherjee, Agathe Foussat, Daniel Chan, Umesh Nandal, Fabian Yap. Originally published in JMIR Pediatrics and Parenting (https://pediatrics.jmir.org), 22.11.2024.)

Food contact materials should not release their constituent substances into food at levels harmful to human health nor change the food composition, taste, or odor unacceptably. The historical evolution of food packaging shows that the use of plastics has increased dramatically, because of its convenience, lightweight, and cost effectiveness, but carries a significant environmental impact. Influenced by trends such as growing awareness of the environmental footprint and stricter safety requirements, conventional packaging is now progressively evolving toward new alternatives. All stakeholders in the agrifood system are involved in the journey to transform food packaging to more sustainable alternatives, while maintaining the important functionalities of suitable food packaging. The current most promising food packaging alternatives are presented in this review with their benefits, limitations, and associated potential safety hazards, with a focus on chemical hazards. Although some potential hazards are common to conventional packaging, others are specific to the new alternatives. Identification of potential chemical hazards associated with these new packaging alternatives is important to anticipate any risks posed to consumer safety. With much diversity in packaging types and rules aimed at ensuring safety drastically varying between jurisdictions, it is not always easy to determine the best way to assess the safety of food packaging. International guidance on principles for safe food packaging could help drive global harmonization and would play a crucial role in ensuring a consistent and science-based framework for the safety and compliance of new and emerging food packaging., (© 2024 Food and Agriculture Organization of the United Nations.)

Currently available guidelines on the daily formula milk requirements of infants are based on the needs of infants with their growth pattern following the 50th percentile of the weight-for-age growth curve. Hence, current recommendations may not thoroughly detail the needs of infants across the broad spectrum of body weight percentiles. This study aimed to provide stratified recommendations for daily formula milk intake of fully formula-fed infants, across different weight-for-age categories from 0 to 4 months. At first, theoretical age- and gender-specific weight ranges were constructed for infants across five pre-defined weight-for-length percentile categories of the WHO growth standard. Thereafter, total daily energy requirements for each category were calculated and converted to daily formula milk needs. Subsequently, these stratified age- and weight-formula milk recommendations were compared to actual daily and relative formula milk of infants in these categories, retrieved from pooled individual infant formula milk intake data derived from 13 clinical intervention trials. A fitted regression model was used to evaluate differences in volume intakes across body weight categories as well as between theoretically derived and actual intake values. Median daily formula milk volume intake (ml/day) of infants differed significantly across the increasing weight-for-age categories at each time point, with significant differences between small and large infants. Interestingly, the relative daily formula milk volume intake (ml/kg/day) was higher for smaller infants compared to larger infants. The mean daily and relative formula milk intakes demonstrated the same pattern based on theoretical calculations as well as for the actual formula milk intake values retrieved from 13 pooled clinical intervention trials., Conclusions: Based on theoretical calculations and actual formula intake data, we conclude that larger infants require a significantly higher daily formula milk intake than smaller infants, and we postulate that infants could benefit from more tailored formula milk intake recommendations., What Is Known: • Adequate energy intake during the infancy period is crucial to support optimal growth and organ development, with the potential for long-lasting health effects. • Current available guidelines on the daily formula milk requirements of infants are based on the needs of infants with their growth pattern following the 50th percentile of the weight-for-age growth curve., What Is New: • Based on using both theoretical calculations and actual formula intake data, larger infants require a significantly higher daily formula milk intake than smaller infants. • Exclusive formula-fed infants could benefit from more tailored formula milk intake recommendations, in early infancy., (© 2024. The Author(s).)

Degenerative joint disease osteoarthritis (OA) is characterized by the degeneration of cartilage, synovial inflammation and low-grade systemic inflammation in association with microbial dysbiosis and intestinal barrier defects. Butyrate is known for its anti-inflammatory and barrier protective effects and might benefit OA patients. In a double-blind placebo-controlled randomized trial, the effects of four to five weeks of oral treatment with sustained-release (SR) butyrate tablets (600 mg/day) on systemic inflammation and immune function were studied in hand OA patients. Serum markers for systemic inflammation and lipopolysaccharide (LPS) leakage were measured and ex vivo stimulation of whole blood or peripheral blood mononuclear cells (PBMCs) was performed at baseline and after treatment. Butyrate treatment did not affect the serum markers nor the cytokine release of ex vivo LPS-stimulated whole blood or PBMCs nor the phenotype of restimulated monocytes. By contrast, butyrate treatment reduced the percentage of activated T helper (Th) cells and the Th17/Treg ratio in αCD3/CD28-activated PBMCs, though cytokine release upon stimulation remained unaffected. Nevertheless, the percentage of CD4+IL9+ cells was reduced by butyrate as compared to the placebo. In both groups, the frequency of Th1, Treg, Th17, activated Th17, CD4+IFNγ+ and CD4+TNFα+ cells was reduced. This study shows a proof of principle of some immunomodulatory effects using a SR butyrate treatment in hand OA patients. The inflammatory phenotype of Th cells was reduced, as indicated by a reduced percentage of Th9 cells, activated Th cells and improved Th17/Treg balance in ex vivo αCD3/CD28-activated PBMCs. Future studies are warranted to further optimize the butyrate dose regime to ameliorate inflammation in OA patients.

Context: Combining or supplementing breastfeeding with formula feeding, also called mixed milk feeding (MMF), is a common infant feeding practice. However, there is no well-established MMF evidence-base for informing and guiding parents. A better understanding of the reasons why mothers practice MMF may facilitate identification of efficient strategies for supporting exclusive breastfeeding, and/or opportunities to prolong breastfeeding, at least partially., Objective: An updated systematic literature review was undertaken with the primary aim of gaining a deeper understanding of the reasons why mothers choose MMF., Data Sources: Six databases were searched for relevant articles published in English from January 2012 to January 2022., Data Extraction: Two reviewers independently performed the screenings and data extraction, and any differences were resolved by a third reviewer. Data from 138 articles were included, 90 of which contained data on MMF reasons/drivers, and 60 contained data on infant age and/or maternal demographic factors associated with MMF., Data Analysis: A total of 13 different unique MMF drivers/reasons were identified and categorized according to whether the drivers/reasons related to perceived choice, necessity, or pressure. Risk of bias was evaluated using the Quality Assessment Tool of Diverse Studies and the JBI Systematic Reviews tool. Several different terms were used to describe and classify MMF across the studies. The most commonly reported reasons for MMF were related to a perception of necessity (39% of drivers, eg, concerns about infant's hunger/perceived breast milk insufficiency or breastfeeding difficulties), followed by drivers associated with perceived choice (34%; eg, having more flexibility) and perceived pressure (25%; eg, returning to work or healthcare professionals' advice). This was particularly true for infants aged 3 months or younger., Conclusion: The key global drivers for MMF and their distribution across infant age and regions were identified and described, providing opportunities for the provision of optimal breastfeeding support. A unified definition of MMF is needed in order to enable more comparable and standardized research., Systematic Review Registration: PROSPERO registration no. CRD42022304253., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Life Sciences Institute.)

Background: Cachexia, a syndrome with high prevalence in non-small cell lung cancer patients, impairs quality of life and reduces tolerance and responsiveness to cancer therapy resulting in decreased survival. Optimal nutritional care is pivotal in the treatment of cachexia and a recommended cornerstone of multimodal therapy. Here, we investigated the therapeutic effect of an intervention diet consisting of a specific combination of high protein, leucine, fish oil, vitamin D, galacto-oligosaccharides, and fructo-oligosaccharides on the development and progression of cachexia in an orthotopic lung cancer mouse model., Methods: Eleven-week-old male 129S2/Sv mice were orthotopically implanted with 344P lung epithelial tumour cells or vehicle (control). Seven days post-implantation tumour-bearing (TB) mice were allocated to either intervention- or isocaloric control diet. Cachexia was defined as 5 days of consecutive body weight loss, after which mice were euthanized for tissue analyses., Results: TB mice developed cachexia accompanied by significant loss of skeletal muscle mass and epididymal fat mass compared with sham operated mice. The cachectic endpoint was significantly delayed (46.0 ± 15.2 vs. 34.7 ± 11.4 days), and the amount (-1.57 ± 0.62 vs. -2.13 ± 0.57 g) and progression (-0.26 ± 0.14 vs. -0.39 ± 0.11 g/day) of body weight loss were significantly reduced by the intervention compared with control diet. Moreover, systemic inflammation (pentraxin-2 plasma levels) and alterations in molecular markers for proteolysis and protein synthesis, indicative of muscle atrophy signalling in TB-mice, were suppressed in skeletal muscle by the intervention diet., Conclusions: Together, these data demonstrate the potential of this multinutrient intervention, targeting multiple components of cachexia, as integral part of lung cancer management., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Objective: To determine the prevalence and co-occurrence of common geriatric syndromes in geriatric rehabilitation inpatients., Design: Restoring Health of Acutely Unwell Adults (RESORT) and Enhancing Muscle Power in Geriatric Rehabilitation (EMPOWER-GR) are observational, longitudinal cohorts., Setting: Geriatric rehabilitation., Participants: Geriatric rehabilitation inpatients (N=1890 and N=200)., Interventions: Not applicable., Main Outcome Measures: Geriatric syndromes included polypharmacy, multimorbidity (Cumulative Illness Rating Scale), cognitive impairment, depression (Hospital Anxiety and Depression Scale/Geriatric Depression Scale), malnutrition (Global Leadership Initiative on Malnutrition), functional limitation (Katz index), falls, physical frailty (Fried), and sarcopenia (European Working Group on Sarcopenia in Older People 2)., Results: Inpatients in RESORT (R) (N=1890, 56% females) had a median age of 83.4 years (interquartile range [IQR], 77.6-88.4) and in EMPOWER-GR (E) (N=200, 57% females) of 79.8 years (IQR, 75.0-85.9). Polypharmacy (R, 82.2%; E, 84.0%), multimorbidity (R, 90.4%; E, 85.5%), functional limitation (R, 96.0%; E, 76.5%), and frailty (R, 91.8%; E, 92.2%) were most prevalent. Most inpatients had ≥5 geriatric syndromes at admission in both cohorts (R, 70.0%; E, 72.4%); few inpatients had only 1 (R, 0.4%; E, 1.5%) or no geriatric syndrome (R, 0.2%; E, 0.0%). Geriatric syndromes did not occur in isolation (without other syndromes), except for multimorbidity (R, 1%; E, 5%), functional limitation (R, 3%; E, 2%), falls (R, 0%; E, 4%), and frailty (R, 2%; E, 5%), which occurred in isolation in some inpatients; sarcopenia did not., Conclusions: Geriatric syndromes are highly prevalent at admission to geriatric rehabilitation, with a median of 5 co-occurring syndromes. Implications for diagnosis and intervention potential should be further addressed., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Limited evidence exists on the preferred feeding method when breastfeeding is not possible in late and moderate preterm (LMPT) infants. This RCT evaluates growth, safety, and tolerance of a concept infant formula (IF) with large, milk phospholipid-coated lipid droplets enriched in dairy lipids in LMPT infants with primary objective to demonstrate non-inferiority of daily weight gain from randomization to 3 months corrected age compared to a standard IF., Methods: LMPT infants were randomized before or around term equivalent age to either the concept (n = 21) or standard IF (n = 20). Forty-one breastfed (BF) infants served as reference., Results: Due to unintended low recruitment, non-inferiority in daily weight gain could not be demonstrated for the Concept compared to the Control group, but was compared to the BF group. Other outcomes were similar between the formula groups, except for an apparent larger head circumference gain in the Concept group. No apparent differences in growth and body composition outcomes were observed between the Concept and BF reference groups., Conclusion: This small-scale study suggests the concept IF is a safe alternative for parents who choose IF to feed their LMPT infant. Larger trials are needed to better determine impacts on head growth or body composition., Impact: In a small group of late and moderate preterm infants, growth from randomization until 3 months corrected age of infants fed with a concept infant formula with large, milk phospholipid-coated lipid droplets was not -significantly different from infants fed a standard infant formula. Infants in the Concept group had non-significant larger gain in head circumference compared to the Control group; larger trials are needed to confirm this finding. Both formulas were well-tolerated, with no differences in adverse events. The concept formula is potentially a safe alternative for parents of moderate to late preterm infants who choose to use formula milk., (© 2024. The Author(s).)

Models predicting lipid oxidation in oil-in-water (O/W) emulsions are a requirement for developing effective antioxidant solutions. Existing models do, however, not include explicit equations that account for composition and structural features of O/W emulsions. To bridge this gap, a mechanistic kinetic model for lipid oxidation in emulsions is presented, describing the emulsion as a one-dimensional three phase (headspace, water, and oil) system. Variation in oil droplet sizes, overall surface area of oil/water interface, oxidation of emulsifiers, and the presence of catalytic transition metals were accounted for. For adequate predictions, the overall surface area of oil/water interface needs to be determined from the droplet size distribution obtained by dynamic and static light scattering (DLS, SLS). The kinetic model predicted well the formation of oxidation products in both mono- and polydisperse emulsions, with and without presence of catalytic transition metals., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Arend Dubbelboer and John P.M. Van Duynhoven are employed by companies that manufacture and market oil based food products., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Streptococcus thermophilus is a bacterium widely used in the production of yogurts and cheeses, where it efficiently ferments lactose, the saccharide naturally present in milk. It is also employed as a starter in dairy- or plant-based fermented foods that contain saccharides other than lactose (e.g., sucrose, glucose). However, little is known about how saccharide use is regulated, in particular when saccharides are mixed. Here, we determine the effect of the 5 sugars that S. thermophilus is able to use, at different concentration and when they are mixed on the promoter activities of the C-metabolism genes. Using a transcriptional fusion approach, we discovered that lactose and glucose modulated the activity of the lacS and scrA promoters in a concentration-dependent manner. When mixed with lactose, glucose also repressed the two promoter activities; when mixed with sucrose, lactose still repressed scrA promoter activity. We determined that catabolite control protein A (CcpA) played a key role in these dynamics. We also showed that promoter activity was linked with glycolytic flux, which varied depending on saccharide type and concentration. Overall, this study identified key mechanisms in carbohydrate metabolism - autoregulation and partial hierarchical control - and demonstrated that they are partly mediated by CcpA., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Autism spectrum disorder (ASD) is a cluster of neurodevelopmental disorders characterized by deficits in communication and behavior. Increasing evidence suggests that the microbiota-gut-brain axis and the likely related immune imbalance may play a role in the development of this disorder. Gastrointestinal deficits and gut microbiota dysfunction have been linked to the development or severity of autistic behavior. Therefore, treatments that focus on specific diets may improve gastrointestinal function and aberrant behavior in individuals with ASD. In this study, we investigated whether a diet containing specific prebiotic fibers, namely, 3% galacto-oligosaccharide/fructo-oligosaccharide (GOS/FOS; 9:1), can mitigate the adverse effects of in utero exposure to valproic acid (VPA) in mice. Pregnant BALB/cByJ dams were injected with VPA (600 mg/kg, sc.) or phosphate-buffered saline (PBS) on gestational day 11 (G11). Male offspring were divided into four groups: (1) in utero PBS-exposed with a control diet, (2) in utero PBS-exposed with GOS/FOS diet, (3) in utero VPA-exposed with a control diet, and (4) in utero VPA-exposed with GOS/FOS diet. Dietary intervention started from birth and continued throughout the duration of the experiment. We showed that the prebiotic diet normalized VPA-induced alterations in male offspring, including restoration of key microbial taxa, intestinal permeability, peripheral immune homeostasis, reduction of neuroinflammation in the cerebellum, and impairments in social behavior and cognition in mice. Overall, our research provides valuable insights into the gut-brain axis involvement in ASD development. In addition, dietary interventions might correct the disbalance in gut microbiota and immune responses and, ultimately, might improve detrimental behavioral outcomes in ASD., (© 2024. The Author(s).)

The growing world population, changing dietary habits, and increasing pressure on agricultural resources are drivers for the development of novel foods (including new protein sources as well as existing protein sources that are produced or used in an alternative way or in a different concentration). These changes, coupled with consumer inclination to adopt new dietary trends, may heighten the intake of unfamiliar proteins, or escalate consumption of specific ones, potentially amplifying the prevalence of known and undiscovered food allergies. Assessing the allergenicity of novel or modified protein-based foods encounters several challenges, including uncertainty surrounding acceptable risks and assessment criteria for determining safety. Moreover, the available methodological tools for gathering supportive data exhibit significant gaps. This paper synthesises these challenges, addressing the varied interpretations of "safe" across jurisdictions and societal attitudes towards allergenic risk. It proposes a comprehensive two-part framework for allergenicity assessment: the first part emphasises systematic consideration of knowledge and data requirements, while the second part proposes the application of a generic assessment approach, integrating a Threshold of Allergological Concern. This combined framework highlights areas that require attention to bridge knowledge and data gaps, and it delineates research priorities for its development and implementation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rene Crevel reports financial support and travel were provided by International Life Sciences Institute Europe (ILSI Europe). Geert Houben reports financial support was provided by ILSI Europe. Rene Crevel reports a relationship with AllPreT Horizon Europe Marie Curie Doctoral Training Network Project that includes: board membership and travel reimbursement. Geert Houben reports a relationship with Netherlands Organization for Applied Scientific Research that includes: employment. Ross Yarham reports a relationship with InBio that includes: employment. Katrine Lindholm Bogh reports a relationship with Technical University of Denmark National Food Institute that includes: employment. Neil Buck reports a relationship with General Mills Inc that includes: employment. Melina Galano reports a relationship with dsm-firmenich that includes: employment. Kitty Verhoeckx reports a relationship with University Medical Center Utrecht that includes: employment. I have received fees through René Crevel Consulting Ltd for risk assessment of the proposed use of various proteins by Meatable B.V. , Upfield B.V. and Mozza Inc. - R.C. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Life Sciences Institute Europe. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Pulmonary neutrophilia is a hallmark of numerous airway diseases including Chronic Obstructive Pulmonary Disease (COPD), Neutrophilic asthma, Acute Lung Injury (ALI), Acute Respiratory Distress Syndrome (ARDS) and COVID-19. The aim of the current study was to investigate the effect of dietary interventions on lung health in context of pulmonary neutrophilia., Methods: Male BALB/cByJ mice received 7 intra-nasal doses of either a vehicle or lipopolysaccharides (LPS). To study the effect of nutritional interventions they received 16 intra-gastric doses of either a vehicle (PBS) or the following supplements (1) probiotic Bifidobacterium breve ( B. breve ) M16-V; (2) a prebiotic fiber mixture of short-chain galacto-oligosaccharides, long-chain fructo-oligosaccharides, and low-viscosity pectin in a 9:1:2 ratio (scGOS/lcFOS/lvPectin); and (3) A synbiotic combination B. breve M16-V and scGOS/lcFOS/lvPectin. Parameters for lung health included lung function, lung morphology and lung inflammation. Parameters for systemic immunomodulation included levels of fecal short chain fatty acids and regulatory T cells., Results: The synbiotic supplement protected against the LPS induced decline in lung function (35% improved lung resistance at baseline p  = 0.0002 and 25% at peak challenge, p  = 0.0002), provided a significant relief from pulmonary neutrophilia (40.7% less neutrophils, p  < 0.01) and improved the pulmonary neutrophil-to-lymphocyte ratio (NLR) by 55.3% ( p  = 0.0033). Supplements did not impact lung morphology in this specific experiment. LPS applied to the upper airways induced less fecal SCFAs production compared to mice that received PBS. The production of acetic acid between day -5 and day 16 was increased in all unchallenged mice (PBS-PBS p  = 0.0003; PBS-Pro p  < 0.0001; PBS-Pre, p  = 0.0045; PBS-Syn, p  = 0.0005) which upon LPS challenge was only observed in mice that received the synbiotic mixture of B. breve M16-V and GOS:FOS:lvPectin ( p  = 0.0003). A moderate correlation was found for butyric acid and lung function parameters and a weak correlation was found between acetic acid, butyric acid and propionic acid concentrations and NLR., Conclusion: This study suggests bidirectional gut lung cross-talk in a mouse model for pulmonary neutrophilia. Neutrophilic lung inflammation coexisted with attenuated levels of fecal SCFA. The beneficial effects of the synbiotic mixture of B. breve M16-V and GOS:FOS:lvPectin on lung health associated with enhanced levels of SCFAs., Competing Interests: JB and JG are both in part affiliated with Danone Nutricia Research BV, a company having commercial interest in dietary products. GB was in part employed by Impact Station. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bezemer, Diks, Mortaz, van Ark, van Bergenhenegouwen, Kraneveld, Folkerts and Garssen.)

Background: 5-Fluorouracil (5-FU) is used as an antineoplastic agent in distinct cancer types. Increasing evidence suggests that the gut microbiota might modulate 5-FU efficacy and toxicity, potentially affecting the patient's prognosis. The current experimental study investigated 5-FU-induced microbiota alterations, as well as the potential of prebiotic fibre mixtures (M1-M4) to counteract these shifts., Methods: A pooled microbial consortium was derived from ten healthy donors, inoculated in an in vitro model of the colon, and treated with 5-FU, with or without prebiotic fibre mixtures for 72 h. Four different prebiotic fibre mixtures were tested: M1 containing short-chain galacto-oligosaccharides (sc GOS), long-chain fructo-oligosaccharides (lcFOS), and low viscosity pectin (lvPect), M2 consisting of arabinoxylan, beta-glucan, pectin, and resistant starch, M3 which was a mixture of scGOS and lcFOS, and M4 containing arabinoxylan, beta-glucan, pectin, resistant starch, and inulin., Results: We identified 5-FU-induced changes in gut microbiota composition, but not in microbial diversity. Administration of prebiotic fibre mixtures during 5-FU influenced gut microbiota composition and taxa abundance. Amongst others, prebiotic fibre mixtures successfully stimulated potentially beneficial bacteria (Bifidobacterium, Lactobacillus, Anaerostipes, Weissella, Olsenella, Senegalimassilia) and suppressed the growth of potentially pathogenic bacteria (Klebsiella, Enterobacter) in the presence of 5-FU. The short-chain fatty acid (SCFA) acetate increased slightly during 5-FU, but even more during 5-FU with prebiotic fibre mixtures, while propionate was lower due to 5-FU with or without prebiotic fibre mixtures, compared to control. The SCFA butyrate and valerate did not show differences among all conditions. The branched-chain fatty acids (BCFA) iso-butyrate and iso-valerate were higher in 5-FU, but lower in 5-FU + prebiotics, compared to control., Conclusions: These data suggest that prebiotic fibre mixtures represent a promising strategy to modulate 5-FU-induced microbial dysbiosis towards a more favourable microbiota, thereby possibly improving 5-FU efficacy and reducing toxicity, which should be evaluated further in clinical studies., (© 2024. The Author(s).)

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., Competing Interests: JG is part time employee/scientific advisor of Danone Nutricia Research. RB-S is employee of Danone Nutricia Research, and KK was also at time of the experiment. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Sáez-Fuertes, Kapravelou, Grases-Pintó, Massot-Cladera, Bernabeu, Knipping, Garssen, Bourdet-Sicard, Castell, Rodríguez-Lagunas, Collado and Pérez-Cano.)

Mustard seeds belong to the food category of mandatory labelling due to the severe reactions they can trigger in allergic patients. However, the mechanisms underlying allergic sensitization to mustard seeds are poorly understood. The aim of this work is to study type 2 immune activation induced by the mustard seed major allergen Sin a1 via the intestinal mucosa, employing an in vitro model mimicking allergen exposure via the intestinal epithelial cells (IECs). Sin a1 was isolated from the total protein extract and exposed to IEC, monocyte derived dendritic cells (DCs) or IEC/DC co-cultures. A system of consecutive co-cultures was employed to study the generic capacity of Sin a1 to induce type 2 activation leading to sensitization: IEC/DC, DC/T-cell, T/B-cell and stem cell derived mast cells (MCs) derived from healthy donors. Immune profiles were determined by ELISA and flow cytometry. Sin a1 activated IEC and induced type-2 cytokine secretion in IEC/DC co-culture or DC alone (IL-15, IL-25 and TSLP), and primed DC induced type 2 T-cell skewing. IgG secretion in the T-cell/B-cell phase was enhanced in the presence of Sin a1 in the first stages of the co-culture. Anti-IgE did not induce degranulation but promoted IL-13 and IL-4 release by MC primed with the supernatant from B-cells co-cultured with Sin a1-IEC/DC or -DC primed T-cells. Sin a1 enhanced the release of type-2 inflammatory mediators by epithelial and dendritic cells; the latter instructed generic type-2 responses in T-cells that resulted in B-cell activation, and finally MC activation upon anti-IgE exposure. This indicates that via activation of IEC and/or DC, mustard seed allergen Sin a1 is capable of driving type 2 immunity which may lead to allergic sensitization.

Background: Preterm born infants are at risk for brain injury and subsequent developmental delay. Treatment options are limited, but optimizing postnatal nutrition may improve brain- and neurodevelopment in these infants. In pre-clinical animal models, combined supplementation of docosahexaenoic acid (DHA), choline, and uridine-5-monophosphate (UMP) have shown to support neuronal membrane formation. In two randomized controlled pilot trials, supplementation with the investigational product was associated with clinically meaningful improvements in cognitive, attention, and language scores. The present study aims to assess the effect of a similar nutritional intervention on brain development and subsequent neurodevelopmental outcome in infants born very and extremely preterm., Methods: This is a randomized, placebo-controlled, double-blinded, parallel-group, multi-center trial. A total of 130 infants, born at less than 30 weeks of gestation, will be randomized to receive a test or control product between term-equivalent age and 12 months corrected age (CA). The test product is a nutrient blend containing DHA, choline, and UMP amongst others. The control product contains only fractions of the active components. Both products are isocaloric powder supplements which can be added to milk and solid feeds. The primary outcome parameter is white matter integrity at three months CA, assessed using diffusion-tensor imaging (DTI) on MRI scanning. Secondary outcome parameters include volumetric brain development, cortical thickness, cortical folding, the metabolic and biochemical status of the brain, and product safety. Additionally, language, cognitive, motor, and behavioral development will be assessed at 12 and 24 months CA, using the Bayley Scales of Infant Development III and digital questionnaires (Dutch version of the Communicative Development Inventories (N-CDI), Ages and Stages Questionnaire 4 (ASQ-4), and Parent Report of Children's Abilities - Revised (PARCA-R))., Discussion: The investigated nutritional intervention is hypothesized to promote brain development and subsequent neurodevelopmental outcome in preterm born infants who have an inherent risk of developmental delay. Moreover, this innovative study may give rise to new treatment possibilities and improvements in routine clinical care., Trial Registration: WHO International Clinical Trials Registry: NL-OMON56181 (registration assigned October 28, 2021)., (© 2024. The Author(s).)

Background: Chronic low-grade inflammatory profile (CLIP) is one of the pathways involved in type 2 diabetes (T2D). Currently, there is limited evidence for ameliorating effects of combined lifestyle interventions on CLIP in type 2 diabetes. We investigated whether a 13-week combined lifestyle intervention, using hypocaloric diet and resistance exercise plus high-intensity interval training with or without consumption of a protein drink, affected CLIP in older adults with T2D., Methods: In this post-hoc analysis of the PROBE study 114 adults (≥55 years) with obesity and type 2 (pre-)diabetes had measurements of C-reactive protein (CRP), pro-inflammatory cytokines interleukin (IL)-6, tumor-necrosis-factor (TNF)-α, and monocyte chemoattractant protein (MCP)-1, anti-inflammatory cytokines IL-10, IL-1 receptor antagonist (RA), and soluble tumor-necrosis-factor receptor (sTNFR)1, adipokines leptin and adiponectin, and glycation biomarkers carboxymethyl-lysine (CML) and soluble receptor for advanced glycation end products (sRAGE) from fasting blood samples. A linear mixed model was used to evaluate change in inflammatory biomarkers after lifestyle intervention and effect of the protein drink. Linear regression analysis was performed with parameters of body composition (by dual-energy X-ray absorptiometry) and parameters of insulin resistance (by oral glucose tolerance test)., Results: There were no significant differences in CLIP responses between the protein and the control groups. For all participants combined, IL-1RA, leptin and adiponectin decreased after 13 weeks (p = 0.002, p < 0.001 and p < 0.001), while ratios TNF-α/IL-10 and TNF-α/IL-1RA increased (p = 0.003 and p = 0.035). CRP increased by 12 % in participants with low to average CLIP (pre 1.91 ± 0.39 mg/L, post 2.13 ± 1.16 mg/L, p = 0.006) and decreased by 36 % in those with high CLIP (pre 5.14 mg/L ± 1.20, post 3.30 ± 2.29 mg/L, p < 0.001). Change in leptin and IL-1RA was positively associated with change in fat mass (β = 0.133, p < 0.001; β = 0.017, p < 0.001) and insulin resistance (β = 0.095, p = 0.024; β = 0.020, p = 0.001). Change in lean mass was not associated with any of the biomarkers., Conclusion: 13 weeks of combined lifestyle intervention, either with or without protein drink, reduced circulating adipokines and anti-inflammatory cytokine IL-1RA, and increased inflammatory ratios TNF-α/IL-10 and TNF-α/IL-1RA in older adults with obesity and T2D. Effect on CLIP was inversely related to baseline inflammatory status., Competing Interests: Declaration of competing interest JdV-vdB is an employee of Danone Nutricia Research. SW is an employee of the Netherlands Organisation for Applied Scientific Research (TNO), which is a not-for-profit research organisation collaborating in several public-private partnerships or business-to-business research projects that receive funding from companies. All other authors declare no conflicts of interest related to this research., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) showed cognitive benefits from a multidomain lifestyle intervention in at-risk older people. The LipiDiDiet trial highlighted benefits of medical food in prodromal Alzheimer's disease (AD). However, the feasibility and impact of multimodal interventions combining lifestyle with medical food in prodromal AD is unclear., Methods: MIND-AD mini was a 6-month multinational (Sweden, Finland, Germany, France) proof-of-concept randomized controlled trial (RCT). Participants were 60-85 years old, had prodromal AD (International Working Group-1 criteria), and vascular/lifestyle risk factors. The parallel-group RCT had three arms: multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); multimodal lifestyle intervention + medical food (Fortasyn Connect); and regular health advice/care (control). Participants were randomized 1:1:1 (computer-generated allocation at each site). Outcome evaluators were blinded to randomization. Primary outcome was feasibility of the multimodal intervention, evaluated by recruitment rate during a 6-month recruitment phase, overall adherence in each intervention arm, and 6-month retention rate. Successful adherence was pre-specified as attending ≥ 40% of sessions/domain in ≥ 2/4 domains (lifestyle intervention), and consuming ≥ 60% of the medical food (lifestyle intervention + medical food). The secondary outcomes included adherence/participation to each intervention component and overall adherence to healthy lifestyle changes, measured using a composite score for healthy lifestyle. Cognitive assessments were included as exploratory outcomes, e.g. Clinical Dementia Rating scale., Results: During September 2017-May 2019, 93 individuals were randomized (32 lifestyle intervention, 31 lifestyle + medical food, and 30 control group). Overall recruitment rate was 76.2% (64.8% during the first 6 months). Overall 6-month retention rate was 91.4% (lifestyle intervention 87.5%; lifestyle + medical food 90.3%; control 96.7%). Domain-specific adherence in the lifestyle intervention group was 71.9% to cognitive training, 78.1% exercise, 68.8% nutritional guidance, and 81.3% vascular risk management; and in the lifestyle + medical food group, 90.3% to cognitive training, 87.1% exercise, 80.7% nutritional guidance, 87.1% vascular risk management, and 87.1% medical food. Compared with control, both intervention arms showed healthy diet improvements (β Lifestyle×Time  = 1.11, P = 0.038; β Lifestyle+medical food×Time  = 1.43, P = 0.007); the lifestyle + medical food group also showed vascular risk reduction (P = 0.043) and less cognitive-functional decline (P < 0.05, exploratory analysis). There were 5 serious adverse events (control group: 1; lifestyle intervention: 3; lifestyle + medical food: 1) unrelated to interventions., Conclusions: The multidomain lifestyle intervention, alone or combined with medical food, had good feasibility and adherence in prodromal AD. Longer-term cognitive and other health benefits should be further investigated in a larger-scale trial., Trial Registration: ClinicalTrials.gov NCT03249688., (© 2024. The Author(s).)

The classic ketogenic diet is an effective treatment option for drug-resistant epilepsy, but its high fat content challenges patient compliance. Optimizing liver ketone production guided by a method comparing substrates for their ketogenic potential may help to reduce the fat content of the diet without loss in ketosis induction. Here, we present a liver cell assay measuring the β-hydroxybutyrate (βHB) yield from fatty acid substrates. Even chain albumin-conjugated fatty acids comprising between 4 and 18 carbon atoms showed a sigmoidal concentration-βHB response curve (CRC) whereas acetate and omega-3 PUFAs produced no CRC. While CRCs were not distinguished by their half-maximal effective concentration (EC50), they differed by maximum response, which related inversely to the carbon chain length and was highest for butyrate. The assay also suitably assessed the βHB yield from fatty acid blends detecting shifts in maximum response from exchanging medium chain fatty acids for long chain fatty acids. The assay further detected a dual role for butyrate and hexanoic acid as ketogenic substrate at high concentration and ketogenic enhancer at low concentration, augmenting the βHB yield from oleic acid and a fatty acid blend. The assay also found propionate to inhibit ketogenesis from oleic acid and a fatty acid blend at low physiological concentration. Although the in vitro assay shows promise as a tool to optimize the ketogenic yield of a fat blend, its predictive value requires human validation., (© 2024. The Author(s).)

Small intestine (SI) maturation during early life is pivotal in preventing the onset of gut diseases. In this study we interrogated the milestones of SI development by gene expression profiling and ingenuity pathway analyses. We identified a set of cytokines as main regulators of changes observed across different developmental stages. Upon cytokines stimulation, with IFNγ as the most contributing factor, human fetal organoids (HFOs) increase brush border gene expression and enzyme activity as well as trans -epithelial electrical resistance. Electron microscopy revealed developed brush border and loss of fetal cell characteristics in HFOs upon cytokine stimulation. We identified T cells as major source of IFNγ production in the fetal SI lamina propria. Co-culture of HFOs with T cells recapitulated the major effects of cytokine stimulation. Our findings underline pro-inflammatory cytokines derived from T cells as pivotal factors inducing functional SI maturation in vivo and capable of modulating the barrier maturation of HFOs in vitro ., Competing Interests: J.-N.B. is an employee of DNAnexus. I.B.R. is an employee of Danone Nutricia Research., (© 2024 The Authors.)

Beta-glucans and arabinoxylans are known for their immunostimulatory properties. However, in vivo these have been documented almost exclusively following parenteral administration, underemphasizing oral intake. C57BL/6 mice are fed either a control diet or a diet supplemented with yeast-derived whole β-glucan particle (yWGP) or with rice-derived arabinoxylan (rice bran-1) at a concentration of 1%, 2.5%, or 5% weight/weight (w/w) for 2 weeks. Thereafter, cells from blood, bone marrow, and spleen are collected for ex vivo stimulation with various microbial stimuli. Dietary intake of yWGP for 2 weeks at concentrations of 1% and 2.5% w/w increases ex vivo cytokine production in mouse blood and bone marrow, whereas 5% w/w yWGP shows no effect. In the spleen, cytokine production remains unaffected by yWGP. At a concentration of 1% w/w, rice bran-1 increases ex vivo cytokine production by whole blood, but 2.5% and 5% w/w cause inhibitory effects in bone marrow and spleen. This study demonstrates that dietary yWGP and rice bran-1 induce immune priming in mouse blood and bone marrow, with the strongest effects observed at 1% w/w. Future human trials should substantiate the efficacy of dietary β-glucans and arabinoxylans to bolster host immunity, focusing on dose optimization., (© 2024 The Authors. Molecular Nutrition & Food Research published by Wiley‐VCH GmbH.)

Introduction and Objectives: Food allergy has several negative nutritional consequences and may persist beyond the first year of lives. This study aimed to assess the role of a complete oral amino acid-based supplement in the diet of children on cow's milk protein elimination diet because of food allergy., Materials and Methods: This study included two groups of children aged 1-5 years paired by age and socioeconomic status: (1) study group, on cow's milk protein elimination diet plus an oral amino acid-based supplement, and (2) control group, on cow's milk protein elimination diet. Sociodemographic, clinical, anthropometric, and dietary data were obtained through online interviews. Two 24-h dietary recalls were collected on nonconsecutive days. Both groups comprised mostly boys., Results: The study group presented lower values of body mass index. The frequency of feeding difficulties was similar between groups. The study group had a higher intake of energy, protein, carbohydrates, calcium, iron, zinc, phosphorus, magnesium, copper, selenium, vitamins D, E, B1, B2, B6, and B12, niacin, and folic acid compared to the control group. A higher proportion of children in the study group had adequate intake according to the recommendations made for energy, carbohydrates, iron, phosphorus, selenium, vitamins A, D, E, B1, B2, and B6, and folic acid., Conclusions: The use of a complete oral amino acid-based supplement has a positive effect on the diet quality of preschoolers on cow's milk elimination diet because of food allergy, promoting higher intake of energy, calcium, vitamin D, and other essential nutrients., Competing Interests: Adriana Sanudo, Vanessa Cristina de Castro Rodrigues, and Mauro Batista de Morais received personal fees to develop this study. Thaysa Maués Cezar works the Medical Affairs Division of Danone Nutricia Brazil, and Camila Leonel Mendes de Abreu was working in the Medical Affairs Division of Danone Nutricia Brazil when this study was developed.

Early life microbiota encompasses of a large percentage of Bifidobacterium, while it is not sufficiently understood how the Bifidobacterium population develops after infant's birth. Current study investigated the longitudinal changes in Bifidobacterium population during the first two years of life in 196 term born infants (1,654 samples) using 16S rRNA-23S rRNA internal transcribed spacer (ITS) sequence analysis. Throughout the first two years of life, Bifidobacterium breve, Bifidobacterium longum subsp. longum and Bifidobacterium adolescentis were most dominant and prevalent in the Bifidobacterium population, while B. breve had the highest relative abundance and prevalence during the first week of life and it was taken over by B. longum subsp. longum around two years after birth. Sampling time points, early antibiotic(s) exposure (effect only measurable within a month after birth), delivery mode (effect still detectable two-months after birth) and feeding mode (effect lasted until six months after birth), significantly contributed to the overall variation in the bifidobacterial population. From six months onwards, introducing of solid food and cessation of breastfeeding were accompanied with drastic changes in the composition in bifidobacterial population. Altogether, current study confirmed the effect of potential contributors to the longitudinal changes within the bifidobacterial population during the first two years of life. Registered at https://clinicaltrials.gov: NCT02536560.

Parkinson's disease (PD) is a complex neurodegenerative disease which is often associated with gastrointestinal (GI) dysfunction. The GI tract is home to a wide range of microorganisms, among which bacteria, that can influence the host through various mechanisms. Products produced by these bacteria can act in the gut but can also exert effects in the brain via what is now well established to be the microbiota-gut-brain axis. In those with PD the gut-bacteria composition is often found to be different to that of non-PD individuals. In addition to compositional changes, the metabolic activity of the gut-microbiota is also changed in PD. Specifically, it is often reported that key producers of short chain fatty acids (SCFAs) as well as the concentration of SCFAs themselves are altered in the stool and blood of those with PD. These SCFAs, among which butyrate, are essential nutrients for the host and are a major energy source for epithelial cells of the GI tract. Additionally, butyrate plays a key role in regulating various host responses particularly in relation to inflammation. Studies have demonstrated that a reduction in butyrate levels can have a critical role in the onset and progression of PD. Furthermore, it has been shown that restoring butyrate levels in those with PD through methods such as probiotics, prebiotics, sodium butyrate supplementation, and fecal transplantation can have a beneficial effect on both motor and non-motor outcomes of the disease. This review presents an overview of evidence for the altered gut-bacteria composition and corresponding metabolite production in those with PD, with a particular focus on the SCFA butyrate. In addition to presenting current studies regarding SCFA in clinical and preclinical reports, evidence for the possibility to target butyrate production using microbiome based approaches in a therapeutic context is discussed., Competing Interests: Author JG is employed by Danone Nutricia Research. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elford, Becht, Garssen, Kraneveld and Perez-Pardo.)

Ever since the implementation of microfluidics in the biomedical field, in vitro models have experienced unprecedented progress that has led to a new generation of highly complex miniaturized cell culture platforms, known as Organs-on-a-Chip (OoC). These devices aim to emulate biologically relevant environments, encompassing perfusion and other mechanical and/or biochemical stimuli, to recapitulate key physiological events. While OoCs excel in simulating diverse organ functions, the integration of the immune organs and immune cells, though recent and challenging, is pivotal for a more comprehensive representation of human physiology. This comprehensive review covers the state of the art in the intricate landscape of immune OoC models, shedding light on the pivotal role of biofabrication technologies in bridging the gap between conceptual design and physiological relevance. The multifaceted aspects of immune cell behavior, crosstalk, and immune responses that are aimed to be replicated within microfluidic environments, emphasizing the need for precise biomimicry are explored. Furthermore, the latest breakthroughs and challenges of biofabrication technologies in immune OoC platforms are described, guiding researchers toward a deeper understanding of immune physiology and the development of more accurate and human predictive models for a.o., immune-related disorders, immune development, immune programming, and immune regulation., (© 2024 The Authors. Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Background and Purpose: Despite being associated with serious adverse outcomes, such as mortality, sarcopenia remains largely undiagnosed in older individuals. This study aimed to assess the awareness, practices, and barriers and enablers to clinical implementation of sarcopenia diagnosis and treatment among geriatric rehabilitation health care professionals in the Netherlands., Methods: As part of EMPOWER-GR, a cross-sectional survey among geriatric rehabilitation health care professionals working in the Netherlands was undertaken between September 23, 2020, and January 28, 2021. Professionals were recruited via a geriatric rehabilitation care provider, health care professional associations, professional networks of the research team, and social media. Descriptive statistics were used to assess the study outcomes., Results and Discussion: Of the 501 geriatric rehabilitation health care professionals, 12.2% were physicians, 23.0% physical therapist/occupational therapists, 30.3% dietitians, 19.6% nurses, and 11.0% health care assistants. The concept of sarcopenia was known by 83.8% of the participants, 92.5% correctly identified sarcopenia as low muscle mass and strength (and low physical performance), and 73.8% identified sarcopenia as very important in the management of older adults admitted for rehabilitation. Although 26.2% and 18.9% of the participants reported screening and diagnosing sarcopenia, respectively, in their current practice, only 3.0% adequately used the (revised) definition of the European Working Group on Sarcopenia in Older People. When sarcopenia has been diagnosed, 65.0% reported initiating treatment consisting of resistance exercise training (78.7%), food fortification/high-energy or protein diet (85.4%), and oral nutritional supplements (70.4%). Most important barriers to screening and diagnosis were lack of knowledge, access to tools, and equipment and time, while enablers were protocol implementation, access to training, and clear responsibilities., Conclusions: Sarcopenia awareness is high among geriatric rehabilitation health care professionals in the Netherlands, but adequate screening and diagnosis is almost nonexistent in current clinical practice, which hampers interventions. Better knowledge, clear responsibilities, and access to tools and protocols, as well as prioritization, are needed for sarcopenia to be diagnosed and treated in geriatric rehabilitation in the Netherlands., Competing Interests: A.B.M. reports grants from Danone Nutricia Research during the conduct of the study. J.P.v.W. reports that she is an employee of Danone Nutricia Research. L.M.G.V. and C.G.M.M. declare that they have no conflicts of interest. The collaboration project is co-funded by the PPP Allowance made available by Health∼Holland (TKI-LSHM19069-H049), Top Sector Life Sciences & Health, and Top Sector Agri & Food (LWV19287) to stimulate public-private partnerships, and includes an in-cash and in-kind contribution from Danone Nutricia Research. Vrije Universiteit, Amsterdam UMC, and Cordaan made in-kind contribution. All organizations are based in the Netherlands., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of Academy of Geriatric Physical Therapy, APTA.)

Background: The Rome Foundation Global Epidemiology Study (RFGES) found that 40.3% of adults in 26 internet-surveyed countries met Rome IV criteria for disorders of gut-brain interaction (DGBI). However, additional people not meeting DGBI criteria may also be burdened by frequent gastrointestinal symptoms., Aims: To explore the prevalence and demographic distribution of sub-diagnostic gastrointestinal symptoms, and the hypothesised associated effects on quality of life (QoL), life functioning and healthcare needs., Methods: We analysed data from the RFGES survey, which included the Rome IV diagnostic questionnaire and QoL, psychological, work productivity and healthcare questions., Results: Of the 50,033 people without a history of organic gastrointestinal disorders, 25.3% classified in the sub-diagnostic group (no DGBI but one or more frequent gastrointestinal symptoms), 41.4% had DGBI and 33.4% had no frequent gastrointestinal symptoms (non-GI group). Sub-diagnostic prevalence in different world regions ranged from 22.2% (North America) to 30.5% (Middle East), was slightly higher among males than females and decreased with age. The sub-diagnostic group was intermediate between the non-GI and DGBI groups, and significantly different from both of them on QoL, anxiety, depression, somatisation, healthcare utilisation and life and work impairment., Conclusions: One in four adults without organic gastrointestinal disorders or DGBI report frequent gastrointestinal symptoms. This sub-diagnostic group has reduced QoL, greater psychological and non-GI bodily symptoms, impaired work productivity and life activities and greater healthcare use compared to non-GI individuals. This suggests that many in this sub-diagnostic group might benefit from healthcare services or symptom self-management advice., (© 2024 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Semi-synthetic and grain-based diets are common rodent diets for biomedical research. Both diet types are considered nutritionally adequate to support breeding, growth, and long life, yet there are fundamental differences between them that may affect metabolic processes. We have characterized the effects of diet type on breeding outcomes, metabolic phenotype, and microbiota profile in adult mice. Healthy 8-week-old female and male C57BL/6J mice were fed a semi-synthetic or a grain-based diet for 12 weeks and changes in body weight and body composition were monitored. Breeding outcomes were determined. Body fat accumulation of female mice was lower on the semi-synthetic diet than on the grain-based diet. Pregnancy rate and newborn pup survival appeared to be lower in mice exposed to semi-synthetic diet compared to grain-based diet. Both female and male mice showed a profound change in fecal microbiota alpha and beta diversity depending on diet type. Our study shows that type of rodent diet may affect breeding outcomes whilst influencing metabolism and health of female laboratory mice. These factors have the potential to influence other experimental outcomes and the results suggest that semi-synthetic and grain-based diets are not interchangeable in research using rodent models. Careful consideration and increased understanding of the consequences of diet choice would lead to improvements in experimental design and reproducibility of study results., Competing Interests: “I have read the journal’s policy and the authors of this manuscript have the following competing interests: LS, ST, ET, JL, MR and LH are employees of the institution that funded the research or were at the time of the study (ET). This does not alter our adherence to PLOS ONE policies on sharing data and materials.”, (Copyright: © 2024 Schipper et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This multi-center prospective randomized controlled trial was a tolerance and safety study investigating the thickener locust bean gum (LBG) in infants with regurgitation, to support the re-evaluation of the safety of LBG in infant formula. The primary objective was to demonstrate that after an 8-week intervention, stool consistency was not inferior (i.e., was not looser or more watery) in infants fed an anti-regurgitation (AR) formula containing LBG vs. the stool consistency of infants fed with an unthickened control formula. A total of 103 full-term infants with regurgitation were randomized to the test or control formula. The test formula contained LBG (0.4 g/100 mL), short-chain galacto-oligosaccharides, and long-chain fructo-oligosaccharides (scGOS/lcFOS; 9:1; 0.4 g/100 mL) and postbiotics and the control formula contained scGOS/lcFOS (0.8 g/100 mL), the same amount of postbiotics, and did not contain LBG. The average stool consistency score at the 8th intervention week was the primary outcome parameter. Secondary outcome parameters were stool consistency at other timepoints, stool frequency, Infant Gastrointestinal Symptom Questionnaire (IGSQ) score, growth, (serious) adverse events ([S]AEs), regurgitation severity, and infant well-being. Overall, the infants were 36.9 ± 12.9 [mean ± SD] days old, 62.7% girls in the test, and 50.0% girls in the control group. The primary analysis showed that the test group did not have looser or more watery stools than the control group. IGSQ sum scores decreased comparably in both groups. The frequency of regurgitation was significantly lower in the test group compared to the control group (mixed model repeated measurement, p ≤ 0.028) and parent-reported well-being scores were favorable. Adequate growth was observed in both groups. Both products were well-tolerated and safe and the AR formula with LBG was efficacious in reducing regurgitation frequency. This study provides further evidence for the dietary management of regurgitation by LBG-containing formulae in infants who are not exclusively breastfed, and the reassurance it can bring to parents.

The objective of the present study is to assess the rates of acquired tolerance to cow's milk (CM) after 36 months in subjects who consumed amino acid-based formula with synbiotics (AAF-S) or amino acid-based formula without synbiotics (AAF) during a 1-year intervention period in early life as part of the PRESTO study (Netherlands Trial Register number NTR3725). Differences in CM tolerance development between groups were analysed using a logistic regression model. Results show that the proportion of subjects (mean [±SD] age, 3.8 ± 0.27 years) who developed CM tolerance after 36 months was similar in the group receiving AAF-S (47/60 [78%]) and in the group receiving AAF (49/66 [74%]) (p = 0.253), that is, figures comparable to natural outgrowth of CM allergy. Our data suggest that the consumption of AAF and absence of exposure to CM peptides do not slow down CM tolerance acquisition., (© 2024 The Authors. Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: In 2016, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use updated its efficacy guideline for good clinical practice and introduced predefined quality tolerance limits (QTLs) as a quality control in clinical trials. QTLs are complementary to Quality by Design (QbD) principles (ICH-E8) and are one of the components of the risk-based clinical trial quality management system., Methods: Currently the framework for QTLs process is well established, extensively describing the operational aspects of Defining, Monitoring and Reporting, but a single source of commonly used methods to establish QTLs and secondary limits is lacking. This paper will primarily focus on closing this gap and include applications of statistical process control and Bayesian methods on commonly used study level quality parameters such as premature treatment discontinuation, study discontinuation and significant protocol deviations as examples., Conclusions: Application of quality tolerance limits to parameters that correspond to critical to quality factors help identify systematic errors. Some situations pose special challenges to implementing QTLs and not all methods are optimal in every scenario. Early warning signals, in addition to QTL, are necessary to trigger actions to further minimize the possibility of an end-of-study excursion., (© 2023. The Author(s).)

Background: Exposure of the esophageal mucosa to food allergens can cause acute mucosal responses in patients with eosinophilic esophagitis (EoE), but the underlying local immune mechanisms driving these acute responses are not well understood., Objective: We sought to gain insight into the early transcriptomic changes that occur during an acute mucosal response to food allergens in EoE., Methods: Bulk RNA sequencing was performed on esophageal biopsy specimens from adult patients with EoE (n = 5) collected before and 20 minutes after intramucosal injection of various food extracts in the esophagus. Baseline biopsy specimens from control subjects without EoE (n = 5) were also included., Results: At baseline, the transcriptome of the patients with EoE showed increased expression of genes related to an EoE signature. After local food injection, we identified 40 genes with a potential role in the early immune response to food allergens (most notably CEBPB, IL1B, TNFSF18, PHLDA2, and SLC15A3). These 40 genes were enriched in processes related to immune activation, such as the acute-phase response, cellular responses to external stimuli, and cell population proliferation. TNFSF18 (also called GITRL), a member of the TNF superfamily that is best studied for its costimulatory effect on T cells, was the most dysregulated early EoE gene, showing a 12-fold increase compared with baseline and an 18-fold increase compared with a negative visual response. Further experiments showed that the esophageal epithelium may be an important source of TNFSF18 in EoE, which was rapidly induced by costimulating esophageal epithelial cells with the EoE-relevant cytokines IL-13 and TNF-α., Conclusions: Our data provide unprecedented insight into the transcriptomic changes that mediate the acute mucosal immune response to food allergens in EoE and suggest that TNFSF18 may be an important effector molecule in this response., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In addition to the elimination diet, dietary composition may influence disease severity in patients with eosinophilic esophagitis (EoE) through modulation of the immune response., Aim: To explore the immunomodulatory role of nutrition before and during elimination diet in adult EoE patients., Methods: Nutritional intake was assessed in 39 Dutch adult EoE patients participating in the Supplemental Elemental Trial (Dutch trial registry NL6014, NTR6778) using 3-day food diaries. In this randomized controlled trial, diagnosed patients received either a four-food elimination diet alone (FFED) or FFED with addition of an amino acid-based formula for 6 weeks. Multiple linear regression analyses were performed to assess associations between the intake of nutrients and food groups per 1000 kCal and peak eosinophil count/high power field (PEC), both at baseline and after 6 weeks., Results: At baseline, we found a statistically significant negative (thus favorable) relationship between the intake of protein, total fat, phosphorus, zinc, vitamin B12, folate, and milk products and PEC (p < .05), while calcium (p = .058) and full-fat cheese/curd (p = .056) were borderline (favorably) significant. In contrast, total carbohydrates, prepacked fruit juice, and white bread were significantly positively (unfavorable) related to PEC (p < .05), while ultra-processed meals (p = .059) were borderline (unfavorably) significant. After dietary intervention, coffee/tea were significantly negatively (favorably) related to PEC, hummus/legumes were significantly positively (unfavorably) related with PEC, while peanuts were borderline significantly positively related (p = .058)., Conclusion: Dietary composition may be related to inflammation in adult EoE patients. High-quality and anti-inflammatory diets may be a promising adjuvant therapy in the dietary management of EoE., (© 2024 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Supplementation is crucial for improving performance and health in phenylketonuria (PKU) patients, who face dietary challenges. Proteins are vital for athletes, supporting muscle growth, minimizing catabolism, and aiding muscle repair and glycogen replenishment post-exercise. However, PKU individuals must limit phenylalanine (Phe) intake, requiring supplementation with Phe-free amino acids or glycomacropeptides. Tailored to meet nutritional needs, these substitutes lack Phe but fulfill protein requirements. Due to limited supplement availability, athletes with PKU may need higher protein intake. Various factors affect tolerated Phe levels, including supplement quantity and age. Adhering to supplement regimens optimizes performance and addresses PKU challenges. Strategically-timed protein substitutes can safely enhance muscle synthesis and sports performance. Individualized intake is essential for optimal outcomes, recognizing proteins' multifaceted role. Here, we explore protein substitute supplementation in PKU patients within the context of physical activity, considering limited evidence.

Background: Sarcopenia is prevalent in 20-50% of geriatric rehabilitation inpatients and is associated with functional dependence and mortality. The aim is to assess knowledge of geriatric rehabilitation inpatients on sarcopenia and their willingness and perceived barriers to start treatment., Methods: Enhancing Muscle POWER in Geriatric Rehabilitation (EMPOWER-GR) is an observational cohort of geriatric rehabilitation inpatients in Amsterdam, the Netherlands. Knowledge of sarcopenia, willingness and perceived barriers to treatment were assessed with a survey among inpatients. Importance of and self-perceived muscle health were rated using a visual analogue scale from 0 to 10. Descriptive statistics were used., Results: Inpatients' (n = 157, 59.9% female) mean age was 80.5 years (SD 7.3). Sarcopenia (European Working Group on Sarcopenia in Older People 2) prevalence was 21.7%. Five inpatients (3.2%) had heard of sarcopenia and had knowledge of its definition. Median muscle health was rated as 6 (interquartile range: 4-7). After explanation of treatment options, 67.1% were willing to start resistance exercise training (RET), 61.1% a high-protein diet and 55.7% oral nutritional supplements (ONS). Inpatients with sarcopenia were less willing (51.6%) to start a high-protein diet compared with inpatients without sarcopenia (77.8%) (P = 0.002); there was no difference for RET and ONS. Most reported barriers to treatment were ONS dislike (17.0%), too many other health issues (13.6%), doubts about treatment effectiveness/importance (12.9%) and RET intensity/difficulty (10.2%)., Conclusions: Knowledge of sarcopenia was low, while the majority of inpatients showed willingness to start treatment. A dislike of ONS, RET difficulty and too many other health issues may reduce willingness to start treatment. Education is important to increase sarcopenia-related health issues in geriatric rehabilitation inpatients., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

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., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Estimating the shelf-life of vegetable oils is important to develop solutions to reduce spoilage by lipid oxidation. Typically, the shelf-life is predicted by detecting secondary oxidation markers in accelerated shelf-life tests, which are time-consuming. Existing numerical approaches using early primary oxidation products as predictive markers do not account for variations in fatty acid types, antioxidants, or storage conditions. A mechanistic kinetic model was developed incorporating these factors as a step towards shelf-life prediction for vegetable oils. Specific kinetic constants for the reactions of each unsaturated fatty acid type account for variations in fatty acid composition, and oxygen mass transfer accounts for variations in oxygen conditions. A second acceleration of lipid oxidation observed in long-term storage experiments was described by a multiplication factor for the kinetic constants related to oxidation products. Our model accurately extrapolates short-time experimental data to estimate long term formation of oxidation products under the same conditions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

(1) Background: The aim of the present paper was to study fetal and infant creatine (Cr) supply to improve nutrition and neuroprotection in term and especially in preterm infants. The primary outcomes were the placental Cr flux at the end of pregnancy and the time course of human milk (HM) Cr. (2) Methods: The estimation of placental Cr flux was based on umbilical arterial and venous cord blood Cr in 10 term infants after elective caesarian section. HM Cr, creatinine (Crn), and macronutrients were measured longitudinally in 10 mothers across the first 6 months of breastfeeding. (3) Results: At the end of pregnancy, the mean fetal Cr flux was negative (-2.07 mmol/min). HM Cr was highest in colostrum, decreased significantly within the first 2 weeks of breastfeeding ( p < 0.05), and did not change significantly thereafter. HM Cr was not correlated with HM Crn or macronutrient composition. (4) Conclusions: The present data suggest that fetal endogenous Cr synthesis covers the needs at the end of pregnancy. However, high colostrum Cr and HM Cr levels, independent of macronutrient composition, suggest that there may be a critical Cr demand immediately after birth that needs to be covered by enteral supply.

Objective: Obesity and excess adiposity are leading causes of metabolic and cardiovascular morbidity and mortality. Early identification of individuals at risk is key for preventive strategies. We examined the relationship between infant body composition (0-2 years of age) and later (>2 years) health outcomes using a systematic review., Design: We preregistered the study on PROSPERO (ID 288013) and searched Embase, PubMed and Cochrane databases for English language publications using the Medical Subject Headings (MeSH) terms 'infant' and 'body composition' and 'risk' between January 1946 and February 2022. We included studies which assessed infant body composition using predetermined in vivo methods other than body mass index (BMI)., Results: We identified 6015 articles. After abstract screening to assess eligibility, we reviewed 130 full text publications. 30 were included in the final assessment and narrative synthesis. Meta-analysis was not possible due to heterogeneity of results. All 30 studies were of high quality and reported associations between infant body composition and 19 different health outcomes after 2 years of age. Outcome measurements ranged from 2 years to 16 years. The strongest associations were found between infant fat mass and later fat mass (7 studies), and later BMI (5 studies). For 11 of the outcomes assessed, there was no relationship to infant adiposity detected., Conclusions: Current evidence, from a small number of studies, suggests a positive association between infant adiposity and future adiposity or BMI, but the validity of infant body composition as a biomarker of future health remains inconclusive. Carefully designed, standardised studies are required to identify the value of infant body composition for predicting later health., Trial Registration: PROSPERO: 288013., Competing Interests: Competing interests: FA was paid an honoraria to complete the work. C-YC is a full-time employee of ILSI Europe., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)