Gut-brain axis and post-operative cognitive dysfunction: A multifactorial perspective on microbiota, inflammation, and cognitive health

Table 1 Summary of gut microbiota alterations, mechanistic pathways, cognitive impacts, and interventions across various cognitive disorders

Cognitive disorder	Key gut microbiota changes	Mechanistic pathways	Impact on cognition	Microbiota-targeted interventions	Ref.
Post-operative cognitive dysfunction	↓ A. muciniphila, ↓ Lactobacillus, ↓ Bifidobacterium; dysbiosis post-surgery, anesthesia, antibiotics	↑ Gut permeability → systemic LPS → neuroinflammation; ↓ SCFAs → BBB compromise; microglial activation & synaptic loss	Memory & attention deficits post-surgery; delayed recovery	VSL#3, Peifeikang probiotics; SCFA supplementation; gut barrier restoration	[7,9,12,16,20]
Hepatic encephalopathy	Dysbiosis: ↑ pathogenic taxa, ↓ SCFA producers	↑ Ammonia & endotoxemia → systemic & neuroinflammation; impaired hepatic detoxification	Confusion, poor executive function	Probiotics, prebiotics, FMT	[18,21,22,45]
Obesity & type 2 diabetes	↓ A. muciniphila, ↑ Gram-negative bacteria	Endotoxemia (LPS) → insulin resistance; hippocampal dysfunction	Cognitive decline, poor executive function	A. muciniphila supplementation; dietary modulation	[1,18,23,24]
Non-alcoholic fatty liver disease	Altered bile acid metabolism; ↓ A. muciniphila	Ammonia & bile acid dysregulation; chronic inflammation	Memory & attention deficits	Probiotics; bile acid-targeted therapies	[21,22,25]
Alzheimer’s disease	↓ SCFA-producing bacteria; ↓ A. muciniphila	Microglia activation; ↑ TNF-α, IL-6	Memory loss; cognitive decline	A. muciniphila, multi-strain probiotics, FMT	[26-28]
Parkinson’s disease	Dysbiosis; ↓ SCFA producers; ↓ A. muciniphila	Gut inflammation → α-synuclein aggregation; gut–brain immune signaling	Motor & cognitive symptoms	Probiotics, diet, FMT	[29-31]
Depression	↓ Microbial diversity; altered Firmicutes/Bacteroidetes ratio	SCFAs regulate serotonin & dopamine; hypothalamic-pituitary-adrenal axis activation	Low mood; impaired cognition	Psychobiotics, probiotics, fiber	[32-34]
Schizophrenia	↓ A. muciniphila; dysbiosis	Barrier dysfunction; systemic inflammation; neurotransmitter disruption	Cognitive impairment; psychosis	Early microbiota therapy research	[35]
Multiple sclerosis	Dysbiosis; ↓ SCFA producers	Immune dysregulation → demyelination; ↑ cytokines	Poor memory; cognitive decline	Next-gen probiotics; A. muciniphila	[36,37]
Rheumatoid arthritis	Altered gut microbiome; ↓ A. muciniphila	Chronic inflammation; compromised BBB	Brain fog; fatigue	Probiotic therapies (research)	[38,39]
Chemo brain (cancer therapy cognitive impairment)	Severe microbiota disruption post-chemo	LPS & cytokines → neuroinflammation; SCFA depletion	Memory loss; slower processing	A. muciniphila, probiotics, FMT	[40,41]

POCD: Post-operative cognitive dysfunction; A. muciniphila: Akkermansia muciniphila; LPS: Lipopolysaccharides; SCFAs: Short-chain fatty acids; FMT: Fecal microbiota transplantation; TNF-α: Tumour necrosis factor alpha; IL-6: Interleukin-6; BBB: Blood-brain barrier.