Unique trans-kingdom microbiome structural and functional signatures predict cognitive decline in older adults

Abstract

The prevalence of age-related cognitive disorders/dementia is increasing, and effective prevention and treatment interventions are lacking due to an incomplete understanding of aging neuropathophysiology. Emerging evidence suggests that abnormalities in gut microbiome are linked with age-related cognitive decline and getting acceptance as one of the pillars of the Geroscience hypothesis. However, the potential clinical importance of gut microbiome abnormalities in predicting the risk of cognitive decline in older adults is unclear. Till now the majority of clinical studies were done using 16S rRNA sequencing which only accounts for analyzing bacterial abundance, while lacking an understanding of other crucial microbial kingdoms, such as viruses, fungi, archaea, and the functional profiling of the microbiome community. Utilizing data and samples of older adults with mild cognitive impairment (MCI; n = 23) and cognitively healthy controls (n = 25). Our whole-genome metagenomic sequencing revealed that the gut of older adults with MCI harbors a less diverse microbiome with a specific increase in total viruses and a decrease in bacterial abundance compared with controls. The virome, bacteriome, and microbial metabolic signatures were significantly distinct in subjects with MCI versus controls. Selected bacteriome signatures show high predictive potential of cognitive dysfunction than virome signatures while combining virome and metabolic signatures with bacteriome boosts the prediction power. Altogether, the results from our pilot study indicate that trans-kingdom microbiome signatures are significantly distinct in MCI gut compared with controls and may have utility for predicting the risk of developing cognitive decline and dementia- debilitating public health problems in older adults.

Poor Oral Health Linked with Higher Risk of Alzheimer’s Disease

“…Therefore, future prospective studies should investigate oral pathogen load and inflammatory markers, such as interleukin (IL)-6, IL-1, and tumor necrosis factor-α, in patients with poor oral health and link them with AD pathologies, such as Aβ accumulation, CI, and neurofibrillary tangle formation. Emerging evidence is also suggesting connections between the oral microbiota and cognitive function [62,63], as well as between the gut microbiota and cognitive function [64,65]. Investigating the oral-gut axis and its effects on cognitive function and AD-like pathologies is also of interest in future studies.…”

Exploring the Influence of Gut–Brain Axis Modulation on Cognitive Health: A Comprehensive Review of Prebiotics, Probiotics, and Symbiotics

“…The microbiome–gut–brain axis is a complex system that describes interactions between the brain, the gut, and the microbiome [ 4 , 46 , 47 , 48 ]. There are numerous ways in which the microbiome and the brain interact, partially realized through direct neuronal, hormonal, and immune pathways [ 49 , 50 ].…”

“…During aging, the composition of the microbiome may change, influencing cognitive health [ 51 , 52 ]. As time progresses, microbiome diversity may decrease, potentially due to aging processes and cognitive decline [ 4 , 53 , 54 ]. Additionally, inflammatory processes may become more prevalent during aging [ 55 ], potentially harming brain structures and functions, indicating a bidirectional relationship.…”

“…The dietary habits and lifestyle of the Western civilized world have a significant impact on the gut microbiota, influencing cognitive functions [ 1 , 2 , 3 ]. Diets rich in added sugars and refined carbohydrates, with low fiber content and limited probiotic intake, can adversely affect the gut microbiota, potentially correlating with cognitive issues [ 1 , 4 ]. The prevalence of artificial additives, the consumption of pre-packaged, ultra-processed foods, and high-saturated fat diets can negatively influence both the gut microbiota and cognitive health and may be linked to cardiovascular problems as well [ 2 ].…”