Cognitive Impairment Correlates with an Altered Gut Microbiome

Today's open access papers report on studies of the gut microbiome in older individuals exhibiting cognitive impairment. They add to a growing body of evidence for specific changes in the gut microbiome to contribute to age-related neurodegenerative conditions. The most obvious way in which this might happen is via a greater number of microbes capable of provoking a state of constant inflammation, either directly by engaging with the immune system, or more indirectly by contributing to dysfunction of the intestinal barrier, and thus allowing leakage of unwanted microbes and microbial metabolites into tissue. But it is also possible that loss of beneficial metabolites is a meaningful issue in later life.

The relative sizes of microbial populations making up the gut microbiome change with age, for reasons still under exploration, but in which the aging of the immune system may play a sizable role. The gut microbiome becomes more uniquely dysfunctional from individual to individual, but it is nonetheless the case that studies of cognitive decline and dementia are finding features of the gut microbiome that can be used to distinguish between healthy and cognitively impaired individuals.

It is not all that challenging to reset an aged gut microbiome via fecal microbiota transplantation from a young individual, at least not on an individual basis, without considering all of the overhead of regulatory approval. Fecal microbiota transplantation improves health and extends life in animal studies. There comes a point at which investigation must give way to clinical trials as a means to test whether restoration of a more youthful gut microbiome can meaningfully postpone neurodegenerative conditions; it seems a reasonable wager, given what is known.

Altered gut microbiota in older adults with mild cognitive impairment: a case-control study

Gut microbiota alterations in mild cognitive impairment (MCI) are inconsistent and remain to be understood. This study aims to investigate the gut microbial composition associated with MCI, cognitive functions, and structural brain differences. A nested case-control study was conducted in a community-based prospective cohort where detailed cognitive functions and structural brain images were collected. Thirty-one individuals with MCI were matched to sixty-five cognitively normal controls by age strata, gender, and urban/rural area. Fecal samples were examined using 16S ribosomal RNA (rRNA) sequencing. Compositional differences between the two groups were identified and correlated with the cognitive functions and volumes/thickness of brain structures.

There was no significant difference in alpha diversity and beta diversity between MCIs and cognitively normal older adults. However, the abundance of the genus Ruminococcus, Butyricimonas, and Oxalobacter decreased in MCI patients, while an increased abundance of nine other genera, such as Flavonifractor, were found in MCIs. Altered genera discriminated MCI patients well from controls and were associated with attention and executive function.

Gut microbiota and intestinal barrier function in subjects with cognitive impairments: a cross-sectional study

To investigate the differences in gut microbial composition, intestinal barrier function, and systemic inflammation in patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI), and normal control (NC) cases, a total of 118 subjects (45‚ÄČAD, 38 MCI, and 35 NC) were recruited. Cognitive function was assessed using Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment Scale (MoCA). Functional ability was assessed using Activity of Daily Living Scale (ADL). The composition of gut microbiome was examined by 16S rRNA high-throughput sequencing. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predict functional transfer of gut microbiota. Gut barrier dysfunction was evaluated by measuring the levels of diamine oxidase (DAO), D-lactic acid (DA), and endotoxin. The serum high-sensitivity C-reactive protein (hs-CRP) level was used to indicate systemic inflammation.

Compared with normal controls, patients with cognitive impairments (AD and MCI) had lower abundance of Dorea and higher levels of DAO, DA, and endotoxin. Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that the pathways related to glycan biosynthesis and metabolism increased in MCI patients, while the ones related to membrane transport decreased. The abundance of Bacteroides and Faecalibacterium was negatively correlated with the content of endotoxin, and positively correlated with the scores of MMSE and MoCA. The hs-CRP levels were similar among the three groups. A significant negative correlation was observed between the severity of gut barrier dysfunction and cognitive function.

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