Ian Rowland’s research while affiliated with University of Reading and other places

Age-associated decline of nuclear factor erythroid 2-related factor 2 (Nrf2) activity and DNA repair efficiency leads to the accumulation of DNA damage and increased risk of cancer. Understanding the mechanisms behind increased levels of damaged DNA is crucial for developing interventions to mitigate age-related cancer risk. Associated with various health benefits, (poly)phenols and their microbially mediated phenolic catabolites represent a potential means to reduce DNA damage. Four colonic-microbiota-derived phenolic catabolites were investigated for their ability to reduce H2O2-induced oxidative DNA damage and modulate the Nrf2-Antixoidant Response Element (ARE) pathway, in normal (CCD 841 CoN) and adenocarcinoma (HT29) colonocyte cell lines. Each catabolite demonstrated significant (p < .001) genoprotective activity and modulation of key genes in the Nrf2-ARE pathway. Overall, the colon-derived phenolic metabolites, when assessed at physiologically relevant concentrations, reduced DNA damage in both normal and adenocarcinoma colonic cells in response to oxidative challenge, mediated in part via upregulation of the Nrf2-ARE pathway.

Ageing is associated with a decline in both Nrf2 activity and DNA repair efficiency, leading to the accumulation of DNA damage and an increased risk of cancer. Understanding the mechanisms behind the increased level of damaged DNA during ageing is crucial for developing interventions to mitigate age-related cancer risk and improve overall health in older individuals. (Poly)phenols are plant-derived bioactive compounds that undergo metabolism into simpler phenolic catabolites following ingestion. While these compounds have been associated with various health benefits, further analysis of their bioavailable catabolites is necessary. To this end, four phenolic catabolites derived from colonic microbiota were investigated for their ability to reduce DNA damage in response to oxidative challenge and modulate the Nrf2-Antixoidant Response Element pathway. Normal and adenocarcinoma colonocyte cell lines (CCD 841 CoN, & HT29 respectively) were exposed to sub cytotoxic concentrations (>10 µM,) of hydroxylated (4-hydroxybenzoic acid, 3-(3’-hydroxyphenyl) propionic acid) and non-hydroxylated (benzoic acid or 3-phenylpropionic acid) phenolic acids. Using the COMET assay, each catabolite demonstrated significant (p<0.001) geno-protective activity, albeit with varying potency. They also significantly modulated expression of key genes in the Nrf2-ARE pathway, including Nrf2, Heme oxygenase-1 (HO-1), and NAD(P)H dehydrogenase quinone 1 (NQO1). Hydroxylation of the phenolic acids appeared to have a limited effect with respect to bioactivity. Overall, the colon derived phenolic metabolites, when assessed at physiologically relevant concentrations, reduced DNA damage in both normal and adenocarcinoma colonic cells in response to oxidative challenge, mediated – at least in part via upregulation of the Nrf2-ARE pathway.

Concerns for human and planetary health have led to a shift towards healthier plant-based diets. Plant-based dairy alternatives (PBDA) have experienced exponential market growth due to their lower environmental impact compared to dairy products. However, questions have arisen regarding their suitability as dairy substitutes and their role in food-based dietary guidelines (FBDG). Our study aimed to analyse the nutritional profiles of leading PBDA across Europe and compare them with their dairy counterparts. We examined the nutritional profiles of 309 unflavoured PBDA representing the European market leaders, including 249 plant-based drinks (PBD) and 52 plant-based alternatives to yogurt (PBAY). PBD and PBAY, excluding coconut varieties, were low in saturated fat (<1 g per serving). Seventy percent of PBDA were unsweetened, and most had sugar levels comparable to dairy. Except for soya varieties, PBDA protein levels were lower than dairy. Organic PBDA lacked micronutrients due to legal restrictions on fortification. Among non-organic PBDA, 76% were fortified with calcium, 66% with vitamin D, and 60% with vitamin B12. Less than half were fortified with vitamin B2, and a few with iodine (11%) and vitamin A (6%). PBAY were less frequently fortified compared to PBD. PBDA displayed a favourable macronutrient profile despite lower protein levels, which would be compensated for by other protein-dense foods in a usual mixed diet. Enhancing fortification consistency with dairy-associated micronutrients would address concerns regarding PBDA’s integration into FBDG. Our analysis supports the inclusion of fortified PBDA in environmentally sustainable FBDG for healthy populations.

Plant-based foods are increasing in popularity as more and more people are concerned about personal and planetary health. The consumption of plant-based dairy alternatives (PBDAs) has assumed a more significant dietary role in populations shifting to more sustainable eating habits. Plant-based drinks (PBDs) made from soya and other legumes have ample protein levels. PBDs that are appropriately fortified have adequate levels of important vitamins and minerals comparable to dairy milk. For the PBDs examined, the greenhouse gas emissions were diminished by 59–71% per 250 mL, and the land use and eutrophication impact was markedly less than the levels displayed by dairy milk. The water usage for the oat and soya drinks, but not rice drinks, was substantially lower compared to dairy milk. When one substitutes the 250 mL serving of dairy milk allowed within the EAT Lancet Planetary Health Diet for a fortified plant-based drink, we found that the nutritional status is not compromised but the environmental footprint is reduced. Combining a nutrient density score with an environmental index can easily lead to a misclassification of food when the full nutrition profile is not utilized or only a selection of environmental factors is used. Many PBDAs have been categorized as ultra-processed foods (UPFs). Such a classification, with the implied adverse nutritional and health associations, is inconsistent with current findings regarding the nutritional quality of such products and may discourage people from transitioning to a plant-based diet with its health and environmental advantages.

Probiotics and prebiotics have been the subject of extensive investigations into their role in human health including their effects on risk of age-related chronic diseases. There is good evidence that probiotics and, to a lesser extent prebiotics, can influence immune function in older subjects and counteract immunosenescence and increased inflammation. Probiotics have also been shown to increase the effectiveness of influenza vaccination in the elderly and reduce risk and/or duration of upper respiratory tract infections. Prebiotics and probiotics have been shown to have benefits for common gastrointestinal disorders that are common in older people, especially constipation, and there is some evidence that symptoms of metabolic syndrome can be alleviated by certain probiotics.

Key learnings from this review: • The gut microbiota can influence and modulate the health of the individual, and its composition and metabolism are affected by dietary patterns. • Comparisons between individuals or populations consuming plant-based and Western diets have shown differences in composition and/or metabolic activity of gut microbiota. • Little consistency in the specific types of bacteria involved due to: o variability in composition or characterization of plant-based diets (these cover a spectrum that includes vegan, vegetarian, flexitarian, Mediterranean, etc.) o methodological differences in assessing microbiota o large variation in microbiota composition between individuals • There are indications that plant-based diets may be more beneficial for the gut microbiota. • There is some consensus that the increased fibre intake associated with many plant-based diets is an important factor in the changes seen in microbiota composition and metabolism • Higher intake of dietary fibre is leading to increases of short-chain fatty acid (SCFA)-producing bacteria in many studies. SCFAs have several identified benefits: o Strengthen the intestinal epithelial layer, helping the immune system against pathogenic bacteria. o May improve energy metabolism and leanness. o Increase colonic motility and decrease visceral pain. o Have antiproliferative properties in cancer cells with a potentially favourable role in colon cancer. • Plant-based diets are also associated with high levels of polyphenols, which have been shown to beneficially modify the gut microbiota composition. They are extensively metabolized by the microbiota into potentially beneficial derivatives. • Plant-based diets are associated with reduced formation of potentially deleterious bacterial metabolites such as secondary bile acids, indole and p-cresol, and the proatherogenic compound trimethylamine oxide (TMAO) • When it comes to which diet is best for the gut microbiota, this scientific update shows that we are still far from being able to provide definitive advice. However, balanced diets focused on a variety of plant-based foods have the potential to positively modify gut microbiota composition and metabolism through increased intake of fibre and polyphenols and reduced intake of animal products.

POLICIES FOR ACHIEVING HEALTHY SUSTAINABLE DIETS 1. EU Green Deal, alternative proteins and dietary shift - Dr Cindy Schoumacher– EU policy officer 2. Where are we now? Sustainability gaps in the UK & EU - Dr Rosemary Green, Associate Professor in Sustainability, UK MOVING FROM POLICIES TO PRACTICE 3. Persuasion and nudging towards healthier diets: bacis and pitfalls - Professor Tim Smits, University Leuven, Belgium 4. Encouraging behavioural shifts towards sustainable diets: understanding intention-behaviour gaps - Dr Katie Laffan, University College Dublin, Ireland 5. Front-of-Package nutrition labelling and healthy food choice: opportunities and difficulties. Dr Iina-Maija Ikonen, Assistant Professor in Marketing, University of Bath 6. Communicating the environmental impact of recipes: the potential of apps and ecolabels - Dr Christian Reynolds, City University, London, UK 7. Promoting Sustainable Healthy Eating among Families – focus on food waste - Dr Jess Haines, University of Guelph, Canada Overall key messages: • Food systems have considerable influence on health and environment as well as the economy, cultural and socio-economic factors. To achieve health and environmental sustainable targets, substantial changes are needed in the way we farm, produce, transport, package, retail and advertise food as well as in consumer dietary behaviour • Reductions in the intake of animal food sources and avoidable food waste are critical together with a shift towards more healthy plant-based eating • Favourable trends in food consumption towards this are appearing across the globe, but the pace of change is slow. Innovative, evidence-based strategies and government policies are essential to further shift the dial towards diets that can sustain both human and planetary health What’s in the report: • short summary of each of the 7 presentations • infographics with key messages of each talk • links to watch the presentations on demand

Seaweeds are potentially sustainable crops and are receiving significant interest because of their rich bioactive compound content; including fatty acids, polyphenols, carotenoids, and complex polysaccharides. However, there is little information on the in vivo effects on gut health of the polysaccharides and their low-molecular-weight derivatives. Herein, we describe the first investigation into the prebiotic potential of low-molecular-weight polysaccharides (LMWPs) derived from alginate and agar in order to validate their in vivo efficacy. We conducted a randomized; placebo-controlled trial testing the impact of alginate and agar LWMPs on faecal weight and other markers of gut health and on composition of gut microbiota. We show that these LMWPs led to significantly increased faecal bulk (20-30%). Analysis of gut microbiome composition by sequencing indicated no significant changes attributable to treatment at the phylum and family level, although FISH analysis showed an increase in Faecalibacterium prausnitzii in subjects consuming agar LMWP. Sequence analysis of gut bacteria corroborated with the FISH data, indicating that alginate and agar LWMPs do not alter human gut microbiome health markers. Crucially, our findings suggest an urgent need for robust and rigorous human in vivo testing-in particular, using refined seaweed extracts. Citation: Bannon C.D.; Eckenberger, J.; Snelling, W.J.; Huseyin, C.E.; Allsopp, P.; Strain, C.; Ramnani, P.; Chitarrari, R.; Grant, J.; Hotchkiss, S.; et al. Low-Molecular-Weight