Kathryn Aston-Mourney

Beyond being one of the most widely prescribed medications for type 2 diabetes, metformin has been increasingly used during pregnancy for gestational diabetes and polyendocrine metabolic ovarian syndrome. While it is considered safe for pregnancy and lactation, metformin is known to induce gut microbial changes in non-pregnant individuals with type 2 diabetes, and maternal and offspring microbial alterations are known to influence offspring development. Therefore, understanding whether metformin drives microbiota changes beyond the confounding effects of maternal hyperglycaemia holds significant implications for maternal–foetal health. In this study, non-diabetic C57BL/6 mouse dams received either control or metformin treatment (5 mg/mL) in drinking water during pregnancy and lactation. Microbial profiling from faecal samples of dams at gestational day 15 and offspring at 6 weeks of age was analysed using 16S rRNA sequencing and an R-based pipeline. Metformin positively restructured dominant taxa associated with healthy pregnancy in dams, while inducing broad taxonomic changes in males and Bacteroidetes-dominant shifts in female offspring. Overall, maternal metformin treatment promoted short-chain fatty acid-producing taxa while suppressing potentially opportunistic bacteria, without compromising community richness. Further studies are required to elucidate the functional mechanisms underlying these shifts and their long-term implications for maternal–foetal health.

Over the past decades, gut microbiota has emerged as a critical modulator of human health and disease. Pregnancy involves substantial microbiota remodelling that influences offspring development, yet mechanisms linking maternal microbiota changes to gestational diabetes mellitus (GDM) remain unclear. The current literature lacks a comprehensive synthesis of pregnancy microbiota dynamics across healthy gestation to GDM, comparative human–murine analysis, and pregnancy-specific mechanistic frameworks distinct from type 2 diabetes models. This narrative review comprehensively synthesised evidence on gut microbiota composition in healthy pregnancy and GDM (2005–2025, NCBI PubMed) to identify convergent signatures and articulate pregnancy-specific mechanisms. Early pregnancy microbiota resembles non-pregnant individuals, whereas late pregnancy exhibits increased lactic acid-producing bacteria and reduced Firmicutes-to-Bacteroidetes (F/B) ratios. GDM exhibits pathological dysbiosis with elevated F/B ratios and reduced Bifidobacterium. Critically, GDM butyrate-producer patterns diverge from type 2 diabetes, suggesting pregnancy-specific mechanisms beyond glucose homeostasis. Despite these insights, methodological heterogeneity and cross-sectional designs constrain definitive conclusions. Longitudinal studies with standardised sequencing are essential to confirm consistent signatures and enable rational design of microbiota-modulating interventions (prebiotics, probiotics, synbiotics, postbiotics, diet) to optimise maternal health, prevent GDM, and support offspring development.

Amid growing consumer interest in the health benefits of anthocyanins, the market for anthocyanin-based dietary supplements has expanded substantially. However, data on product composition and health claims in the Australian online market remains limited. This study characterises anthocyanin-based dietary supplements available online in Australia (July–August 2024), examining product origin, botanical sources, formulation, extract concentration, delivery formats, anthocyanin content disclosure, health claims, serving sizes and pricing patterns. Among the 121 products analysed, bilberry, elderberry, and tart cherry were the most commonly used anthocyanin sources, collectively representing 47% of the market. Capsules were the dominant delivery format (86%), and reported extract concentrations varied widely, with lower ratios (1–10:1) being most prevalent. Only 18% of products disclosed anthocyanin content (0.1–36%), with bilberry supplements accounting for the majority of reported values. Health claims were present on 69% of products and varied by source, with bilberry products most frequently promoting vision health, elderberry emphasising immune support, tart cherry targeting joint and exercise recovery, and cranberry focusing on urinary tract health. Declared extract (mg per serving) ranged from 10 mg to >1500 mg. Pricing varied substantially across products (AUD 0.02–7.40 per gram; mean AUD 0.78/g), with bilberry supplements consistently among the most expensive. Overall, these findings highlight considerable variability in formulation, disclosure, and health claim practices, underscoring the need for improved transparency and evidence-aligned representation of anthocyanins as bioactive pigments in the Australian nutraceutical market.

Pancreatic β-cell dysfunction is the key driver of type 2 diabetes, and anthocyanins have been proposed as dietary compounds that may help preserve β-cell health. This systematic review aimed to synthesise evidence on the direct effects of anthocyanins on β-cell viability, apoptosis, oxidative stress, and insulin secretion across in vitro models. Four databases were searched in March–April 2025, and eighteen studies met the inclusion criteria. Purified anthocyanins—including cyanidin-3-glucoside (C3G), cyanidin-3-rutinoside (C3R), malvidin-3-glucoside (M3G), and delphinidin-3-glucoside (D3G)—as well as anthocyanin-rich berry extracts, were tested in INS-1, MIN6, RIN-m5F cells and primary mouse or human islets under glucotoxic, lipotoxic, oxidative, cytokine, and amyloidogenic stress. Anthocyanins consistently improved β-cell viability, reduced apoptosis, and lowered reactive oxygen species (ROS), nitric oxide (NO), and thiobarbituric acid reactive substances (TBARSs) levels while enhancing antioxidant enzyme activities. Multiple studies showed upregulation of insulin secretion-related genes and proteins, and both acute and chronic treatments increased glucose-stimulated insulin secretion under normal and stressed conditions. Mechanistic pathways involved modulation of mitogen-activated protein kinase (MAPK) signalling, endoplasmic reticulum (ER) stress responses, inflammatory mediators, and mitophagy (PINK1/PARKIN). While effective in vitro concentrations were higher than typical circulating levels, the collective evidence highlights anthocyanins as promising β-cell protective agents and underscores the need for studies examining their metabolites and physiologically relevant exposure.

Polyphenols, particularly anthocyanins, are associated with metabolic health benefits; however, whether anthocyanin extracts provide greater bioaccessibility than whole foods remain unclear. This study investigated the role of the food matrix in açaí berry, one of the richest natural sources of anthocyanins, by comparing polyphenol and anthocyanin bioaccessibility across freeze-dried whole fruit, crude extract, and purified extract. All samples underwent standardised INFOGEST in vitro digestion, and total polyphenol content (TPC), anthocyanins (ACN), and antioxidant activity were quantified using Folin–Ciocalteu, pH-differential, and DPPH assays, respectively. Intestinal-phase TPC % bioaccessibility was similar in whole fruit (58%) and crude extract (58%) but significantly lower in pure extract (43%). ACN bioaccessibility showed a pronounced matrix effect, with the highest retention in whole fruit (44%), followed by crude extract (32%), and the lowest retention in pure extract (12%). Antioxidant activity after intestinal digestion mirrored these patterns. Overall, these findings demonstrate that the natural açaí food matrix substantially preserves anthocyanin stability during digestion, resulting in higher bioaccessible levels than matrix-free extracts, suggesting that incorporating matrix components into anthocyanin-rich nutraceuticals may help support greater functional recovery during gastrointestinal digestion.

Excessive body weight is associated with many chronic metabolic diseases and weight loss, so far, remains the gold standard treatment. However, despite tremendous efforts exploring optimal treatments for obesity, many individuals find losing weight and maintaining a healthy body weight difficult. Weight loss is often not sustainable resulting in weight regain and subsequent efforts to lose weight. This cyclic pattern of weight loss and regain is termed “yoyo dieting” and predisposes individuals to obesity and metabolic comorbidities. How yoyo dieting might worsen obesity complications during the weight recurrence phase remains unclear. In particular, there is limited data on the role of the gut microbiome in yoyo dieting. Gut health distress, especially gut inflammation and microbiome perturbation, is strongly associated with metabolic dysfunction and disturbance of energy homeostasis in obesity. In this review, we summarise current evidence of the crosstalk between the gastrointestinal system and energy balance, and the effects of yoyo dieting on gut inflammation and gut microbiota reshaping. Finally, we focus on the potential effects of post-dieting weight loss in improving gut health and identify current knowledge gaps within the field, including gut-derived peptide hormones and their potential suitability as targets to combat weight regain, and how yoyo dieting and associated changes in the microbiome affect the gut barrier and the enteric nervous system, which largely remain to be determined.

Cyclic weight loss and subsequent regain after dieting and non-dieting periods, a phenomenon termed yoyo dieting, places individuals at greater risk of metabolic complications and alters gut microbiome composition. Resistant starch (RS) improves gut health and systemic metabolism. This study aimed to investigate the effect of yoyo dieting and RS on the metabolism and gut microbiome. C57BL/6 mice were assigned to 6 diets for 20 weeks, including control, high fat (HF), yoyo (alternating HF and control diets every 5 weeks), control with RS, HF with RS, and yoyo with RS. Metabolic outcomes and microbiota profiling using 16S rRNA sequencing were examined. Yoyo dieting resulted in short–term weight loss, which led to improved liver health and insulin tolerance but also a greater rate of weight gain compared to continuous HF feeding, as well as a different microbiota profile that was in an intermediate configuration between the control and HF states. Mice fed HF and yoyo diets supplemented with RS gained less weight than those fed without RS. RS supplementation in yoyo mice appeared to shift the gut microbiota composition closer to the control state. In conclusion, yoyo dieting leads to obesity relapse, and increased RS intake reduces weight gain and might help prevent rapid weight regain via gut microbiome restoration.

Anthocyanins have gained significant popularity in recent years for their diverse health benefits, yet their limited bioavailability poses a challenge. To address this concern, technologies have emerged to enhance anthocyanin concentration, often isolating these compounds from other food constituents. However, the extent to which isolated anthocyanins confer health benefits compared to their whole-food counterparts remains unclear. This review explores the current literature on anthocyanin bioavailability and metabolism in the body, with a focus on comparing bioavailability when consumed as extracts versus whole foods rich in anthocyanins, drawing from in vitro, in vivo, and human clinical studies. While direct comparisons between anthocyanin bioavailability in whole foods versus isolates are scarce, prevailing evidence favours whole-food consumption over anthocyanin extracts. Further clinical investigations, preferably with direct comparisons, are needed to validate these findings and elucidate the nuanced interplay between anthocyanins and food matrices, informing future research directions and practical recommendations.

Targeting β-cell failure could prevent, delay or even partially reverse Type 2 diabetes. However, development of such drugs is limited as the molecular pathogenesis is complex and incompletely understood. Further, while β-cell failure can be modeled experimentally, only some of the molecular changes will be pathogenic. Therefore, we used a novel approach to identify molecular pathways that are not only changed in a diabetes-like state but also are reversible and can be targeted by drugs. INS1E cells were cultured in high glucose (HG, 20 mM) for 72 h or HG for an initial 24 h followed by drug addition (exendin-4, metformin and sodium salicylate) for the remaining 48 h. RNAseq (Illumina TruSeq), gene set enrichment analysis (GSEA) and pathway analysis (using Broad Institute, Reactome, KEGG and Biocarta platforms) were used to identify changes in molecular pathways. HG decreased function and increased apoptosis in INS1E cells with drugs partially reversing these effects. HG resulted in upregulation of 109 pathways while drug treatment downregulated 44 pathways with 21 pathways in common. Interestingly, while hyperglycemia extensively upregulated metabolic pathways, they were not altered with drug treatment, rather pathways involved in the cell cycle featured more heavily. GSEA for hyperglycemia identified many known pathways validating the applicability of our cell model to human disease. However, only a fraction of these pathways were downregulated with drug treatment, highlighting the importance of considering druggable pathways. Overall, this provides a powerful approach and resource for identifying appropriate targets for the development of β-cell drugs. GRAPHICAL ABSTRACT