Enteric nervous system as a therapeutic target in gastrointestinal disorders

Table 1 Studies showing therapeutic role of enteric nervous system on functional bowel disorders

No.	Ref.	Study characteristics	Key role of ENS
1	Baj et al[54]	Investigates the potential therapeutic use of marine toxins in treating visceral pain associated with gastrointestinal disorders	Focuses on the role of ENS in visceral pain perception and potential modulation via marine toxins
2	Bosi et al[55]	Examines how hyaluronan regulates neuronal and immune function in the rat small intestine and microbiota following ischemia/reperfusion injury	Highlights the ENS's involvement in gut motility and immune responses, particularly in the context of injury
3	Chai et al[56]	Studies the role of stem cell growth factor/c-Kit in the pathogenesis of IBS	Focuses on ENS's involvement in the pathophysiology of IBS, particularly in neuroimmune interactions
4	Chang et al[57]	Investigates how targeting enteric glial CRF-R1/Cx43 attenuates stress-induced accelerated colonic motility	Demonstrates the role of enteric glia and receptors in stress-induced gastrointestinal dysfunction
5	Chen et al[58]	Explores how patchouli alcohol restores gut homeostasis in IBS with diarrhea through neurotransmitter regulation via myosin Va	ENS plays a key role in restoring intestinal balance and regulating gut motility in IBS through neurotransmission
6	Cheng[59]	Identifies calcium-sensing receptor as a new therapeutic target for diarrhea	Focuses on how ENS receptors can be targeted to improve gastrointestinal disorders, specifically diarrhea
7	Del Colle et al[60]	Explores novel aspects of enteric serotonergic signaling in both health and brain-gut diseases	Examines serotonergic signaling in the ENS and its implications for gut function and diseases like IBS
8	Dong et al[61]	Investigates the role of Na+/Ca2+ exchanger 1 as a mechanosensitive molecule in esophageal myenteric neurons	Highlights the mechanosensitive role of ENS neurons in regulating esophageal motility and responsiveness
9	Guarino et al[62]	Explores the role of the gastrointestinal neuromuscular apparatus as an underestimated target of gut microbiota	Focuses on the interaction between ENS, microbiota, and neuromuscular function in gastrointestinal health
10	Gulbransen and Christofi[63]	Investigates the potential of targeting enteric glia in gastrointestinal diseases and motility disorders	Highlights the emerging therapeutic role of enteric glia in modulating motility disorders and disease states
11	Holland et al[64]	Discusses the regulation of microRNA in enteric nervous system development and its role in disease	Emphasizes the role of microRNAs in ENS development, function, and the onset of gastrointestinal diseases
12	Holzer and Holzer-Petsche[65]	Studies how anti-calcitonin gene-related peptide migraine therapeutics may cause constipation by antagonizing the motor functions of the intestine	Examines the ENS's involvement in gastrointestinal motility affected by treatments for other conditions
13	Kimono[66]	Discusses gastrointestinal issues and therapeutic approaches in Gulf War illness	Focuses on the complex interplay between the ENS and the broader neurological and immune systems in disease contexts
14	Linan-Rico et al[67]	Investigates the role of enteric glial cells in inflammation and their potential therapeutic implications for GI diseases	Highlights the critical role of ENS glial cells in inflammation and their therapeutic potential in gastrointestinal disorders
15	Mace et al[68]	Provides insights into the pharmacology and physiology of gastrointestinal enteroendocrine cells	Explores the interaction between ENS and enteroendocrine cells in regulating gut physiology and responses
16	Morales-Soto and Gulbransen[69]	Discusses how enteric glia significantly contributes to abdominal pain in gastrointestinal discomfort	Sheds light on the role of ENS glial cells in mediating abdominal pain and their emerging role in therapeutic strategies
17	O'Mahony et al[70]	Examines the connection between early-life stress and the development of irritable bowel syndrome and psychiatric comorbidities	Investigates the role of the ENS in the brain-gut axis, highlighting its importance in IBS and related conditions
18	Tait and Sayuk[71]	Studies the brain-gut-microbiota axis in functional gastrointestinal illnesses and potential therapeutic interventions	Explores the role of the ENS as a mediator between the brain, gut, and microbiota in functional gastrointestinal disorders
19	Weber[72]	Discusses new treatment options for irritable bowel syndrome with predominant diarrhea	Focuses on therapeutic targets within the ENS to treat IBS with diarrhea
20	Zhang et al[73]	Explores how EphrinB2/ephB2 activation facilitates colonic synaptic potentiation and contributes to long-term visceral hypersensitivity in IBS	Focuses on the role of synaptic plasticity in the ENS, contributing to visceral hypersensitivity in IBS

ENS: Enteric nervous system; IBS: Irritable bowel syndrome; GI: Gastrointestinal; RNA: Ribonucleic acid.

Table 2 Studies showing therapeutic role of enteric nervous system on inflammatory bowel disease

No.	Ref.	Study characteristics	Key role of ENS
1	Belarif et al[91]	Investigates the influence of the IL-7 receptor on anti-TNF responsiveness and T-cell gut homing in IBD	Focuses on how the IL-7 receptor affects the ENS by influencing T-cell migration and responsiveness to anti-TNF therapy
2	Boldyreva et al[92]	Highlights the gut-brain axis and non-obvious factors involved in IBD	Explores the communication between the ENS and brain, and how it impacts the development and progression of IBD
3	Bosáková et al[93]	Studies the role of serotonin in attenuating TNF-induced intestinal inflammation through interaction with human mucosal tissue	Investigates serotonin's effects on the ENS and its potential to modulate inflammation in the gut via interaction with mucosal tissue
4	Hawker et al[94]	Explores the role of Mas-related G protein-coupled receptors in gastrointestinal dysfunction and IBD	Examines the involvement of Mas-related receptors in ENS-mediated gastrointestinal functions, particularly in IBD
5	Lê et al[95]	Reviews therapeutic strategies for IBD involving modulation of the microbiota and the introduction of pre-, pro-, syn-, or postbiotics	Focuses on how microbiota manipulation impacts ENS function, providing new therapeutic strategies for IBD management
6	Ochoa-Cortes et al[96]	Discusses enteric glial cells as a new frontier in neurogastroenterology and a potential clinical target for IBD	Highlights the growing importance of enteric glial cells in IBD, providing potential new targets for clinical treatment
7	Robinson et al[97]	Investigates the neuroprotective effects of bone marrow mesenchymal stem cells in TNBS-induced colitis	Demonstrates how stem cells interact with the ENS to protect against damage and restore function in gastrointestinal disorders
8	Sahakian et al[98]	Identifies molecular targets to alleviate enteric neuropathy and gastrointestinal dysfunction	Focuses on targeting specific molecules in the ENS to relieve neuropathy and restore normal gastrointestinal function
9	Stavely et al[99]	Explores strategies for targeting enteric neurons and plexitis as a way to manage IBD	Emphasizes the role of enteric neurons and the plexuses in managing inflammation and dysfunction in IBD

ENS: Enteric nervous system; IBD: Inflamatory bowel disease; TNF: Tumor necrosis factor; TNBS: Trinitrobenzenesulfonic acid.

Table 3 Studies showing therapeutic role of enteric nervous system on gastrointestinal motility disorders

No.	Ref.	Study characteristics	Key role of ENS
1	Bessard et al[112]	Investigates alterations in prostanoid expression and intestinal epithelial barrier functions that contribute to ileus	Highlights how disruptions in ENS signaling and epithelial function lead to impaired motility and ileus development
2	Bonaz[113]	Discusses the role of enteric neuropathy and the vagus nerve in gastrointestinal disorders, with therapeutic implications	Explores how enteric neuropathy and vagal signaling impact gut function, offering insights into treatment strategies
3	Brun et al[114]	Studies how Toll-like receptor-2 regulates glial-derived neurotrophic factor production in intestinal smooth muscle cells	Focuses on how glial cells in the ENS influence smooth muscle function and gut motility via neurotrophic factor production
4	Ferreira-Duarte et al[115]	Explores the interaction between the renin-angiotensin system and enteric neurotransmission in colonic dysmotility in TNBS-induced colitis	Highlights the interplay between systemic signaling and the ENS, leading to dysmotility in inflammatory conditions like colitis
5	Filpa et al[116]	Investigates the role of glutamatergic neurotransmission in the ENS and its role in the brain-gut axis in health and disease	Explores how glutamate signaling in the ENS influences gut-brain communication and impacts gastrointestinal disorders
6	Floettmann et al[117]	Provides the pharmacological profile of Naloxegol, a peripherally acting μ-opioid receptor antagonist for opioid-induced constipation	Focuses on the interaction between opioid receptors in the ENS and peripheral opioid antagonism to treat constipation
7	Gao et al[118]	Investigates μ-opioid receptor-mediated enteric glial activation in morphine-induced constipation	Highlights the activation of enteric glia through opioid receptors, contributing to constipation in opioid use
8	Sanger et al[119]	Discusses the role of ghrelin and motilin control systems in gastrointestinal physiology and therapeutics	Explores the control of gastrointestinal motility via ghrelin and motilin systems, which interact with the ENS for motility regulation
9	Stakenborg et al[120]	Reviews pathophysiology and current therapeutic approaches to postoperative ileus	Discusses how the ENS is involved in the pathophysiology of ileus and how therapies targeting ENS dysfunction can improve recovery

ENS: Enteric nervous system; TNBS: Trinitrobenzenesulfonic acid.