Microbiome influences on neuro-immune interactions in neurodegenerative disease

Menees, Kelly B.; Otero, Brittney A.; Tansey, Malú G.

doi:10.1016/bs.irn.2022.07.006

Cited by 12 publications

(7 citation statements)

References 184 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…BBB dysregulation as a result of chronic inflammation, can be a result of signaling by peripheral TNF, allowing circulating immune cells to infiltrate into the parenchyma (40). In line with this, prior work from our team demonstrated that an HFHC diet impacts both the immune cell profile in circulation and within the CNS of the 5xFAD mouse model of AD (37).…”

Section: Introductionsupporting

confidence: 58%

“…Diets rich in specific fatty acids and sugars can lead to increased intestinal permeability and circulation of intestinal microbe-derived molecules with various effects on host physiology (34,35). Some of these bacterial components elicit inflammatory responses that can become chronic (36)(37)(38). Specifically, diets high in fat and carbohydrates (high-fat, highcarbohydrate; HFHC) increase the translocation of bacterial lipopolysaccharides, which strongly activate circulating lipopolysaccharide-binding protein (LBP) and trigger Toll-like receptor (TLR4)-mediated inflammation (39).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Diet-induced metabolic and immune impairments are sex-specifically modulated by soluble TNF signaling in the 5xFAD mouse model of Alzheimer’s disease

De Sousa Rodrigues,

Bolen,

Blackmer-Raynolds

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Emerging evidence indicates that high-fat, high carbohydrate diet (HFHC) impacts central pathological features of Alzheimer’s disease (AD) across both human incidences and animal models. However, the mechanisms underlying this association are poorly understood. Here, we identify compartment-specific metabolic and inflammatory dysregulations that are induced by HFHC diet in the 5xFAD mouse model of AD pathology. We observe that both male and female 5xFAD mice display exacerbated adiposity, cholesterolemia, and dysregulated insulin signaling. Independent of biological sex, HFHC diet also resulted in altered inflammatory cytokine profiles across the gastrointestinal, circulating, and central nervous systems (CNS) compartments demonstrating region-specific impacts of metabolic inflammation. In male mice, we note that HFHC triggered increases in amyloid beta, an observation not seen in female mice. Interestingly, inhibiting the inflammatory cytokine, soluble tumor necrosis factor (TNF) with the brain-permeant soluble TNF inhibitor XPro1595 was able to restore aspects of HFHC-induced metabolic inflammation, but only in male mice. Targeted transcriptomics of CNS regions revealed that inhibition of soluble TNF was sufficient to alter expression of hippocampal and cortical genes associated with beneficial immune and metabolic responses. Collectively, these results suggest that HFHC diet impairs metabolic and inflammatory pathways in an AD-relevant genotype and that soluble TNF has sex-dependent roles in modulating these pathways across anatomical compartments. Modulation of energy homeostasis and inflammation may provide new therapeutic avenues for AD.HighlightsHFHC diet triggers metabolic and inflammatory dysregulation in 5xFAD miceAβ42 and Aβ40 increase in the CNS of male 5xFAD mice fed a HFHC diet.SolTNF inhibition partially reverts HFHC diet-induced metabolic and inflammatory dysregulation in male, but not female, 5xFAD mice.

show abstract

Section: Introductionsupporting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Diet-induced metabolic and immune impairments are sex-specifically modulated by soluble TNF signaling in the 5xFAD mouse model of Alzheimer’s disease

De Sousa Rodrigues,

Bolen,

Blackmer-Raynolds

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Moreover, treatment of pregnant women, children or adults with sodium butyrate or other probiotics, alone or in combination with other proposed effective agents such as antipurinergics, or peptidergic (e.g., oxytocin) or the amino acid taurine, may be suggested [45]. This suggestion is in line with established microbiome influences on neuroimmune interactions and recent advocacy of probiotics use as a treatment strategy for multiple sclerosis, another neurodegenerative disease [151,152].…”

Section: Pb -Asd -Therapeuticsmentioning

confidence: 90%

Interaction of Heavy Metal Lead with Gut Microbiota: Implications for Autism Spectrum Disorder

Tizabi¹,

Bennani²,

Kouhen³

et al. 2023

Preprint

View full text Add to dashboard Cite

Autism Spectrum Disorder (ASD), a neurodevelopmental disorder characterized by persistent deficits in social interaction and social communication manifests in early childhood and is followed by significant impairment in social and occupational functions in adolescence and adulthood. Although genetics have been implicated, the exact causes of ASD have yet to be fully characterized. New evidence suggests that dysbiosis or perturbation in gut microbiota (GM) and exposure to lead (Pb) may play important roles in ASD etiology. Pb is a toxic heavy metal that has been linked to a wide range of negative health outcomes including anemia, encephalopathy, gastroenteric diseases and more importantly cognitive and behavioral problems inherent to ASD. Pb exposure can disrupt GM, which is essential for maintaining overall health. GM, consisting of trillions of microorganisms, has been shown to play a crucial role in the development of various physiological and psychological functions. GM interacts with the brain in a bidirectional manner referred to as “Gut-Brain Axis (GBA).” In this review, following a general overview of ASD and GM, the interaction of Pb with GM in the context of ASD is emphasized. Potential exploitation of this interaction for therapeutic purposes is also touched upon.

show abstract

“…Approximately 70-80% of immune cells are found in the gut. Mediators derived from the gut microbiome, including short-chain fatty acids (SCFAs) and other metabolites, lipopolysaccharides (LPS), and neurotransmitters, can affect neuro-immune interactions and the pathways by which these interactions may occur [7]. There is a complex bidirectional interaction between the intestinal microbiome and AD [8].…”

Section: Introductionmentioning

confidence: 99%

The Influence of the Gut Microbiota on Alzheimer's Disease: A Narrative Review

Yin¹,

Xu²,

Jin³

et al. 2023

J. Integr. Neurosci.

View full text Add to dashboard Cite

Alzheimer's disease (AD) is a common neurodegenerative disease that tends to occur in the elderly. The main symptom is hypomnesia. More and more older people are suffering from this disease worldwide. By 2050, 152 million people worldwide are expected to have AD. It is thought that the aggregation of amyloid-beta peptides and hyper-phosphorylated tau tangles contribute to AD. The microbiotagut-brain (MGB) axis appears as a new concept. The MGB axis is a collection of microbial molecules produced in the gastrointestinal tract that influence the physiological function of the brain. In this review, we discuss how the gut microbiota (GM) and its metabolites affect AD in different ways. Dysregulation of the GM has been shown to be involved in various mechanisms involved in memory and learning functions. We review the current literature on the role of the entero-brain axis in the pathogenesis of AD and its potential role as a future therapeutic target in the treatment and/or prevention of AD.

show abstract

Microbiome influences on neuro-immune interactions in neurodegenerative disease

Cited by 12 publications

References 184 publications

Diet-induced metabolic and immune impairments are sex-specifically modulated by soluble TNF signaling in the 5xFAD mouse model of Alzheimer’s disease

Diet-induced metabolic and immune impairments are sex-specifically modulated by soluble TNF signaling in the 5xFAD mouse model of Alzheimer’s disease

Interaction of Heavy Metal Lead with Gut Microbiota: Implications for Autism Spectrum Disorder

The Influence of the Gut Microbiota on Alzheimer's Disease: A Narrative Review

Contact Info

Product

Resources

About