Alzheimer's disease (AD) is a debilitating brain disorder with rapidly mounting prevalence worldwide, yet no proven AD cure has been discovered. Using a multi-omics approach in a transgenic AD mouse model, the current study demonstrated the efficacy of a modified Mediterranean-ketogenic diet (MkD) on AD-related neurocognitive pathophysiology and underlying mechanisms related to the gut-microbiome-brain axis. The findings revealed that MkD induces profound shifts in the gut microbiome community and microbial metabolites. Most notably, MkD promoted growth of the Lactobacillus population, resulting in increased bacteria-derived lactate production. We discovered elevated levels of microbiome- and diet-derived metabolites in the serum as well, signaling their influence on the brain. Importantly, these changes in serum metabolites upregulated specific receptors that have neuroprotective effects and induced alternations in neuroinflammatory-associated pathway profiles in hippocampus. Additionally, these metabolites displayed strong favorable co-regulation relationship with gut-brain integrity and inflammatory markers, as well as neurobehavioral outcomes. The findings underscore the ameliorative effects of MkD on AD-related neurological function and the underlying gut-brain communication via modulation of the gut microbiome-metabolome arrays.

Akkermansia muciniphila (A. muciniphila) and its derivatives, including extracellular vesicles (EVs) and outer membrane proteins, are recognized for enhancing intestinal balance and metabolic health. However, the mechanisms of Akkermansia muciniphila’s action and its effects on the microbiome are not well understood. In this study, we examined the influence of A. muciniphila and its derivatives on gastrointestinal (GI) and metabolic disorders through a meta-analysis of studies conducted on mouse models. A total of 39 eligible studies were identified through targeted searches on PubMed, Web of Science, Science Direct, and Embase until May 2024. A. muciniphila (alive or heat-killed) and its derivatives positively affected systemic and gut inflammation, liver enzyme level, glycemic response, and lipid profiles. The intervention increased the expression of tight-junction proteins in the gut, improving gut permeability in mouse models of GI and metabolic disorders. Regarding body weight, A. muciniphila and its derivatives prevented weight loss in animals with GI disorders while reducing body weight in mice with metabolic disorders. Sub-group analysis indicated that live bacteria had a more substantial effect on most analyzed biomarkers. Gut microbiome analysis using live A. muciniphila identified a co-occurrence cluster, including Desulfovibrio, Family XIII AD3011 group, and Candidatus Saccharimonas. Thus, enhancing the intestinal abundance of A. muciniphila and its gut microbial clusters may provide more robust health benefits for cardiometabolic, and age-related diseases compared with A. muciniphila alone. The mechanistic insight elucidated here will pave the way for further exploration and potential translational applications in human health.

The consumption of almonds has been associated with several health benefits, particularly concerning cardiovascular and intestinal health. In this comprehensive review, we compile and deliberate studies investigating the effects of almond consumption on cardiovascular disease (CVD) risk factors and gut health. Almonds are rich in monounsaturated fats, fiber, vitamins, minerals, and polyphenols, which contribute to their health-promoting properties. Regular intake of almonds has been shown to improve lipid profiles by reducing LDL cholesterol and enhancing HDL functionality. Additionally, almonds aid in glycemic control, blood pressure reduction, and chronic inflammation amelioration, which are critical for cardiovascular health. The antioxidant properties of almonds, primarily due to their high vitamin E content, help in reducing oxidative stress markers. Furthermore, almonds positively influence body composition by reducing body fat percentage and central adiposity and enhancing satiety, thus aiding in weight management. Herein, we also contemplate the emerging concept of the gut–heart axis, where almond consumption appears to modulate the gut microbiome, promoting the growth of beneficial bacteria and increasing short-chain fatty acid production, particularly butyrate. These effects collectively contribute to the anti-inflammatory and cardioprotective benefits of almonds. By encompassing these diverse aspects, we eventually provide a systematic and updated perspective on the multifaceted benefits of almond consumption for cardiovascular health and gut microbiome, corroborating their broader consideration in dietary guidelines and public health recommendations for CVD risk reduction.

Klebsiella pneumoniae is infamous for hospital-acquired infections and sepsis, which have also been linked to Alzheimer disease (AD)-related neuroinflammatory and neurodegenerative impairment. However, its causative and mechanistic role in AD pathology remains unstudied. A preclinical model of K. pneumoniae enteric infection and colonization is developed in an AD model (3xTg-AD mice) to investigate whether and how K. pneumoniae pathogenesis exacerbates neuropathogenesis via the gut-blood-brain axis. K. pneumoniae, particularly under antibiotic-induced dysbiosis, was able to translocate from the gut to the bloodstream by penetrating the gut epithelial barrier. Subsequently, K. pneumoniae infiltrated the brain by breaching the blood-brain barrier. Significant neuroinflammatory phenotype was observed in mice with K. pneumoniae brain infection. K. pneumoniae-infected mice also exhibited impaired neurobehavioral function and elevated total tau levels in the brain. Metagenomic analyses revealed an inverse correlation of K. pneumoniae with gut biome diversity and commensal bacteria, highlighting how antibiotic-induced dysbiosis triggers an enteroseptic “pathobiome” signature implicated in gut-brain perturbations. The findings demonstrate how infectious agents following hospital-acquired infections and consequent antibiotic regimen may induce gut dysbiosis and pathobiome and increase the risk of sepsis, thereby increasing the predisposition to neuroinflammatory and neurobehavioral impairments via breaching the gut-blood-brain barrier.

Western-style dietary patterns have been linked with obesity and associated metabolic disorders and gut dysbiosis, whereas prudent dietary and snacking choices mitigate these predispositions. Using a multi-omics approach, we investigated how almond snacking counters gut imbalances linked to adiposity and an average American Diet (AAD). Fifteen adults with overweight or obesity underwent a randomized, crossover-controlled feeding trial comparing a 4-week AAD with a similar isocaloric diet supplemented with 42.5 g/day of almonds (ALD). Almond snacking increases functional gut microbes, including Faecalibacterium prausnitzii, while suppressing opportunistic pathogens, thereby favorably modulating gut microecological niches through symbiotic and microbe-metabolite interactions. Moreover, ALD elevates health-beneficial monosaccharides and fosters bacterial consumption of amino acids, owing to enhanced microbial homeostasis. Additionally, ALD enhances metabolic homeostasis through a ketosis-like effect, reduces inflammation, and improves satiety-regulating hormones. The findings suggest that prudent dietary choices, such as almond snacking, promote gut microbial homeostasis while modulating immune metabolic state.