Sex and age dimorphism of the gut-brain axis in ischemic stroke: A systematic review of preliminary studies

Guido, Giorgio; Crivellaro, Elisa; Fortunato, Giulia De; Melloni, Lorenzo

doi:10.1016/j.brainres.2022.147888

Cited by 6 publications

(3 citation statements)

References 52 publications

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“…Usually, the F/B ratio increases with age and is regarded as an hallmark of gut dysbiosis, with a higher F/B ratio implying a more disordered microbiota composition [ 39 ]. Our finding is comparable to data reported in numerous studies [ 40 – 42 ] that concluded that sex alters the intestinal flora in mice and humans. When comparing fecal samples from male and female mice of the same age, we found a clear sex difference at the phylum level and a significantly higher F/B ratio in male mice.…”

Section: Discussionsupporting

confidence: 92%

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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Section: Discussionsupporting

confidence: 92%

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

Wang

Zhong

Zhu

et al. 2022

J Neuroinflammation

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“…According to the AMSTAR-2 criteria, 21 SRs [7,[17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] scored "critically low," 16 SR [13,[37][38][39][40][41][42][43][44][45][46][47][48][49][50][51] scored "low," and 5 SR [36,[52][53][54][55] scored "moderate" (Figure 2). The most frequent drawbacks were as follows: no mentioning of the protocol in the systematic overview, no description of the rationale for the study designs included in the review, and no statement of funding for the included studies.…”

Section: Methodological Quality Of Included Studiesmentioning

confidence: 99%

The Role of Gut Microbiota in Various Neurological and Psychiatric Disorders—An Evidence Mapping Based on Quantified Evidence

Zang

Lai

et al. 2023

Mediators of Inflammation

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Background and Object. There is a growing body of evidence highlighting the significant role of gut microbiota in various neurological and psychiatric disorders. We performed an evidence mapping to review the association between different microbiota and these disorders and assessed the strength of evidence for these associations. Methods. We searched PubMed, Cochrane Library, and Epistemonikos to identify systematic reviews and meta-analysis (SRs). We searched for neurological diseases and psychiatric disorders, including Alzheimer’s disease (AD), attention deficit hyperactivity disorder (ADHD), amyotrophic lateral sclerosis (ALS), autism spectrum disorder (ASD), anorexia nervosa (AN), bipolar disorder (BD), eating disorder (ED), generalized anxiety disorder (GAD), major depressive disorder (MDD), multiple sclerosis (MS), obsessive compulsive disorder (OCD), Parkinson’s disease (PD), posttraumatic stress disorder (PTSD), spinal cord injury (SCI), schizophrenia, and stroke. We used A Measurement Tool to Assess Systematic Reviews (AMSTAR-2) to evaluate the quality of included SRs. We also created an evidence map showing the role of gut microbiota in neurological diseases and the certainty of the evidence. Results. In total, 42 studies were included in this evidence mapping. Most findings were obtained from observational studies. According to the AMSTAR-2 assessment, 21 SRs scored “critically low” in terms of methodological quality, 16 SR scored “low,” and 5 SR scored “moderate.” A total of 15 diseases have been investigated for the potential association between gut microbiome alpha diversity and disease, with the Shannon index and Simpson index being the most widely studied. A total of 12 diseases were investigated for potential link between beta diversity and disease. At the phylum level, Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, and Verrucomicrobia were more researched. At the genus level, Prevotella, Coprococcus, Parabacteroides, Phascolarctobacterium, Escherichia Shigella, Alistipes, Sutteralla, Veillonella, Odoribacter, Faecalibacterium, Bacteroides, Bifidobacterium, Dialister, and Blautia were more researched. Some diseases have been found to have specific flora changes, and some diseases have been found to have common intestinal microbiological changes. Conclusion. We found varied levels of evidence for the associations between gut microbiota and neurological diseases; some gut microbiota increased the risk of neurological diseases, whereas others showed evidence of benefit that gut microbiota might be promising therapeutic targets for such diseases.

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“…For instance, Fusobacterium necrophorum has been identified as a causal factor of Lemierre's syndrome [41], and it has been established that F. nucleatum plays a role in the onset and progression of colorectal cancer [42]. Differences in Fusobacteriaceae and Fusobacterium abundance have also been observed in IS [35, 43, 44]. In a recent study, where 141 participants were classified as high, moderate or low stroke risk depending on the presence of known risk factors and/or any chronic diseases, it was observed that individuals from the high stroke risk group had increased levels of Fusobacterium compared with participants from the low risk group [35].…”

Section: Discussionmentioning

confidence: 99%

Ischaemic stroke patients present sex differences in gut microbiota

Lledós

Prats‐Sánchez

Llucià‐Carol

et al. 2023

Euro J of Neurology

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BackgroundGut microbiota plays a role in the pathophysiology of ischaemic stroke (IS) through the bidirectional gut–brain axis. Nevertheless, little is known about sex‐specific microbiota signatures in IS occurrence.MethodsA total of 89 IS patients and 12 healthy controls were enrolled. We studied the taxonomic differences of the gut microbiota between men and women with IS by shotgun metagenomic sequencing. To evaluate the causal effect of several bacteria on IS risk, we performed a two‐sample Mendelian randomisation (MR) with inverse‐variance weighting (IVW) using genome‐wide association analysis (GWAS) summary statistics from two cohorts of 5959 subjects with genetic and microbiota data and 1,296,908 subjects with genetic and IS data, respectively.Resultsα‐Diversity analysis measured using Observed Species (p = 0.017), Chao1 (p = 0.009) and Abundance‐based Coverage Estimator (p = 0.012) indexes revealed that IS men have a higher species richness compared with IS women. Moreover, we found sex‐differences in IS patients in relation to the phylum Fusobacteria, class Fusobacteriia, order Fusobacteriales and family Fusobacteriaceae (all Bonferroni‐corrected p < 0.001). MR confirmed that increased Fusobacteriaceae levels in the gut are causally associated with an increased risk of IS (IVW p = 0.02, β = 0.32).ConclusionsOur study is the first to indicate that there are gut microbiome differences between men and women with IS, identifying high levels of Fusobacteriaceae in women as a specific risk factor for IS. Incorporating sex stratification analysis is important in the design, analysis and interpretation of studies on stroke and the gut microbiota.

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Sex and age dimorphism of the gut-brain axis in ischemic stroke: A systematic review of preliminary studies

Cited by 6 publications

References 52 publications

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

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

The Role of Gut Microbiota in Various Neurological and Psychiatric Disorders—An Evidence Mapping Based on Quantified Evidence

Ischaemic stroke patients present sex differences in gut microbiota

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