Omics Points to a Role for the Gut Microbiome in Aging of the Hippocampus

Some of the metabolites produced by the gut microbiome aid function in the brain. For example, there is good evidence for butyrate produced by the microbiome to improve neurogenesis in the brain via modulating expression of BDNF. Unfortunately, the amounts of a number of beneficial metabolites produced by the gut microbiome declines with age, while harmful metabolites and inflammatory signaling increases. Researchers here gather data to support a role in the hippocampus specifically for a number of metabolites that originate in the gut microbiome, the area of the brain most involved in memory function. This and many other lines of research suggest that more attention should be given to the development of therapies capable of lasting restoration of a more youthful gut microbiome, such as fecal microbiota transplantation.

Aging is an intricate biological event that occurs in both vertebrates and invertebrates. During the aging process, the brain, a vulnerable organ, undergoes structural and functional alterations, resulting in behavioral changes. The hippocampus has long been known to be critically associated with cognitive impairment, dementia, and Alzheimer's disease during aging; however, the underlying mechanisms remain largely unknown. In this study, we hypothesized that altered metabolic and gene expression profiles promote the aging process in the hippocampus. Behavioral tests showed that exploration, locomotion, learning, and memory activities were reduced in aged mice.

Metabolomics analysis identified 69 differentially abundant metabolites and showed that the abundance of amino acids, lipids, and microbiota-derived metabolites (MDMs) was significantly altered in hippocampal tissue of aged animals. Our metabolomic analysis identified many known MDMs, including short-chain fatty acids, indoles, phenols, nucleotides, and amino acids. Intriguingly, the abundance of several MDMs, such as TMAO and spermidine, was significantly changed in the hippocampus of aging mice. Furthermore, transcriptomic analysis identified 376 differentially expressed genes in the aged hippocampus. The multi-omics analysis showed that pathways related to inflammation, microglial activation, synapse, cell death, cellular/tissue homeostasis, and metabolism were dysregulated in the aging hippocampus.

In conclusion, our data revealed that metabolic perturbations and gene expression alterations in the aged hippocampus were possibly linked to their behavioral changes in aged mice; we also provide evidence that altered MDMs might mediate the interaction between gut and brain during the aging process.



Fecal microbiota transplantation is simply not available to the general public, at least for healthy people after 50-60. There is also high variability of microbiome compositions, e.g. between different ethnic groups, and, as the result, reports of compatibility complications.

There is a much simpler option, cheap and readily available to anyone who wants to try it - polyphenols. Extracts of all mainstream berries can be bought in chemist stores or online. However, the dosage is a grey area - too small will have little effect, too much will act as a strong antibiotic. They also all act differently, e.g. blueberries extract significantly boosts lacto and bifidobacteria in just under a week, but also some undesirable bacteria like candida. Extracts of green tea (catechins) or pomegranate (ellagitannins) significantly suppress undesirable bacteria, also in just under a week, but in the end harm lacto bacteria. So, it becomes a balancing act.

It would be great if there are more human studies on polyphenols with specific recommendations on type and dosage.

Posted by: Evgeny at December 3rd, 2022 1:39 AM
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