Sex differences feed into nuclear receptor signaling along the digestive tract

Dean, Angela E.; Reichardt, François; Anakk, Sayeepriyadarshini

doi:10.1016/j.bbadis.2021.166211

Cited by 6 publications

(5 citation statements)

References 206 publications

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“…Numerous sex‐related differences in GI physiology are recognized in clinical and preclinical models and females are known to have a higher prevalence of GI‐related disorders overall 58–60 . Despite these known differences, the influence of sex on enteric nervous system anatomy and function has been inconsistently studied, or not clearly isolated in mixed‐sex studies.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous sex-related differences in GI physiology are recognized in clinical and preclinical models and females are known to have a higher prevalence of GI-related disorders overall. [58][59][60] Despite these known differences, the influence of sex on enteric nervous system anatomy and function has been inconsistently studied, or not clearly isolated in mixed-sex studies. Additionally, steroid hormone receptors have been identified throughout the GI tract, which may have effects independent of CNS neurons that are typically thought to govern GI reflexes.…”

Section: Sex Differences Impacting the Regulation Of Iccmentioning

confidence: 99%

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Plasticity of colonic enteric nervous system following spinal cord injury in male and female rats

Werner

Willing

Goudsward

et al. 2023

Neurogastroenterology Motil

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BackgroundNeurogenic bowel is a dysmotility disorder following spinal cord injury (SCI) that negatively impacts quality of life, social integration, and physical health. Colonic transit is directly modulated by the enteric nervous system. Interstitial Cells of Cajal (ICC) distributed throughout the small intestine and colon serve as specialized pacemaker cells, generating rhythmic electrical slow waves within intestinal smooth muscle, or serve as an interface between smooth muscle cells and enteric motor neurons of the myenteric plexus. Interstitial Cells of Cajal loss has been reported for other preclinical models of dysmotility, and our previous experimental SCI study provided evidence of reduced excitatory and inhibitory enteric neuronal count and smooth muscle neural control.MethodsImmunohistochemistry for the ICC‐specific marker c‐Kit was utilized to examine neuromuscular remodeling of the distal colon in male and female rats with experimental SCI.Key ResultsMyenteric plexus ICC (ICC‐MP) exhibited increased cell counts 3 days following SCI in male rats, but did not significantly increase in females until 3 weeks after SCI. On average, ICC‐MP total primary arborization length increased significantly in male rats at 3‐day, 3‐week, and 6‐week time points, whereas in females, this increase occurred most frequently at 6 weeks post‐SCI. Conversely, circular muscle ICC (ICC‐CM) did not demonstrate post‐SCI changes.Conclusions and InferencesThese data demonstrate resiliency of the ICC‐MP in neurogenic bowel following SCI, unlike seen in other related disease states. This plasticity underscores the need to further understand neuromuscular changes driving colonic dysmotility after SCI in order to advance therapeutic targets for neurogenic bowel treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Sex Differences Impacting the Regulation Of Iccmentioning

confidence: 99%

Plasticity of colonic enteric nervous system following spinal cord injury in male and female rats

Werner

Willing

Goudsward

et al. 2023

Neurogastroenterology Motil

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show abstract

“…The physiological differences between men and women are still unclear, but depending on the gender, the differences can be seen in the nuclear receptors that control many functional pathways in the alimentary canal. These differences can also be seen in the body's capacity to secrete the right hormones in response to the nutrition received, where the nuclear receptors have an impact on metabolism [26]. H. Gilliam-Vigh et al [27] found no discernible difference between diabetes patients and healthy controls in the density of CCK cells and CCK mRNA in the small intestine and at a lower level in the large intestine.…”

Section: Discussionmentioning

confidence: 99%

Estimation levels of cholecystokinin, gastrin and secretin in patients with type 2 diabetes mellitus

Al-Akabi

2022

basjs

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A diabetic patient with diabetes mellitus experiences high blood sugar levels as a result of low insulin levels or resistance to the medication's effects. The tests were carried out at a medical laboratory using specialized kits, and the 45 patient samples and 45 healthy person samples from both sexes as a control group were dispersed based on the questionnaire form. In contrast to the non-significant rise in serum gastrin and secretin levels, the results demonstrated a substantial increase in cholecystokinin (CCK) levels between the patient and control groups and a significant increase in CCK levels according to gender, type of therapy, and disease history. In conclusion, individuals with diabetes mellitus type 2 may have aberrant blood CCK levels, which require concentration to assess the full scope of their impact on the individual.

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“…Biological sex and the reproductive axis are fundamental to mammalian development and physiology. In addition to controlling sexual differentiation, fertility, and sex steroid production, the reproductive axis influences the nervous, musculoskeletal, cardiovascular, immune, hepatic, and gastrointestinal systems [1][2][3][4][5][6][7]. Additionally, many diseases have a sex bias, including autoimmune disorders such as lupus, Crohn's disease, and ulcerative colitis [8,9], or are influenced by sex steroids, such as polycystic ovary syndrome and cardiovascular disease [5,10].…”

Section: Introductionmentioning

confidence: 99%

Genetic hypogonadal mouse model reveals niche-specific influence of reproductive axis and sex on intestinal microbial communities

Sisk-Hackworth,

Brown,

et al. 2023

Biol Sex Differ

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Background The gut microbiome has been linked to many diseases with sex bias including autoimmune, metabolic, neurological, and reproductive disorders. While numerous studies report sex differences in fecal microbial communities, the role of the reproductive axis in this differentiation is unclear and it is unknown how sex differentiation affects microbial diversity in specific regions of the small and large intestine. Methods We used a genetic hypogonadal mouse model that does not produce sex steroids or go through puberty to investigate how sex and the reproductive axis impact bacterial diversity within the intestine. Using 16S rRNA gene sequencing, we analyzed alpha and beta diversity and taxonomic composition of fecal and intestinal communities from the lumen and mucosa of the duodenum, ileum, and cecum from adult female (n = 20) and male (n = 20) wild-type mice and female (n = 17) and male (n = 20) hypogonadal mice. Results Both sex and reproductive axis inactivation altered bacterial composition in an intestinal section and niche-specific manner. Hypogonadism was significantly associated with bacteria from the Bacteroidaceae,Eggerthellaceae,Muribaculaceae, and Rikenellaceae families, which have genes for bile acid metabolism and mucin degradation. Microbial balances between males and females and between hypogonadal and wild-type mice were also intestinal section-specific. In addition, we identified 3 bacterial genera (EscherichiaShigella, Lachnoclostridium, and Eggerthellaceaegenus) with higher abundance in wild-type female mice throughout the intestinal tract compared to both wild-type male and hypogonadal female mice, indicating that activation of the reproductive axis leads to female-specific differentiation of the gut microbiome. Our results also implicated factors independent of the reproductive axis (i.e., sex chromosomes) in shaping sex differences in intestinal communities. Additionally, our detailed profile of intestinal communities showed that fecal samples do not reflect bacterial diversity in the small intestine. Conclusions Our results indicate that sex differences in the gut microbiome are intestinal niche-specific and that sampling feces or the large intestine may miss significant sex effects in the small intestine. These results strongly support the need to consider both sex and reproductive status when studying the gut microbiome and while developing microbial-based therapies.

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Sex differences feed into nuclear receptor signaling along the digestive tract

Cited by 6 publications

References 206 publications

Plasticity of colonic enteric nervous system following spinal cord injury in male and female rats

Plasticity of colonic enteric nervous system following spinal cord injury in male and female rats

Estimation levels of cholecystokinin, gastrin and secretin in patients with type 2 diabetes mellitus

Genetic hypogonadal mouse model reveals niche-specific influence of reproductive axis and sex on intestinal microbial communities

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