Gut-skin axis: Emerging insights for gastroenterologists-a narrative review

Table 1 Key microbial metabolites and their effects on the gut-skin axis

Metabolite	Produced by	Effects on gut	Effects on skin
SCFAs (e.g., butyrate)	Firmicutes (e.g., Faecalibacterium)	Enhances gut barrier, anti-inflammatory	Promotes tregs, reduces inflammation
p-Cresol	Clostridium difficile	Increases gut permeability	Decreases keratinocyte differentiation, causes xerosis
Indole derivatives	Tryptophan metabolism	Modulates intestinal immunity via AhR	Influences skin inflammation and barrier repair
Zonulin	Enteric epithelial cells	Increases intestinal permeability ("leaky gut")	May indirectly increase risk of inflammation-related dermatoses
Serotonin	Enterochromaffin cells/gut flora	Gut motility, mood regulation	Implicated in pruritus and neurogenic inflammation
Trimethylamine-N-oxide	Gut bacteria metabolizing choline/carnitine (e.g., Lachnoclostridium)	Increases systemic inflammation and oxidative stress; implicated in metabolic dysfunction	May contribute to skin aging and inflammatory dermatoses (indirectly via systemic effects)

SCFA: Short-chain fatty acid.

Table 2 Shared cytokine pathways in gut and skin disorders

Cytokine	Source	Role in gut disease	Role in skin disease
IL-17	Th17 cells	Promotes mucosal inflammation in Crohn’s disease; may have protective roles in UC	Drives psoriasis, AD
IL-23	Dendritic cells, macrophages	Supports Th17 expansion in IBD	Involved in psoriatic inflammation
TNF-α	Macrophages, monocytes	Central to both Crohn’s and UC pathogenesis	Targeted in psoriasis, hidradenitis suppurativa
IL-4	Th2 cells	Mucosal immunity shift in some IBD variants	Hallmark of atopic dermatitis
IL-6	Multiple immune cells	Acute phase reactant in IBD	Links gut-brain-skin inflammation
IFN-γ	Th1 cells	Epithelial barrier disruption	Found in psoriatic and alopecia lesions
IL-22	Th17 cells, innate lymphoid cells	Promotes epithelial regeneration, but may drive pathology in IBD (e.g., UC)	Promotes keratinocyte proliferation in psoriasis

IL: Interleukin; UC: Ulcerative colitis; IBD: Inflammatory bowel disease; AD: Atopic dermatitis; IFN-γ: Interferon-gamma.

Table 3 Common diseases/syndromes with their gastrointestinal and skin manifestations

Disease/syndrome	Skin manifestations	Associated GI malignancy	GI and other features
Muir Torre syndrome (Variant of Lynch syndrome)	Sebaceous adenoma. Epitheliomas. Multiple keratocanthomas	Colon, gastric, hepatobiliary, pancreas	Cancer involving endometrium, cervix, lung, urological, blood, ovary
Gardner syndrome	Epidermoid cysts. Lipomas. Desmoid tumors	Colorectal, duodenal, hepatoblastoma, stomach	CHRPE, supernumerary teeth, adrenal tumors, osteomas
Peutz Jegher’s syndrome	Hyperpigmentation of tongue. Pigmentation around lips around mouth	Duodenal, colon, pancreas, stomach, small bowel	Cancer involving pancreas, breast, ovary, genitals
Cowden syndrome	Trichilemmomas. Oral papillomatosis. Facial papules. Acral keratoses	Colon	Melanoma, cancer involving endometrium, thyroid, kidney
Bannayan-Riley-Ruvalcaba syndrome	Hyperpigmented macules involving Glans penis or vulva. Acanthosis nigricans. Facial verrucous papules	None	Macrocephaly, hypotonia, autism spectrum disorder, development delay, hamartomas, seizures, scoliosis
Juvenile polyposis syndrome	Digital clubbing. Facial and digital telangiectasias	Colon, SI, stomach	Cancer involving. Pancreas
Cronkhite Canada syndrome	Nail dystrophy. Alopecia. Hyperpigmentation	Gastric, colon	Intestinal mucosal changes leading to malabsorption
Bazex syndrome (Acrokeratosis Paraneoplastica)	Scaly. Psoriasiform plaques on acral areas, and nasal, ear and malar surfaces	Upper GI tract	SCC of pharynx, esophagus, larynx, lung, lymphoma and genito-urinary tumors
Tylosis	Palmoplantar hyperkeratosis	Esophagus (SCC)
Plummer Vinson syndrome	Koilonychia	Esophagus (SCC)	Esophageal web, iron deficiency
Glucagonoma and Necrolytic Migratory erythema	Annular erythematous eruption with blisters. Ngular cheilitis. Glossitis. Stomatitis		Anemia, weight loss, diarrhoea, steatorrhoea, thromboembolic disease, psychiatry disturbance
Carcinoid syndrome	Flushing. Rosacea. Pellagra like changes. Cutaneous metastasis	Appendix, small intestine	Wheezing, carcinoid heart disease, diarrhoea
Paraneoplastic dermatomyositis	Heliotropic rash. Gottron papules. Violaceous poikiloderma. Ragged cuticle. Nail fold telangiectasias	Stoamch, colorectal, pancreas	Dermatomyositis, cancer involving lung and ovary, lymphomas
Cutaneous metastasis	Sister Joseph Mary nodule on umbilicus	Gastric adenocarcinoma

GI: Gastrointestinal; SCC: Squamous cell carcinoma; SI: Small intestine; CHRPE: Congenital hypertrophy of the retinal pigment epithelium.

Table 4 Gut-skin axis–linked diseases and their microbial dysbiosis profiles

Condition	Gut microbiome changes	Skin microbiome changes
Atopic dermatitis	↓Bifidobacteria, ↓F. prausnitzii, ↑Enterobacteriaceae	↑S. aureus, ↓microbial diversity
Psoriasis	↑Ruminococcus, ↓Akkermansia muciniphila, ↓Faecalibacterium prausnitzii	↑Corynebacterium, ↑Streptococcus
Rosacea	↑Prevotella intermedia, ↓Cutibacterium	↑Demodex folliculorum, ↑Gordonia
Hidradenitis suppurativa	↑Porphyromonas, ↑Prevotella, ↓diversity	↑anaerobes in lesions, ↓alpha diversity
Celiac disease	↑Proteobacteria, ↓Lactobacillus, ↑Candida	Associated with dermatitis herpetiformis
Seborrheic dermatitis	Altered lipid metabolism-related bacteria (e.g., ↑Enterobacteriaceae)	↑Malassezia species (esp. M. restricta), altered yeast load
Acne vulgaris	↓Lactobacillus, ↑Proteobacteria, ↓diversity	↑Cutibacterium acnes (formerly Propionibacterium acnes)