Oxytocin acts centrally in the brain to improve leaky gut through the vagus nerve and a cannabinoid signaling in rats

Okumura, Toshikatsu; Nozu, Tsukasa; Ishioh, Masatomo; Igarashi, Sho; Funayama, Takuya; Kumei, Shima; Ohhira, Masumi

doi:10.1016/j.physbeh.2022.113914

Cited by 9 publications

(4 citation statements)

References 39 publications

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“…Central oxytocin pathways also may project to the efferent vagal nervous system. In rats, intracisternal oxytocin administration reduces colonic hyperpermeability via the vagal cholinergic pathway 16 . The relationship between oxytocin activity and gastrointestinal symptomatology has not been directly explored in ASD.…”

Section: Introductionmentioning

confidence: 99%

Results of a phase Ib study of SB-121, an investigational probiotic formulation, a randomized controlled trial in participants with autism spectrum disorder

Schmitt

Smith

Pedapati

et al. 2023

Sci Rep

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Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by core impairments in social communication as well as restricted, repetitive patterns of behavior and/or interests. Individuals with ASD, which includes about 2% of the US population, have challenges with activities of daily living and suffer from comorbid medical and mental health concerns. There are no drugs indicated for the core impairments of ASD. As such, there is a significant need for the development of new medication strategies for individuals with ASD. This first-in-human placebo-controlled, double-blind, crossover study investigated the safety (primary objective) and efficacy of oral SB-121, a combination of L. reuteri, Sephadex® (dextran microparticles), and maltose administered once daily for 28 days in 15 autistic participants. SB-121 was safe and well tolerated. SB-121-associated directional improvements in adaptive behavior measured by Vineland-3 and social preference as measured with eye tracking were noted. These results provide support for further clinical evaluation of SB-121 as a treatment in autistic patients. To evaluate the safety and tolerability of multiple doses of SB-121 in subjects with autism spectrum disorder. Single-center, randomized, placebo-controlled, double-blind, crossover trial. 15 patients with autism spectrum disorder were randomized and analyzed. Daily dosing of SB-121 or placebo for 28 days, followed by approximately a 14 day washout, then 28 days of dosing with other treatment. Incidence and severity of adverse events, presence of Limosilactobacillus reuteri and Sephadex® in stool, and incidence of bacteremia with positive L. reuteri identification. Additional outcomes include changes from baseline on cognitive and behavior tests as well as biomarker levels. Adverse event rates were similar between SB-121 and placebo, with most reported as mild. There were no severe or serious adverse events. No participants had features of suspected bacteremia or notable changes in vital signs, safety laboratory, or ECG parameters from baseline. There was a statistically significant increase from baseline in the Vineland-3 Adaptive Behavior Composite score (p = 0.03) during SB-121 treatment. There was a trend for increased social/geometric viewing ratio following SB-121 treatment compared to placebo. SB-121 was safe and well tolerated. SB-121-associated directional improvements in adaptive behavior measured by Vineland-3 and social preference as measured with eye tracking were noted.Trial registration: clinicaltrials.gov Identifier: NCT04944901.

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Section: Introductionmentioning

confidence: 99%

Results of a phase Ib study of SB-121, an investigational probiotic formulation, a randomized controlled trial in participants with autism spectrum disorder

Schmitt

Smith

Pedapati

et al. 2023

Sci Rep

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“…For example, one recent experimental study with rats observed that intracisternal injection of oxytocin decreased microbial translocation because of LPS in a dose-dependent manner. Interestingly, these effects of oxytocin on decreased microbial translocation were blocked by vagotomy, which underscores the central importance of efferent vagal communication with the gut (152). There is also experimental evidence in rats that oxytocin could mitigate the effects of stress on gastric emptying and motility (153).…”

Section: Neuroendocrine Signaling and The Microbiome-gut-brain Axismentioning

confidence: 93%

Through the Looking-Glass: Psychoneuroimmunology and the Microbiome-Gut-Brain Axis in the Modern Antiretroviral Therapy Era

et al. 2022

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Objective: Depression, substance use disorders, and other neuropsychiatric comorbidities are common in people with HIV (PWH), but the underlying mechanisms are not sufficiently understood. HIV-induced damage to the gastrointestinal tract potentiates residual immune dysregulation in PWH receiving effective antiretroviral therapy. However, few studies among PWH have examined the relevance of microbiomegut-brain axis: bidirectional crosstalk between the gastrointestinal tract, immune system, and central nervous system. Methods: A narrative review was conducted to integrate findings from 159 articles relevant to psychoneuroimmunology (PNI) and microbiome-gut-brain axis research in PWH. Results: Early PNI studies demonstrated that neuroendocrine signaling via the hypothalamic-pituitary-adrenal axis and autonomic nervous system could partially account for the associations of psychological factors with clinical HIV progression. This review highlights the need for PNI studies examining the mechanistic relevance of the gut microbiota for residual immune dysregulation, tryptophan catabolism, and oxytocin release as key biological determinants of neuropsychiatric comorbidities in PWH (i.e., body-to-mind pathways). It also underscores the continued relevance of neuroendocrine signaling via the hypothalamic-pituitary-adrenal axis, autonomic nervous system, and oxytocin release in modifying microbiome-gut-brain axis functioning (i.e., mind-to-body pathways). Conclusions: Advancing our understanding of PNI and microbiome-gut-brain axis pathways relevant to depression, substance use disorders, and other neuropsychiatric comorbidities in PWH can guide the development of novel biobehavioral interventions to optimize health outcomes. Recommendations are provided for biobehavioral and neurobehavioral research investigating bidirectional PNI and microbiomegut-brain axis pathways among PWH in the modern antiretroviral therapy era.

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“…1A). The results also suggest that the brain indeed plays a vital role in regulation of intestinal barrier function [1, 2, 4]. The improvement of leaky gut by neuropeptides such as orexin, ghrelin, or oxytocin was prevented by atropine or surgical vagotomy, suggesting that the vagal cholinergic pathway mediates the action.…”

Section: Leaky Gut and Visceral Sensation Regulated By Brain Neuropep...mentioning

confidence: 98%

“…Previous studies have revealed that visceral hypersensitivity and intestinal barrier dysfunction are the main pathophysiology of IBS. Since brain-gut axis is considered to be an important factor in IBS, we have examined roles of the brain in the regulation of visceral sensation and intestinal barrier function and have shown that the central nervous system (CNS) regulates visceral sensation in response to colonic distension and intestinal barrier function [1][2][3][4]. Based on the findings, we have speculated that impairment of central regulation of visceral sensation and intestinal barrier function may lead to visceral hypersensitivity and leaky gut, which are the main causes of IBS.…”

Section: Introductionmentioning

confidence: 99%

Brain Neuropeptides, Neuroinflammation, and Irritable Bowel Syndrome

Ishioh,

Nozu,

Okumura

2023

Digestion

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Background: Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by chronic abdominal symptoms, but its pathogenesis is not fully understood. Summary: We have recently shown in rats that neuropeptides such as orexin, ghrelin, and oxytocin act in the brain to improve the intestinal barrier dysfunction, which is a major pathophysiology of IBS. We have additionally shown that the neuropeptides injected intracisternally induced a visceral antinociceptive action against colonic distension. Since it has been known that intestinal barrier dysfunction causes visceral hypersensitivity, the other main pathophysiology of IBS, the neuropeptides act centrally to reduce leaky gut, followed by improvement of visceral sensation, leading to therapeutic action on IBS. It has been recently reported that there is a bidirectional relationship between neuroinflammation in the brain and the pathophysiology of IBS. For example, activation of microglia in the brain causes visceral hypersensitivity. Accumulating evidence has suggested that orexin, ghrelin, or oxytocin could improve neuroinflammation in the CNS. All these results suggest that neuropeptides such as orexin, ghrelin, and oxytocin act in the brain to improve intestinal barrier function and visceral sensation and also induce a protective action against neuroinflammation in the brain. Key Messages: We therefore speculated that orexin, ghrelin, or oxytocin in the brain possess dual actions, improvement of visceral sensation/leaky gut in the gut, and reduction of neuroinflammation in the brain, thereby inducing a therapeutic effect on IBS in a convergent manner.

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Oxytocin acts centrally in the brain to improve leaky gut through the vagus nerve and a cannabinoid signaling in rats

Cited by 9 publications

References 39 publications

Results of a phase Ib study of SB-121, an investigational probiotic formulation, a randomized controlled trial in participants with autism spectrum disorder

Results of a phase Ib study of SB-121, an investigational probiotic formulation, a randomized controlled trial in participants with autism spectrum disorder

Through the Looking-Glass: Psychoneuroimmunology and the Microbiome-Gut-Brain Axis in the Modern Antiretroviral Therapy Era

Brain Neuropeptides, Neuroinflammation, and Irritable Bowel Syndrome

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