Gastrointestinal and brain barriers: unlocking gates of communication across the microbiota–gut–brain axis

Aburto, María R.; Cryan, John F.

doi:10.1038/s41575-023-00890-0

Cited by 24 publications

(8 citation statements)

References 281 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The gastrointestinal tract operates under a complex network involving central, autonomic, and enteric nervous systems, making it susceptible to influences from adverse emotions and psychological factors ( Aburto and Cryan, 2024 ). This disruption in the brain-gut axis can lead to gastrointestinal dysfunction due to imbalances between the hypothalamus and limbic system, as well as reduced vagal nerve excitability.…”

Section: Discussionmentioning

confidence: 99%

Exploration of the mechanism of Traditional Chinese Medicine for anxiety and depression in patients with diarrheal irritable bowel syndrome based on network pharmacology and meta-analysis

Bai,

Wang,

Wang

et al. 2024

Front. Pharmacol.

View full text Add to dashboard Cite

BackgroundThe efficacy of Chinese herbal medicine (CHM) in managing irritable bowel syndrome with diarrhea (IBS-D) accompanied by anxiety and depression remains uncertain. Thus, a systematic review was carried out employing meta-analysis and network pharmacology to ascertain the efficacy and underlying mechanisms of CHM therapy.MethodsBy conducting a systematic review, including literature search, screening, and data extraction, we identified 25 randomized controlled trials to assess CHM’s effectiveness in treating irritable bowel syndrome alongside anxiety and depression. Network pharmacology was utilized to scrutinize the metabolite utility of CHM in addressing this condition. Potential primary mechanisms were synthesized using information sourced from the PubMed database.ResultsTwenty-five studies, including 2055 patients, were analyzed, revealing significant treatment efficacy for IBS-D in the trial group compared to controls [OR = 4.01, 95% CI (2.99, 5.36), I2 = 0%] Additionally, treatment for depression [SMD = −1.08, 95% CI (-1.30, −0.86), p < 0.00001, I2 = 68%; SDS: SMD = -1.69, 95% CI (-2.48, −0.90), p < 0.0001, I2 = 96%] and anxiety [HAMA: SMD = -1.29, 95% CI (-1.68, −0.91), p < 0.00001, I2 = 89%; SAS: SMD = -1.75, 95% CI (-2.55, −0.95), p < 0.00001, I2 = 96%] significantly improved in the trial group. Furthermore, the trial group exhibited a significantly lower disease relapse rate [OR = 0.30, 95% CI (0.20, 0.44), p < 0.00001, I2 = 0%]. CHM treatment consistently improved IBS severity (IBS-SSS) and symptom scores. Network pharmacology analysis identified key chemical metabolites in traditional Chinese medicine formulations, including Beta-sitosterol, Stigmasterol, Quercetin, Naringenin, Luteolin, Kaempferol, Nobiletin, Wogonin, Formononetin, and Isorhamnetin. Utilizing the STRING database and Cytoscape v3.9.0 software, a protein-protein interaction (PPI) network revealed the top eight key targets: IL-6, TNF, PPARG, PTGS2, ESR1, NOS3, MAPK8, and AKT1, implicated in anti-inflammatory responses, antioxidant stress modulation, and neurotransmitter homeostasis maintenance.ConclusionChinese Herbal Medicine (CHM) offers a promising and safe treatment approach for patients dealing with Diarrheal Irritable Bowel Syndrome (IBS-D) accompanied by anxiety and depression; thus, indicating its potential for practical implementation. The most active metabolites of CHM could simultaneously act on the pathological targets of IBS-D, anxiety, and depression.The diverse scope of CHM’s therapeutic role includes various aspects and objectives, underscoring its potential for broad utilization.

show abstract

Section: Discussionmentioning

confidence: 99%

Exploration of the mechanism of Traditional Chinese Medicine for anxiety and depression in patients with diarrheal irritable bowel syndrome based on network pharmacology and meta-analysis

Bai,

Wang,

Wang

et al. 2024

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

Section: Anthocyanins On Gut–brain Axismentioning

confidence: 99%

“…The gut–brain axis is a bidirectional communication network connecting to the central nervous system (CNS), plays a key role in the pathology of AD [ 29 , 30 ]. Emerging evidence suggests that changes in the composition and function of the gut microbiota may influence neuroinflammation, Aβ deposition, and tau pathology, leading to the progression of AD [ 30 , 31 , 32 ]. The gut microbiota produces a variety of neurotransmitters and neuroactive compounds that can modulate neurotransmitter signaling in the brain, influencing cognitive function and behavior.…”

Section: Anthocyanins On Gut–brain Axismentioning

confidence: 99%

“…This modulation of the gut microbiota can influence neurotransmitter production and signaling along the gut–brain axis, potentially impacting cognitive function and behavior [ 36 , 38 ]. Additionally, anthocyanins have been shown to inhibit the aggregation of amyloid-beta peptides and tau protein phosphorylation, two hallmark features of AD pathology which are strongly associated with the gut–brain axis [ 30 , 38 ]. Studies have shown that anthocyanins can enhance gut barrier integrity by promoting the expression of tight junction proteins (Occludin, Claudin, ZO-1), which help maintain the integrity of the gut epithelial barrier, thus reducing the translocation of harmful substances from the gut lumen into the bloodstream [ 39 , 40 ] ( Figure 2 ).…”

Section: Anthocyanins On Gut–brain Axismentioning

confidence: 99%

See 1 more Smart Citation

Therapeutic Effects of Plant Anthocyanin against Alzheimer’s Disease and Modulate Gut Health, Short-Chain Fatty Acids

Bayazid,

Lim

2024

Nutrients

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is the most common form of dementia and neurogenerative disease (NDD), and it is also one of the leading causes of death worldwide. The number of AD patients is over 55 million according to 2020 Alzheimer’s Disease International (ADI), and the number is increasing drastically without any effective cure. In this review, we discuss and analyze the potential role of anthocyanins (ACNs) against AD while understanding the molecular mechanisms. ACNs have been reported as having neuroprotective effects by mitigating cognitive impairments, apoptotic markers, neuroinflammation, aberrant amyloidogenesis, and tauopathy. Taken together, ACNs could be an important therapeutic agent for combating or delaying the onset of AD.

show abstract

“…This includes neuroinflammatory and neurodegenerative diseases, as dysbiosis contributes to gut and brain hyperpermeability, commonly termed ‘leaky gut’ and ‘leaky brain,’ by way of reduced tight junction proteins such as occludins ( 5 ). Microbial metabolites produced during dysbiosis are able to induce barrier dysfunction in preclinical models, leading to the passage of abnormal substances across barriers ( 6 ). The barrier function of the gut and the brain are an important part of innate immunity, without which the immune system cannot function properly, resulting in chronic inflammation locally and, perhaps eventually, systemically.…”

Section: Introductionmentioning

confidence: 99%

The microbiota-gut-brain-immune interface in the pathogenesis of neuroinflammatory diseases: a narrative review of the emerging literature

Warren,

Nyavor,

Zarabian

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

ImportanceResearch is beginning to elucidate the sophisticated mechanisms underlying the microbiota-gut-brain-immune interface, moving from primarily animal models to human studies. Findings support the dynamic relationships between the gut microbiota as an ecosystem (microbiome) within an ecosystem (host) and its intersection with the host immune and nervous systems. Adding this to the effects on epigenetic regulation of gene expression further complicates and strengthens the response. At the heart is inflammation, which manifests in a variety of pathologies including neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and Multiple Sclerosis (MS).ObservationsGenerally, the research to date is limited and has focused on bacteria, likely due to the simplicity and cost-effectiveness of 16s rRNA sequencing, despite its lower resolution and inability to determine functional ability/alterations. However, this omits all other microbiota including fungi, viruses, and phages, which are emerging as key members of the human microbiome. Much of the research has been done in pre-clinical models and/or in small human studies in more developed parts of the world. The relationships observed are promising but cannot be considered reliable or generalizable at this time. Specifically, causal relationships cannot be determined currently. More research has been done in Alzheimer’s disease, followed by Parkinson’s disease, and then little in MS. The data for MS is encouraging despite this.Conclusions and relevanceWhile the research is still nascent, the microbiota-gut-brain-immune interface may be a missing link, which has hampered our progress on understanding, let alone preventing, managing, or putting into remission neurodegenerative diseases. Relationships must first be established in humans, as animal models have been shown to poorly translate to complex human physiology and environments, especially when investigating the human gut microbiome and its relationships where animal models are often overly simplistic. Only then can robust research be conducted in humans and using mechanistic model systems.

show abstract

Gastrointestinal and brain barriers: unlocking gates of communication across the microbiota–gut–brain axis

Cited by 24 publications

References 281 publications

Exploration of the mechanism of Traditional Chinese Medicine for anxiety and depression in patients with diarrheal irritable bowel syndrome based on network pharmacology and meta-analysis

Exploration of the mechanism of Traditional Chinese Medicine for anxiety and depression in patients with diarrheal irritable bowel syndrome based on network pharmacology and meta-analysis

Therapeutic Effects of Plant Anthocyanin against Alzheimer’s Disease and Modulate Gut Health, Short-Chain Fatty Acids

The microbiota-gut-brain-immune interface in the pathogenesis of neuroinflammatory diseases: a narrative review of the emerging literature

Contact Info

Product

Resources

About