Gut-brain axis targeting postbiotics for treatment of psychological and neurodegenerative disorders

 

There is massive amounts of research on this already! What's needed IS EXACT PROTOCOLS TO GET SURVIVORS RECOVERED! And you are too blitheringly stupid to see what needs to be done!

• gut-brain axis(45 posts to January 2016)
• gut microbiome (63 posts to March 2016)
• gut microbiota (45 posts to June 2016)

Gut-brain axis targeting postbiotics for treatment of psychological and neurodegenerative disorders

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Highlights

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  Postbiotics offer a therapeutic option as an adjuvant or alternative therapy.
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  Stringent manufacturing, handling and storage requirements plaguing probiotics are circumvented by postbiotics.
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  Postbiotics can alter neurogenetics and trigger meaningful changes to psychological and neurodegenerative pathways.
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  Stress hormonal responses are altered by postbiotics, mitigating pathogenesis of anxiety and depression.

Abstract

Current pharmacological treatments for psychological and neurodegenerative disorders largely ignore the vital role of the gut microbiome in cognition. Antipsychotics and antidepressants often disturb the gut environment, impacting mood stabilisation, neurotransmitter signalling, and cognitive functions mediated by the gut-brain axis. This ultimately undermines treatment efficacy while triggering cascading metabolic side effects, including weight gain and hyperglycaemia. Coupled with the rising global burden of these disorders, there is a need for innovative therapies that effectively target the gut microbiome to pharmacologically mediate the gut-brain axis. Postbiotics, comprising inert microorganisms or their components, are one such microbiome-targeted therapy that has recently shown the capacity to treat an array of psychological and neurodegenerative disorders, including depression, anxiety, Alzheimer's, and Parkinson's disease, while mitigating common manufacturing, storage, and efficacy limitations of conventional probiotics. However, clinical trials validating postbiotic treatment efficacy in neurological diseases are lacking, indicating the need for further investigation. This review therefore aims to examine the therapeutic potential of postbiotics and bridge the gap between preclinical research and clinical practice.

Graphical abstract

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Targeting the microbiota-gut-brain axis in post-stroke insomnia: a phase-dependent therapeutic framework

 Wonderful descriptions; but complete failure at producing anything for stroke recovery!

Targeting the microbiota-gut-brain axis in post-stroke insomnia: a phase-dependent therapeutic framework

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  Yumin Zhou

• Y

  Yingying Huang

• 

  Xia Bi *

• Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, China

Abstract

Post-stroke insomnia (PSI) is a critical biological barrier to neurorehabilitation afflicting over half of all stroke survivors. Traditional sedatives often force clinicians into a therapeutic dilemma between sleep efficacy and cognitive suppression. The microbiota-gut-brain (MGB) axis has recently emerged as a transformative target to resolve this impasse. Acute stroke triggers profound autonomic dysfunction, causing immediate intestinal barrier collapse. This “leaky gut” facilitates the systemic translocation of lipopolysaccharides (LPS) and activates the NLRP3 inflammasome. The resulting inflammatory storm hijacks central tryptophan metabolism via the indoleamine 2,3-dioxygenase (IDO) enzyme. This “tryptophan steal” diverts serotonin precursors toward neurotoxic kynurenine pathways, driving severe cortical hyperarousal. Sleep fragmentation then prevents the glymphatic system from clearing metabolic waste, further exacerbating neuroinflammation. To break this vicious cycle of neurotoxicity, we propose a phase-dependent therapeutic framework. During the highly vulnerable acute phase, interventions must prioritize gut barrier protection using postbiotics to mitigate infection risks under CNS injury-induced immunodepression (CIDS), often discussed as stroke-induced immunosuppression. As patients enter the chronic phase, therapy shifts toward metabolic restoration using live therapeutics, such as washed microbiota transplantation (WMT) and next-generation psychobiotics like Akkermansia muciniphila. Targeting the MGB axis offers a mechanism-based strategy to achieve precision sleep medicine, restoring the biological foundation necessary for optimal neuroplasticity and recovery.

1 Introduction

1.1 The silent epidemic: beyond symptomology

Stroke remains a formidable global health challenge, consistently ranking among the leading causes of mortality and long-term adult disability worldwide (GBD 2019 Stroke Collaborators, 2021; Feigin et al., 2025). While the advent of hyper-acute recanalization therapies—such as mechanical thrombectomy and intravenous thrombolysis—has improved acute outcomes, these advances have coincided with a growing population of survivors living with chronic sequelae (GBD 2019 Stroke Collaborators, 2021; Feigin et al., 2025). Among these, sleep–wake disturbances are pervasive yet frequently underestimated in routine clinical practice, often overshadowed by more visible motor deficits (Khot and Morgenstern, 2019). Epidemiological evidence suggests that sleep problems affect roughly half of stroke survivors, consistent with pooled estimates of poor sleep quality after stroke and broader post-stroke sleep-disorder burden (Khot and Morgenstern, 2019; Luo et al., 2023). Of these disorders, post-stroke insomnia (PSI) is commonly reported and can persist, presenting a barrier to effective neurorehabilitation (Wang et al., 2024; Sun et al., 2026). PSI is characterized not merely by difficulties in sleep initiation, but also by fragmentation of sleep continuity and non-restorative rest (Wang et al., 2024). The clinical ramifications of untreated PSI extend beyond subjective fatigue or daytime somnolence; disrupted sleep after stroke has been associated with poorer functional outcomes and increased risk of adverse vascular events in observational and review evidence (Khot and Morgenstern, 2019). Sleep is a fundamental physiological pillar for neuroplasticity and memory consolidation, and sleep disruption may therefore hinder recovery processes after stroke (Khot and Morgenstern, 2019). Indeed, disrupted sleep in the post-stroke period has been linked to worse functional recovery and mood and cognitive outcomes, supporting proactive recognition and targeted management rather than passive observation.

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Brain-gut communication and potential applications of microecological treatments in stroke

 There is massive amounts of research on this already! What's needed IS EXACT PROTOCOLS TO GET SURVIVORS RECOVERED! And you are too blitheringly stupid to see what needs to be done!

• gut-brain axis(45 posts to January 2016)
• gut microbiome (63 posts to March 2016)
• gut microbiota (45 posts to June 2016)

Brain-gut communication and potential applications of microecological treatments in stroke

• 

  Mingzhu Gao 1†

• 

  Yujie Zhou 1†

• 

  Kaixin Zhang 1

• Y

  Yang Ye 2

• Z

  Zhijun Han 1

• 

  Qi Chen 1‡ *

• 

  Wentao Shi 3‡ *

• X

  Xiaojie Lu 3‡ *

• 1. Department of Clinical Research Center, Jiangnan University Medical Center (Wuxi No.2 People’s Hospital), Wuxi School of Medicine, Jiangnan University, Wuxi, China

• 2. Research Institute for Reproductive Health and Genetic Diseases, Wuxi Maternity and Child Health Care Hospital, Wuxi School of Medicine, Jiangnan University, Wuxi, China

Abstract

Stroke is a cerebrovascular disease with high incidence rates, serious disability and increased mortality rates, thereby posing a serious threat to human health. The mechanisms of brain-gut communication have gradually emerged in recent times. This article focuses on the gut-brain axis and discusses the bidirectional regulatory pathways between gut microecology and stroke via the neurotransmitter, colony metabolite, endocrine, and immunoregulatory pathways. Additionally, it summarizes the latest applications of gut microecological agents in stroke, which may provide new research ideas and clinical treatment strategies for the microecological diagnosis and therapy of stroke.

1 Introduction

As one of the leading causes of mortality and lifelong disability globally, stroke imposes significant economic, social and clinical burdens on patients, families and health services (GBD 2019 Stroke Collaborators, 2021; Kim et al., 2020). Particularly in low and middle income countries, stroke incidence continues to increase as a result of progressive global population aging and rise in the prevalence of cardiovascular risk factors, namely obesity, dyslipidemia, hypertension and diabetes mellitus (O'Donnell et al., 2016; Vaduganathan et al., 2022). The functional recovery post-stroke is often incomplete since there are limited effective treatment options for the condition despite advances in acute reperfusion therapies, such as mechanical thrombectomy and thrombolysis (Campbell and Khatri, 2020). To improve prevention, treatment and prognosis of stroke, identification of novel pathophysiological mechanisms and pharmacological targets are increasing demanded.

The role of gut microbiota in causing neurological diseases has gained increased attention in recent times. Gut microbiota collectively refers to a complex and dynamic microbial system, which is harbored in the human and is composed of archaea, fungi, viruses and bacteria (Sender et al., 2016). In view of their huge genetic repertoire, these microorganisms have been found to participate in physiological processes, such as maintenance of intestinal barrier integrity, maturation of immune system, protection against pathogenic invasion, synthesis of vitamins, and metabolism of nutrients (Sommer and Bäckhed, 2013; Round and Mazmanian, 2009). Various diseases such as cardiovascular diseases (CVDs), central nervous system (CNS) disorders, immune-mediated conditions and metabolic disorders developed as a result of dysbiosis (imbalance of gut microbiome) (Lynch and Pedersen, 2016; Tilg et al., 2020).

The gastrointestinal tract (GIT) is linked to the CNS by a two-way directional communication network known as gut-brain axis (GBA) via immune, metabolic and neural pathways (Cryan and Dinan, 2012). The development, function and behavior of the brain can be influenced by gut microbiota through this axis with the brain modulating the mobility, secretion, permeability and immune responses of the gut (Carabotti et al., 2015). Growing evidence suggests that the potential for gut microbiota-derived hormones, inflammatory mediators, neurotransmitters and metabolites to cross the barrier of intestines and occasionally the blood–brain barrier (BBB) can directly or indirectly affect neuroinflammatory processes and neuronal activity (Sharon et al., 2016; Fung et al., 2017). Acute brain injuries including stroke, neuropsychiatric conditions and neurogenerative disorders have been linked with GBA dysregulation (Sampson and Mazmanian, 2015; Dinan and Cryan, 2020; Góralczyk-Bińkowska et al., 2022).

Through emerging studies, scientists have discovered stroke as a systemic disease and focal cerebrovascular event that significantly impact function of gut and composition of microbiome (Chidambaram et al., 2022; Szegedi et al., 2025). Also, secondary brain function, systemic inflammation and immune dysfunction were exacerbated by acute cerebral ischemia or hemorrhage-induced intestinal dysmotility, increased permeability of gut and microbiota dysbiosis (Singh et al., 2016; Winek et al., 2016). In contrast, susceptibility and recovery of stroke, infarct size, and inflammation after stroke are influenced by pre-existing composition of gut microbiota and their metabolites (Benakis et al., 2016; Yamashiro et al., 2017). Based on available evidence, gut microbiota can be considered as a contributor to pathogenesis of stroke and as a potential target for treatment of the condition.

In this context, scientists have given much attention to microecological agents (MEAs), namely microbiota-derived metabolites, synbiotics, prebiotics and probiotics, which have been regarded as adjunctive schemes for prevention, treatment and rehabilitation of stroke (Zhong et al., 2021; Li et al., 2023). It is evidenced that the aforementioned interventions may regulate metabolic pathways, reduce neuroinflammation, ameliorate homeostasis of immune system and promote post-stroke recovery of neurons by modulating of composition and function of gut microbiome (Sadler et al., 2020). Nevertheless, scientists have not clearly understood the mechanisms that underlie interaction of microbiota–brain in stroke, while further systematic evaluation of clinical translation of microbiome-based therapies is required.

This article explores four major regulatory pathways and mechanisms involved in brain-gut communication based on the concept of the GBA (Figure 1). It also summarizes the cutting-edge applications of MEAs in the diagnosis and treatment of stroke (Table 1), thus providing new research ideas and clinical treatment approaches for microecological diagnosis and stroke treatment.

Four major regulatory pathways of brain-gut dialogues.

Table 1