Abstract Ulcerative colitis (UC) is a debilitating, immune-mediated inflammatory disorder of the gastrointestinal (GI) tract with far-reaching consequences on distal organs, including the bone marrow. Here, we describe the molecular mechanisms that contribute to UC-induced abnormal hematopoiesis. We show that chronic UC drives HSPC differentiation toward myelopoiesis in an APE1/Ref-1/HIF-1α/IL-1r1-dependent manner. Blockade of the redox-activity of APE1/Ref-1 with APX3330 inhibits the elevated expression of HIF-1α in HSPCs and reverses the aberrant HSPC dynamics under the inflammatory milieu of UC, including suppression of pro-inflammatory Ly6Chi monocytes. Using echinomycin, we pharmacologically blocked HIF-1α activity and found that HIF-1α mediates inflammatory responses via downstream IL-1r1 signaling. Blockade of the redox activity of ref-1 rescues the abnormal HSPC function. Our data highlight the significance of the APE1/Ref-1/HIF-1α/IL-1r1 signaling cascade in aberrant hematopoiesis that contributes to the pathophysiology of chronic UC through a feed-forward loop.

Dietary fibres display substantial structural heterogeneity which modulate physiological processes across multiple organ systems. Although structure–functional–health relationships are increasingly recognised, quantitative models linking molecular signatures to functional performance remain limited. This study applied Raman and Fourier-transform infrared spectroscopy (FTIR) to acquire vibrational fingerprints from ten dietary fibres, followed by chemometric processing via principal component analysis, linear discriminant analysis, and partial least squares regression. Chemometric analyses robustly differentiated fibre samples according to chemical composition. Regression models constructed from Raman and FTIR spectra established strong structure–function correlations in the calibration data (R2 > 0.9). However, external validation with five independent fibre samples showed that the models had lower predictive power. Raman spectroscopy delivered accurate predictions of water holding capacity in three samples and water swelling capacity for two, whereas FTIR accurately predicted water swelling capacity of three samples and water holding capacity for one. Oil holding capacity was not predictable from both techniques, showing limitations in capturing lipophilic interactions via vibrational modes alone. These results demonstrate the utility of vibrational spectroscopy coupled with chemometrics as a rapid, non-destructive platform for screening dietary fibre functional potential. Future models can be refined by integrating supplementary properties such as particle size, porosity, or crystallinity. This methodology offers a valuable tool for accelerating the identification of therapeutic fibres in functional food development.

The human diet plays a pivotal role in health, yet many studies seeking to identify health-promoting foods rely on experimental designs that poorly reflect natural circumstances. The effects of dietary fibres on the microbiota are typically examined using pooled faecal material and isolated fibres, creating unrealistic environments. Additionally, little progress has been made in distinctly characterising the fermentation rates of dietary fibres. To evaluate the temporal dynamics of gut microbial composition and metabolite production, as well as to characterise the fermentation rates of dietary fibres at an individual level, we conducted an n-of-1 longitudinal study examining responses to eight distinct dietary fibres, fermented both individually and in combination. A blend of sugarcane fibre and cassava resistant starch produced significantly higher butyrate levels (p < 0.0001) than either fibre alone. Microbial profiling showed that inulin and pectin selectively enriched Bifidobacterium spp. Anaerobutyricum hallii was increased with psyllium husk, wheat dextrin, and banana resistant starch, but decreased with a mixture of sugarcane fibre and cassava resistant starch (p < 0.0001). Fermentation kinetics were distinctly categorised into "fast", "medium", "slow" and "poorly-fermentable". These findings indicate that combinations of dietary fibres can be used as a strategy to engineer synergistic health-promoting metabolite responses in an individual, while establishing a standardised framework for describing fermentation rates across studies.

Emerging evidence suggests that food additives may contribute to disease by inducing gut dysbiosis. However, previous studies have been criticized for using unrealistic doses and not testing for the potential synergistic effect of consuming multiple food additive simultaneously, which is how they are consumed under real-life conditions. This study aimed to determine whether eight previously implicated food additives directly promote dysbiosis, individually and in combination, at physiologically relevant doses. The results showed that none of the food additives significantly affected short-chain fatty acid production or the four characteristics of dysbiosis: loss of beneficial bacteria, expansion of pathobionts, reduction in bacterial diversity, and changes in microbial community structure. Moreover, there were no indications of the previously proposed synergistic effect. Results also highlighted the importance of fecal microbiota intra-variability and how it may cause false positives. While intra-variability was accounted for in this study, it is possible that the chosen gut microbiota was resilient to food-additive-induced dysbiosis. This is the first study to have examined both the individual and combined direct effect of the eight chosen food additives at physiologically relevant doses.

Dietary patterns have been identified as one of the most important modifiable risk factors for several non-communicable diseases, inextricably linked to the health span of older people. Poor dietary choices may act as triggers for immune responses such as aggravated inflammatory reactions and oxidative stress contributing to the pathophysiology of several ageing hallmarks. Novel dietary interventions are being explored to restore gut microbiota balance and promote overall health in ageing populations. Probiotics and, most recently, postbiotics, which are products of probiotic fermentation, have been reported to modulate different signalling biomolecules involved in immunity, metabolism, inflammation, and oxidation pathways. This review presents evidence-based literature on the effects of postbiotics in promoting healthy ageing and mitigating various age-related diseases. The development of postbiotic-based therapeutics and diet-based interventions within a personalised microbiota-targeted approach is proposed as a possible direction for improving health in the elderly population. Despite growing evidence, the data regarding their exact mechanistic pathways for antioxidant and immunomodulating activities remain largely unexplored. Expanding our understanding of the mechanistic and chemical determinants of postbiotics could contribute to disease management approaches, as well as the development of and optimisation of biotherapeutics.

Soluble dietary fibre (SDF) provides a range of health benefits, from supporting digestive health and managing cholesterol to aiding in weight control and strengthening immunity. Its adaptability allows it to enhance food texture, stability, and satiety. However, unlike insoluble dietary fibre (IDF), SDF is scarce in natural sources and often found in low amounts, so modifying dietary fibre (DF) is a promising approach to increase SDF levels in foods. With a growing focus on sustainability, the food industry is increasingly turning to eco-friendly modification techniques to boost SDF content and improve its functional properties. This review explores recent advancements in sustainable methods for SDF production, including enzyme treatments, microbial fermentation, extrusion, microwave, ultrasound, high hydrostatic pressure, high-pressure homogenisation, steam explosion, and the use of green chemicals. Each technique's mechanisms, benefits, and challenges are discussed alongside the health benefits and potential industrial applications of SDF. Sustainable modification methods have shown significant potential to raise SDF yield and enhance its physical and chemical properties, with a lower environmental impact than conventional chemical treatments. Techniques such as enzyme treatment, extrusion, high hydrostatic pressure, steam explosion, and green chemical use appear especially promising for meeting industry demands for sustainable, high-SDF food products. While microbial fermentation, microwave, ultrasound, and high-pressure homogenisation also offer advantages, they remain costly and challenging to scale for large-scale production.

Starch, a primary carbohydrate in staple foods, consists of amylose and amylopectin and plays a critical role in human metabolism. However, native starch exhibits limitations in the food industry, such as poor stability and high retrogradation rates, prompting the need for various modification techniques. The global rise in hyperglycemia-related disorders has driven research into strategies for controlling glucose release into the bloodstream. The rate of starch digestion in the small intestine influences blood glucose and insulin responses, with rapidly digestible starch (RDS) causing spikes, while slowly digestible starch (SDS) helps maintain steady levels. Resistant starch (RS), which passes undigested into the large intestine, offers benefits for managing obesity, cardiovascular diseases, and type 2 diabetes. Incorporating SDS into foods can slow gastric emptying and reduce the glycemic index, offering numerous health advantages. Understanding the molecular mechanisms behind SDS is essential given the increasing demand for functional foods. This review explores starch digestion, strategies for enhancing SDS content in foods, its applications, and the associated health benefits, aiming to guide future research in this evolving field.

Sustainability concerns have increased consumer demand for non-animal-derived proteins and the search for novel, alternative protein sources. The nutritional sustainability of the food system without compromising the nutrient quality, composition, digestibility and consumption is pivotal. As with farmed livestock, it is imperative to ensure the well-being and food security of companion animals and to develop sustainable and affordable pet foods. The current pilot study was conducted to determine the effect of greenhouse gas-derived novel, fermented protein ingredient in beagle dogs. The greenhouse gas-derived fermented protein is an alternative protein ingredient with optimal nutritional factors and provides traceability, significantly optimizes the use of land and water, and provides sustainability to the feed value chain of canine diets. Three experimental groups including control, 5 and 10% inclusion of high protein ingredients were included in the study and the results suggest that the fermented protein is palatable and acceptable at 5 and 10% inclusions in the diets of dogs. The present study shows no significant difference in general alertness, clinical symptoms, water consumption and social behavior of dogs between 5 and 10% fermented protein inclusion in canine diets. The diversity of the bacterial community did not change after supplementation with the tested protein source in dogs. Only a few bacterial genera differed significantly in relative abundance between the experimental groups. Feed consumption, faecal scoring and the microbiome data results of this pilot study on the use of novel, methane gas derived, bacterial SCP as a protein ingredient in the canine diets, would pave way for more and more inclusion of such novel alternative protein sources in the pet food industry.

Despite evolving definitions, dietary fibre classifications remain simplistic, often reduced to soluble and insoluble types. This binary system overlooks the complexity of fibre structures and their diverse health effects. Indeed, soluble fibre is not just soluble but has important qualities such as fermentability, attenuating insulin secretion, and lowering serum cholesterol. However, this limited classification fails to account for dietary fibre diversity and predict their full range of physiological effects. This article proposes a holistic classification framework that accounts for different fibre types and can be used to accurately infer their physiological outcomes. This proposed classification framework comprises of five constituents: backbone structure, water-holding-capacity, structural charge, fibre matrix and fermentation rate. This model more accurately captures the structural and functional diversity of dietary fibres, offering a refined approach to predicting their health benefits.

Aging is associated with alterations in gut microbiota, yet the combined effects of geography and diet remain underexplored in elderly populations. This study investigated the gut microbiota of 227 healthy Vietnamese individuals aged ≥60 years, stratified by select urban and rural residence in both Hanoi and Thanh Hoa provinces, and across three age groups (60–69, 70–79, ≥80 years). Dietary patterns were collected and recorded for each participant. 16S rRNA gene sequencing revealed significant differences in microbial diversity and composition associated with geographical location (urban, rural) and age. Urban participants in Hanoi exhibited higher richness and greater abundance of health-associated genera, including Bifidobacterium, Fusicatenibacter, and Blautia, likely reflecting more diverse plant-based diets. In contrast, rural participants in Thanh Hoa showed enrichment of beneficial butyrate-producing genera such as Fusicatenibacter, Roseburia, Lachnospira and Blautia, possibly linked to traditional diets rich in freshwater fish and fermented foods. Participants aged 70–79 years displayed reduced microbial richness compared to other age groups. Age-related reductions in Roseburia, Veillonella, and Prevotella were also observed. These findings highlight how geography, diet, and aging shape the gut microbiota and may guide microbiota-targeted dietary strategies to promote healthy aging.

The modern Western diet is dominated by ultra-processed food (UPF), which is increasingly linked to adverse health outcomes. Previous reviews have already identified problematic components of UPF, such as added fats and sugars. Therefore, the aim of this review was to provide a nuanced understanding of another ubiquitous component of UPF, food additives, and to explore any potential health risks associated with their consumption, as well as strategies for mitigating those risks. To provide real-world contextualization, we first quantified the food additive profile a person would be exposed to when consuming a popular UPF, the burger. Here we show that the selected burgers contain up to thirty-six different additives, primarily emulsifiers, thickeners, preservatives, and colours. While some reviewed additives, such as resistant starch and natural colours, have beneficial effects, the majority have a deleterious effect on health. However, limitations of current studies and gaps in government regulations complicate the assessment of the long-term health implications of a diet high in food additives. This review underscores the need for greater transparency in food labelling and a re-evaluation of food additive safety standards. It advocates for both elimination of certain food additives and reformulation strategies to mitigate potential health risks associated with UPF consumption. However, since elimination poses multiple challenges, reformulation may be a more realistic strategy. This could include fortification with fibre, replacing synthetic colours with natural colours, and reducing the use of preservatives by utilising advancements in hurdle technology.

Summary Globally, 60% of protein consumption comes from plant‐based sources. By exploring the potential of plant‐based proteins and incorporating them into diverse food options, we can not only enhance the sustainability of our food systems but also contribute to a more balanced and environmentally conscious society. Due to the limited availability of conventional food proteins, there has been a persistent exploration for alternative legume sources for addressing the need for protein‐based foods. Faba bean is a type of pulse that stands out among other legumes due to its high protein content (26.1%) and dietary fibre (25.0%). Faba beans and their derivatives have been suggested as potentially beneficial foods for individuals with diabetes and hypertension. However, faba beans contain some antinutritional factors (ANFs). These antinutrients can have adverse effects on digestion and nutrient absorption. Various strategies like thermal and non‐thermal processing methods have been employed to reduce the ANF content and improve nutritional functionality in faba beans. The applications of faba beans and their potential as replacements for traditional ingredients in various food products are described. By utilising processed fava bean products, novel food formulations and applications can be created, catering to the growing demand for healthier and functional food options.

Current treatments for inflammatory bowel disease (IBD) are often inadequate due to limited efficacy and toxicity, leading to surgical resection in refractory cases. IBD’s broad and complex pathogenesis involving the immune system, enteric nervous system, microbiome, and oxidative stress requires more effective therapeutic strategies. In this study, we investigated the therapeutic potential of bone marrow-derived mesenchymal stem cell (BM-MSC) treatments in spontaneous chronic colitis using the Winnie mouse model which closely replicates the presentation and inflammatory profile of ulcerative colitis. The 14-day BM-MSC treatment regimen reduced the severity of colitis, leading to the attenuation of diarrheal symptoms and recovery in body mass. Morphological and histological abnormalities in the colon were also alleviated. Transcriptomic analysis demonstrated that BM-MSC treatment led to alterations in gene expression profiles primarily downregulating genes related to inflammation, including pro-inflammatory cytokines, chemokines and other biomarkers of inflammation. Further evaluation of immune cell populations using immunohistochemistry revealed a reduction in leukocyte infiltration upon BM-MSC treatment. Notably, enteric neuronal gene signatures were the most impacted by BM-MSC treatment, which correlated with the restoration of neuronal density in the myenteric ganglia. Moreover, BM-MSCs exhibited neuroprotective effects against oxidative stress-induced neuronal loss through antioxidant mechanisms, including the reduction of mitochondrial-derived superoxide and attenuation of oxidative stress-induced HMGB1 translocation, potentially relying on MSC-derived SOD1. These findings suggest that BM-MSCs hold promise as a therapeutic intervention to mitigate chronic colitis by exerting anti-inflammatory effects and protecting the enteric nervous system from oxidative stress-induced damage.

Over the past half a century the Western diet (WD) has become saturated with food additives. During the same time, there has been an increase in Western diseases, such as inflammatory bowel disease (IBD) and metabolic syndrome (MetS). Emerging research has shown that food additives may be implicated in these diseases. However, critics have suggested that some of this research is problematic and may cause unnecessary fear amongst consumers. Here we review the emerging research concerning food additives and their implication in IBD and MetS, and criticisms thereof. To make the review more relevant to the WD, we only included common food additives, selected using supermarket data. Over a dozen common food additives from four categories were identified for their potential role in directly promoting these diseases. A consistent limitation of the research was the use of unrealistic human exposure conditions, such as high doses and modes of administration, as well as a lack of human trials. Another limitation was the absence of studies investigating the potential synergetic effect of consuming multiple food additives, as is common in the WD. Despite the limitations, there is some evidence that common food additives may be contributing to these additives, especially via their dysbiotic effect on the gut microbiota.

The gut microbiome is involved in the pathogenesis of many diseases including polycystic ovarian syndrome (PCOS). Modulating the gut microbiome can lead to eubiosis and treatment of various metabolic conditions. However, there is no proper study assessing the delivery of microbial technology for the treatment of such conditions. The present study involves the development of guar gum-pectin-based solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing curcumin (CCM) and fecal microbiota extract (FME) for the treatment of PCOS. The optimized S-SNEDDS containing FME and CCM was prepared by dissolving CCM (25 mg) in an isotropic mixture consisting of Labrafil M 1944 CS, Transcutol P, and Tween-80 and solidified using lactose monohydrate, aerosil-200, guar gum, and pectin (colon-targeted CCM solid self-nanoemulsifying drug delivery system [CCM-CT-S-SNEDDS]). Pharmacokinetic and pharmacodynamic evaluation was carried out on letrozole-induced female Wistar rats. The results of pharmacokinetic studies indicated about 13.11 and 23.48-fold increase in AUC of CCM-loaded colon-targeted S-SNEDDS without FME (CCM-CT-S-SNEDDS (WFME)) and CCM-loaded colon-targeted S-SNEDDS with FME [(CCM-CT-S-SNEDDS (FME)) as compared to unprocessed CCM. The pharmacodynamic study indicated excellent recovery/reversal in the rats treated with CCM-CT-S-SNEDDS low and high dose containing FME (group 13 and group 14) in a dose-dependent manner. The developed formulation showcasing its improved bioavailability, targeted action, and therapeutic activity in ameliorating PCOS can be utilized as an adjuvant therapy for developing a dosage form, scale-up, and technology transfer.

This study establishes mirdametinib as the first MEK inhibitor that can undergo clinical development for psychiatric indications such as post-traumatic stress disorder (PTSD). PTSD is characterized by persistent traumatic memories with limited effective treatment options. A body of evidence suggests that memory storage is dynamic and constantly updated through post-retrieval modification a process termed reconsolidation. Although ERK/MAPK signaling plays a central role in fear memory consolidation, no clinically translatable MEK inhibitor has been tested in experimental models or in clinical trials to disrupt this process. Furthermore, there is need to develop pharmacological and behavioral strategies to labilize the memory to make it susceptible for disruption. Here, we disrupted fear memory reconsolidation with the clinically relevant MEK inhibitor mirdametinib in C57BL/6 mice and tested memory destabilization strategies using an auditory fear conditioning paradigm, with drugs administered following reactivation of memory. We found prediction error effective in labilizing weak fear memory and combined D-cycloserine (DCS) and predication error effective in labilizing strong fear memory. Mirdametinib disrupted the weak fear memory and reduced ERK phosphorylation in lateral amygdala when coupled with prediction error at the time of memory reactivation but required coordinated combination of DCS, prediction error and mirdametinib to disrupt strong fear memory. Barnes maze spatial memory test and open field test revealed that mirdametinib did not affect retrieval of other forms (spatial) of long-term memory and locomotor activity. Furthermore, the effect of mirdametinib was specific to reconsolidation as it had no effect on fear memory when given without reactivation. These translational findings identify a new drug that can be adapted for the treatment of PTSD.

Abstract ID 96167Poster Board 483The escalating global prevalence of inflammatory bowel diseases (IBDs), comprising ulcerative colitis and Crohn’s disease, poses a considerable burden on public health. Despite therapeutic advances, persistent inflammation and associated complications underscore the limitations of current medical approaches. Fucoidans, fucose-rich sulfated polysaccharides found in edible brown algae, exhibit promising anti-inflammatory properties. However, variations in bioactivities and efficacy among fucoidans from distinct seaweeds warrant comprehensive investigation.Methods: This study systematically assessed the therapeutic potential of fucoidan extracts from Undaria pinnatifida (UPF) and Fucus vesiculosus (FVF) in a murine model of Dextran Sulfate Sodium (DSS)-induced acute colitis. Daily monitoring of colitis severity, coupled with macroscopic evaluation of collected colons and spleens, provided a comprehensive understanding. Histological scrutiny, utilising Hematoxylin and Eosin (H&E staining), and quantification of cytokines via enzyme-linked immunosorbent assay (ELISA) were integral components of our rigorous methodologyResults: Oral administration of UPF and FVF over seven days significantly mitigated body weight loss, improved the Disease Activity Index (DAI), and reduced colon and spleen weight compared to their DSS-treated counterparts. DSS-induced mice exhibited notable histological abnormalities, including loss of crypt architecture, goblet cells, immune cell infiltration, and edema, all of which were effectively reversed by UPF and FVF supplementation. Importantly, the macroscopic improvements correlated with a substantial reduction in the production of 18 pro-inflammatory cytokines in distal colon (DC) tissues. The findings propose the potential of orally administered UPF and FVF as a nutraceutical alternative for IBD treatmentThis research was funded by Marinova Pty Ltd, Hobart, Australia, grant number 00003944