You’ve got male: Sex and the microbiota-gut-brain axis across the lifespan

Jaggar, Minal; Rea, Kieran; Spichak, Simon; Dinan, Timothy G.; Cryan, John F.

doi:10.1016/j.yfrne.2019.100815

Cited by 150 publications

(109 citation statements)

References 317 publications

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“…It is worth pointing out that for the majority of our studies of microbiota to brain interactions the effects are much more robust in males 94 . However, much research is still needed to unravel this interaction, and recent evidence suggests that besides the sex bias for mental disorders, an interaction between the sex, sex hormones and the gut microbiota is highly possible with the gut microbiota 94 . Future studies will determine how sex and sex hormones determine discrete genes changes in the amygdala as well in the gut.…”

Section: Discussionmentioning

confidence: 97%

Enduring neurobehavioral effects induced by microbiota depletion during the adolescent period

et al. 2020

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The gut microbiota is an essential regulator of many aspects of host physiology. Disruption of gut microbial communities affects gut-brain communication which ultimately can manifest as changes in brain function and behaviour. Transient changes in gut microbial composition can be induced by various intrinsic and extrinsic factors, however, it is possible that enduring shifts in the microbiota composition can be achieved by perturbation at a timepoint when the gut microbiota has not fully matured or is generally unstable, such as during early life or ageing. In this study, we investigated the effects of 3-week microbiota depletion with antibiotic treatment during the adolescent period and in adulthood. Following a washout period to restore the gut microbiota, behavioural and molecular hallmarks of gut-brain communication were investigated. Our data revealed that transient microbiota depletion had long-lasting effects on microbiota composition and increased anxiety-like behaviour in mice exposed to antibiotic treatment during adolescence but not in adulthood. Similarly, gene expression in the amygdala was more severely affected in mice treated during adolescence. Taken together these data highlight the vulnerability of the gut microbiota during the critical adolescent period and the long-lasting impact manipulations of the microbiota can have on gene expression and behaviour in adulthood.

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Section: Discussionmentioning

confidence: 97%

Enduring neurobehavioral effects induced by microbiota depletion during the adolescent period

et al. 2020

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“…Sex differences in susceptibility to anxiety, mood, and other neuropsychiatric disorders has been established in humans (99)(100)(101)(102). Therefore, the influence that mPFC physiology and function has on behavior in both males and females has significant translational value for identifying both susceptibility and treatment options.…”

Section: Pl Pyr Girk1 Knockout and Cus Exposure In Femalesmentioning

confidence: 99%

Suppression of pyramidal neuron G protein-gated inwardly rectifying K+ channel signaling impairs prelimbic cortical function and underlies stress-induced deficits in cognitive flexibility

Anderson

Loke

Wrucke

et al. 2020

Preprint

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wordsMain Text: 4252 words Abstract Background: Imbalance in prefrontal cortical (PFC) pyramidal neuron excitation:inhibition is thought to underlie symptomologies shared across stress-related disorders and neuropsychiatric disease, including dysregulation of emotion and cognitive function. G protein-gated inwardly rectifying K + (GIRK/Kir3) channels mediate excitability of medial PFC pyramidal neurons, however the functional role of these channels in mPFC-dependent regulation of affect, cognition, and cortical dynamics is unknown. Methods:In mice harboring a 'floxed' version of the kcnj3 (Girk1) gene, we used a viral-cre approach to disrupt GIRK1-containing channel expression in pyramidal neurons within the prelimbic (PL) or infralimbic (IL) cortices. Additional studies used a novel model of chronic unpredictable stress (CUS) to determine the impact on PL GIRK-dependent signaling and cognitive function. Results:In males, loss of pyramidal GIRK-dependent signaling in the PL, but not IL, differentially impacted measures of affect and motivation, and impaired working memory and cognitive flexibility. CUS produced similar deficits in affect and cognition that paralleled a reduction in PL pyramidal GIRK-dependent signaling akin to viral approaches. Viral-and stress-induced behavioral deficits were rescued by systemic injection of a novel, GIRK1-selective agonist, ML-297. Unexpectedly, neither ablation of PL GIRK-dependent signaling or exposure to the CUS regimen impacted affect or cognition in female mice.Conclusions: GIRK-dependent signaling in male mice, but not females, is critical for maintaining optimal PL function and behavioral control. Disruption of this inhibition may underlie stress-related dysfunction of the PL and represent a therapeutic target for treating stress-induced deficits in affect regulation and impaired cognition that reduce quality of life.

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“…Nevertheless, there are inconclusive reports of benefits of antidepressant medications for treatment of recurrent abdominal pain in children and adolescents 35 . Sex-differences in the gut microbiome through the life-course have been associated with mental health disorders, including anxiety and depression 36,37 , as well as with functional gastrointestinal disorders 38 . Consequently, influences of the gut microbiome on the gut-brain axis may contribute to the link between abdominal pain and the mental health of adolescents.…”

Section: Discussionmentioning

confidence: 99%

The relationship between abdominal pain and emotional wellbeing in children and adolescents in the Raine Study

Ayonrinde

Adams

et al. 2020

Sci Rep

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Abdominal pain is a common reason for medical visits. We examined the prevalence, gastrointestinal, and emotional significance of abdominal pain in a population-based cohort serially followed up from birth to 17 years. Children and adolescents from Generation 2 of the Raine Study participated in comprehensive cross-sectional assessments at ages 2, 5, 8, 10, 14 and 17 years. At 17 years, medical history, general health, gastrointestinal symptoms, medications, health practitioner attendance, and self-rated unhappiness were recorded. Longitudinal data regarding abdominal pain or unhappiness, from serial questionnaires, were analysed to identify factors associated with abdominal pain and adverse emotional health at age 17 years. Females experienced more abdominal pain than males at all ages (p < 0.05). Seventeen-year-old adolescents with abdominal pain reported a higher prevalence of depression, anxiety, being bullied at school, and poorer health status than those without abdominal pain (p < 0.05 for all). Abdominal pain and unhappiness during childhood and mid-adolescence were prospectively associated with recurrent abdominal pain, anxiety, depression and unhappiness during late adolescence (p < 0.05 for all). In conclusion, abdominal pain in children and adolescents associates with depression, anxiety, being bullied, unhappiness and reduced overall health-rating during adolescence. Awareness of these factors may guide management decisions.Abdominal pain is one of the most common reasons for primary care, hospital outpatients or emergency department visits, hospitalisations, referrals to gastroenterologists and for imaging tests 1-7 . In 2016/2017, abdominal and pelvic pain was the most common principal diagnosis for emergency department presentations and hospitalisations in Australia, accounting for 4.3% of principal diagnoses 8 . Likewise, in the USA in 2014/2015, abdominal pain was the most frequent reason for gastrointestinal-related ambulatory medical visits to primary care and emergency departments, with an expenditure of US$10.2 billion 2 . In Australia, abdominal pain accounted for 2.1 per 100 patient primary care visits, and the aetiology was not confirmed in one third of males and half of females 9 . Only one third of patients were prescribed medications, primarily paracetamol or hyoscine butylbromide for the pain, while counselling was the most common non-pharmacological treatment. This suggests a suspected diagnosis of a functional abdominal pain disorder 10 . Rome IV diagnostic criteria for functional gastrointestinal disorders describe four main categories of functional abdominal pain disorders in children and adolescents. These comprise functional dyspepsia, irritable bowel syndrome, abdominal migraine and functional abdominal pain -not otherwise specified, which can coexist with each other and with other medical conditions associating with gastrointestinal symptoms in the same individual 11 .

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You’ve got male: Sex and the microbiota-gut-brain axis across the lifespan

Cited by 150 publications

References 317 publications

Enduring neurobehavioral effects induced by microbiota depletion during the adolescent period

Enduring neurobehavioral effects induced by microbiota depletion during the adolescent period

Suppression of pyramidal neuron G protein-gated inwardly rectifying K+ channel signaling impairs prelimbic cortical function and underlies stress-induced deficits in cognitive flexibility

The relationship between abdominal pain and emotional wellbeing in children and adolescents in the Raine Study

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