SfN19: How might the gut–brain connection impact brain health in mice?

Written by Kimberley Ndungu (Future Science Group)

Recent studies have suggested that intestinal bacteria imbalance has a role in disorders such as Alzheimer’s disease (AD) and traumatic brain injury. Having an increased understanding of the gut–brain connection via the immune system may help in developing new treatments for neurodegenerative diseases.

At SfN Neuroscience 2019 (19–23 October, Chicago, IL, USA), the abstracts of four studies investigating the impact of gut–brain communication on brain health in mice were presented.

“These are important contributions to our understanding of the complex relationship between the gut and the brain,” commented press conference moderator, Jane A Foster (McMaster University, Ontario, Canada).


Gut microbiome changes induced by antibiotic treatment may reduce amyloid-β (Aβ) plaques in mice and alter microglia

Researchers from the University of Chicago Medicine (IL, USA) have discovered a potential relationship between changes in the microbiome and AD pathology.

Using two transgenic mouse models of Aβ amyloidosis, the team of researchers established a strong association between the gut microbiome and cerebral Aβ plaque pathology as well as plaque-localized gliosis.

The team performed fecal microbiota transplantation in male mice that had received long-term treatment of antibiotics. Furthermore, they performed fecal transfer from male to female mice to investigate for any sex-specific differences.

Changes in the mice’s microbiome caused by antibiotic treatment reduced Aβ pathology and altered microglia characteristics in males, however, there was no change in females. Reversing the antibiotic’s effect in males reversed their symptoms.

The findings suggest that the gut microbiome influences microglia, neuroinflammation and Alzheimer’s pathology in a sex-specific manner.

Abstract: Dodiya HB, Kuntz T, Shaik SM et al. Sex-specific effects of microbiome perturbations on cerebral abeta amyloidosis and microglia phenotypes in an Alzheimer’s transgenic mouse model. Presented at: SfN Neuroscience, Chicago, IL, USA, 19–23 October 2019.


A health-promoting probiotic could improve intestinal imbalances in mice with AD

Currently, the impact of gut microbe metabolites, such as short-chain fatty acids (SCFAs), on brain health is unknown. Therefore, a team of researchers investigated the role of SCFAs in gut–brain communication

Using a mouse model with AD the researchers administered health-promoting probiotics to investigate the effect of changes of gut bacteria on the brain. In mice who received the probiotic treatment the team observed an increase in neuronal activity and bacterial byproducts.

After they analyzed SCFAs in serum and brains of the mice, the researchers discovered significantly higher hippocampal levels of SFCAs in mice that received probiotic treatment.

The findings from this study suggest that that a bacterial imbalance exists in AD and correlates with changes in SFCAs in the brain.

Abstract: Kaur H, Golovko MY, Darland DC, Combs CK. Effects of probiotic supplementation on serum and brain short chain fatty acids in the AppNL-G-F mouse model of Alzheimer’s disease. Presented at: SfN Neuroscience, Chicago, IL, USA, 19–23 October 2019.


Could a probiotic treatment be used as a novel therapy for traumatic brain injury?

Abnormalities in bowel function are common among patients with traumatic brain injuries (TBIs), therefore, gut dysfunction and dysbiosis have been suggested to play a role in the development of TBI pathology.

Using mouse models with TBI, the team of researchers investigated the ability of probiotic treatment to protect brain function. They discovered that the mice who received the treatment no longer exhibited memory deficits and had a significantly higher diverse gut microbiome compared with mice without the treatment.

The findings from this study suggest that gut dysbiosis contributes to TBI pathogenesis and holds potential of being a novel therapeutic target for treating brain injury.

Abstract: Amaral WZ, Ying LZ, Gomez-Pinilla F. Probiotic therapeutics prevent neurological and cognitive deficits in traumatic brain injury in mice. Presented at: SfN Neuroscience, Chicago, IL, USA, 19–23 October 2019.


Diet-induced obesity in mice may alter immune signaling, triggering changes in blood–brain barrier permeability

TNF – a cytokine that is elevated in AD patients – regulates the permeability and inflammation of both the gut barrier and blood–brain barrier. A team of researchers hypothesized that soluble TNF is a key contributor to AD pathology and metabolic dysfunction.

The team fed AD mouse models a high-fat diet to examine whether diet-induced obesity alters the immune cell population. After 4 weeks of diet, the researchers selectively inhibited soluble TNF signaling using XPro1595 – a blood–brain barrier permanent peptide.

The findings demonstrated that inhibiting soluble TNF enhanced diet-induced increase in Aβ and T cells in their brain, suggesting that diet impacts immune cell population via soluble TNF and may enhance neuroinflammation and neurodegeneration in AD.

Abstract: Tansey MGT, Macpherson KP, Eidson LN et al. Soluble TNF mediates obesogenic diet-induced alterations in peripheral and brain immunophenotype in a mouse model of Alzheimer’s disease. Presented at: SfN Neuroscience, Chicago, IL, USA, 19–23 October 2019.


Source: Society for Neuroscience. Using the gut–brain connection to impact brain health and disease. Press release: www.sfn.org/Meetings/Neuroscience-2019

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