Gut microbes shape microglia and cognitive function during malnutrition

Bauer, Kylynda C.; York, Elisa M.; Cirstea, Mihai; Radisavljevic, Nina; Petersen, Charisse; Huus, Kelsey E.; Brown, Eric; Bozorgmehr, Tahereh; Berdún, Rebeca; Bernier, Louis‐Philippe; Lee, Ahwon; Woodward, Sarah E.; Krekhno, Zakhar; Han, Jun; Hancock, Robert E. W.; Ayala, Victòria; MacVicar, Brian A.

doi:10.1002/glia.24139

Cited by 12 publications

(8 citation statements)

References 119 publications

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“…Beyond locomotion, we assessed cognitive function and anxiety-like behaviors, via the Y maze and OFT ( 48 , 51 ), respectively. In each Y maze assessment, SV and HV mice displayed normal spontaneous alternation (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…5G and fig. s13F), ( 17 , 51 ). Cholinergic vagal activity maintains liver immune tolerance dampening pro-inflammatory and cytotoxic T cell responses.…”

Section: Resultsmentioning

confidence: 99%

“…Following facility acclimatization, vagotomized HCC mice underwent a battery of established behavioral tests, including phenotyping, open field test (OFT), and Y-maze (Fig. 4A) (48,50,51). To address neurological behaviors elicited by vagotomy versus tumor, a "Baseline" series of tests were performed prior to RIL175 tumor implantation.…”

Section: Vagotomy Benefits Neurological Function In Hcc Tumor-bearing...mentioning

confidence: 99%

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The Gut Microbiome Controls Liver Tumors via the Vagus Nerve

Bauer,

Trehan,

Ruf

et al. 2024

Preprint

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Liver cancer ranks amongst the deadliest cancers. Nerves have emerged as an understudied regulator of tumor progression. The parasympathetic vagus nerve influences systemic immunity via acetylcholine (ACh). Whether cholinergic neuroimmune interactions influence hepatocellular carcinoma (HCC) remains uncertain. Liver denervation via hepatic vagotomy (HV) significantly reduced liver tumor burden, while pharmacological enhancement of parasympathetic tone promoted tumor growth. Cholinergic disruption in Rag1KO mice revealed that cholinergic regulation requires adaptive immunity. Further scRNA-seq and in vitro studies indicated that vagal ACh dampens CD8+ T cell activity via muscarinic ACh receptor (AChR) CHRM3. Depletion of CD8+ T cells abrogated HV outcomes and selective deletion of Chrm3 on CD8+ T cells inhibited liver tumor growth. Beyond tumor-specific outcomes, vagotomy improved cancer-associated fatigue and anxiety-like behavior. As microbiota transplantation from HCC donors was sufficient to impair behavior, we investigated putative microbiota-neuroimmune crosstalk. Tumor, rather than vagotomy, robustly altered fecal bacterial composition, increasing Desulfovibrionales and Clostridial taxa. Strikingly, in tumor-free mice, vagotomy permitted HCC-associated microbiota to activate hepatic CD8+ T cells. These findings reveal that gut bacteria influence behavior and liver anti-tumor immunity via a dynamic and pharmaceutically targetable, vagus-liver axis.

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Section: Resultsmentioning

confidence: 99%

“…5G and fig. s13F), ( 17 , 51 ). Cholinergic vagal activity maintains liver immune tolerance dampening pro-inflammatory and cytotoxic T cell responses.…”

Section: Resultsmentioning

confidence: 99%

Section: Vagotomy Benefits Neurological Function In Hcc Tumor-bearing...mentioning

confidence: 99%

See 1 more Smart Citation

The Gut Microbiome Controls Liver Tumors via the Vagus Nerve

Bauer,

Trehan,

Ruf

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…This crosstalk is achieved by stimulating the hepatic and ventral branches of the VN to carry the signal to the brain, affecting the activity of neurons [ 4 ] and regulating the expression of corticotropin-releasing factor (CRF) in the hypothalamus and brain-derived neurotrophic factor (BDNF) and N -methyl- d -aspartic acid receptor (NMDA) receptors in the cerebral cortex and hippocampus, which are important regulators of HPA axis function [ 43 ]. The development and function execution of microglia, the in situ immune cells of the brain, are also regulated by the host microbiota [ 45 , 46 ]. Microbial compounds and metabolites from intestinal flora, including indole, tryptophan, histamine, SCFAs and TMAO, are important media for communication between the intestinal tract and the brain that are thought to enter the brain through the blood circulation and trigger responses through a variety of mechanisms [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Different gender-derived gut microbiota influence stroke outcomes by mitigating inflammation

Wang

Zhong

Zhu

et al. 2022

J Neuroinflammation

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Background and purpose Stroke is associated with high disability and mortality rates and increases the incidence of organ-related complications. Research has revealed that the outcomes and prognosis of stroke are regulated by the state of the intestinal microbiota. However, the possibility that the manipulation of the intestinal microbiota can alter sex-related stroke outcomes remain unknown. Methods To verify the different effects of microbiota from different sexes on stroke outcomes, we performed mouse fecal microbiota transplantation (FMT) and established a model of ischemic stroke. Male and female mice received either male or female microbiota through FMT. Ischemic stroke was triggered by MCAO (middle cerebral artery occlusion), and sham surgery served as a control. Over the next few weeks, the mice underwent neurological evaluation and metabolite and inflammatory level detection, and we collected fecal samples for 16S ribosomal RNA analysis. Results We found that when the female mice were not treated with FMT, the microbiota (especially the Firmicutes-to-Bacteroidetes ratio) and the levels of three main metabolites tended to resemble those of male mice after experimental stroke, indicating that stroke can induce an ecological imbalance in the biological community. Through intragastric administration, the gut microbiota of male and female mice was altered to resemble that of the other sex. In general, in female mice after MCAO, the survival rate was increased, the infarct area was reduced, behavioral test performance was improved, the release of beneficial metabolites was promoted and the level of inflammation was mitigated. In contrast, mice that received male microbiota were much more hampered in terms of protection against brain damage and the recovery of neurological function. Conclusion A female-like biological community reduces the level of systemic proinflammatory cytokines after ischemic stroke. Poor stroke outcomes can be positively modulated following supplementation with female gut microbiota.

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“…Microglia are non-neuronal cells. The maturation and function of microglia are influenced by host intestinal microbes [46]. When the GM decrease, microglia develop defects and cannot mature [47].…”

Section: Microglia and Admentioning

confidence: 99%

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

Yin¹,

Xu²,

Jin³

et al. 2023

J. Integr. Neurosci.

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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.

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Gut microbes shape microglia and cognitive function during malnutrition

Cited by 12 publications

References 119 publications

The Gut Microbiome Controls Liver Tumors via the Vagus Nerve

The Gut Microbiome Controls Liver Tumors via the Vagus Nerve

Different gender-derived gut microbiota influence stroke outcomes by mitigating inflammation

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

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