Dietary advanced glycation end-products (AGEs) are a heterogeneous group of compounds formed when reducing sugars are heated with proteins, amino acids, or lipids at high temperatures for a prolonged period. The presence and accumulation of AGEs in numerous cell types and tissues are known to be prevalent in the pathology of many diseases. Modern diets, which contain a high proportion of processed foods and therefore a high level of AGE, cause deleterious effects leading to a multitude of unregulated intracellular and extracellular signalling and inflammatory pathways. Currently, many studies focus on investigating the chemical and structural aspects of AGEs and how they affect the metabolism and the cardiovascular and renal systems. Studies have also shown that AGEs affect the digestive system. However, there is no complete picture of the implication of AGEs in this area. The gastrointestinal tract is not only the first and principal site for the digestion and absorption of dietary AGEs but also one of the most susceptible organs to AGEs, which may exert many local and systemic effects. In this review, we summarise the current evidence of the association between a high-AGE diet and poor health outcomes, with a special focus on the relationship between dietary AGEs and alterations in the gastrointestinal structure, modifications in enteric neurons, and microbiota reshaping.

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.

Machine Learning (ML) models have been used to predict common mental disorders (CMDs) and may provide insights into the key modifiable factors that can identify and predict CMD risk and be targeted through interventions. This systematic review aimed to synthesise evidence from ML studies predicting CMDs, evaluate their performance, and establish the potential benefit of incorporating lifestyle data in ML models alongside biological and/or demographic-environmental factors. This systematic review adheres to the PRISMA statement (Prospero CRD42023401194). Databases searched included MEDLINE, EMBASE, PsycInfo, IEEE Xplore, Engineering Village, Web of Science, and Scopus from database inception to 28/08/24. Included studies used ML methods with feature importance to predict CMDs in adults. Risk of bias (ROB) was assessed using PROBAST. Model performance metrics were compared. The ten most important variables reported by each study were assigned to broader categories to evaluate their frequency across studies. 117 studies were included (111 model development-only, 16 development and validation). Deep learning methods showed best accuracy for predicting CMD cases. Studies commonly incorporated features from multiple categories (n = 56), and frequently identified demographic-environmental predictors in their top ten most important variables (63/69 models). These tended to be in combination with psycho-social and biological variables (n = 15). Lifestyle data were infrequently examined as sole predictors of CMDs across included studies (4.27 %). Studies commonly had high heterogeneity and ROB ratings. This review is the first to evaluate the utility of diagnostic ML for CMDs, assess their ROB, and evaluate predictor types. CMDs were able to be predicted, however studies had high ROB and lifestyle data were underutilised, precluding full identification of a robust predictor set.

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.

Background: Obesity is associated with structural deterioration in the gut. Yoyo dieting, which refers to repeated phases of dieting and non-dieting periods leading to cyclic weight loss and regain, is a common occurrence in individuals with obesity. However, there is limited evidence on how gut structures are affected in yoyo dieting. There is good evidence suggesting that increased intake of resistant starch (RS) may be beneficial in promoting structural improvements in the gut. This investigation aimed to explore the effect of yoyo dieting on gastrointestinal structure and whether RS has beneficial effects in improving obesity-related gastrointestinal damage. Method: In this study, male and female C57BL/6 mice were assigned to six different diets for 20 weeks: (1) control diet, (2) high fat diet (HF), (3) yoyo diet (alternating HF and control diets every 5 weeks), (4) control diet with RS, (5) HF with RS, and (6) yoyo diet with RS. Distal colon was collected for epithelial barrier integrity measurement. The small and large intestines were collected for histological assessment. Results: After 20 weeks, yoyo dieting resulted in increased colonic inflammation and exacerbated mucosal damage in comparison with continuous HF diet feeding. RS supplemented in HF and yoyo diets reduced mucosal damage in comparison to diets without RS. However, RS supplementation in a control diet significantly increased inflammation, crypt length, and goblet cell density. There were no significant differences in epithelial change and epithelial barrier integrity across diet groups. Conclusions: This study suggests that yoyo dieting worsens gut damage, and incorporating high levels of RS may be detrimental in the absence of dietary challenge.