Gastrointestinal tract

The gastrointestinal tract comprises the stomach and intestines, where food is digested, nutrients are absorbed and remaining material is processed before elimination. Although these functions are conserved across mammals, the anatomy and organization of the gastrointestinal tract vary between species, reflecting differences in diet, digestive physiology and microbial fermentation.

The sampled tissues include stomach, duodenum, jejunum, ileum, cecum, colon and rectum. In macaque, rat and mouse, the stomach was sampled from upper, middle and lower regions, whereas only the middle region was sampled in pig. These regions are combined into a single main tissue type, stomach, for the tissue specificity analysis.

For the intestines, the mammalian RNA data distinguish between small intestine (duodenum, jejunum and ileum) and large intestine (cecum, colon and rectum), whereas the human consensus RNA data represent the intestine as a single group. To enable consistent cross-species comparisons, the broader intestine category is therefore recommended for tissue specificity analysis. The cecum is included in the mammalian datasets but is not included in the human RNA data. Differences in intestinal anatomy and the anatomical coverage of samples should be considered when interpreting cross-species expression patterns.

Figure 1. Tissue sample overview and the hierarchy of grouped tissues representing gastrointestinal tract

Comparative transcriptomics of the mammalian gastrointestinal tract

The transcriptomic data is used to identify genes with elevated expression in individual tissues or groups of tissues, classified into three categories:

Tissue enriched: Genes with elevated expression in a single tissue compared with all other tissues.
Group enriched: Genes with elevated expression in a limited group of tissues compared with the remaining tissues.
Tissue enhanced: Genes with elevated expression in one or more tissues compared with the average expression across tissues (gap ratio ≥2)

Tissue specificity is evaluated at two levels: first, within each species using all available tissue types, and second, using only tissues that can be directly compared between the species and human. This distinction makes it possible to explore both tissue-specific expression within each species and the conservation of expression patterns across evolution.

The results can be explored for individual genes on the gene summary pages or searched to identify genes with specific expression patterns. To assess evolutionary conservation, pairwise overlap analysis compares each species individually with human, identifying genes that share the same tissue specificity classification in corresponding tissues and quantifying the extent of overlap between species.

Tissue	Species	Elevated	Human elevated overlap
Tissue	Species	Elevated	Complete overlap	Partial overlap
Large intestine	Macaque	176	n/a	n/a
	Mouse	293	n/a	n/a
	Rat	334	n/a	n/a
	Pig	208	n/a	n/a
Small intestine	Macaque	400	n/a	n/a
	Mouse	484	n/a	n/a
	Rat	353	n/a	n/a
	Pig	249	n/a	n/a
Stomach	Macaque	238	33	57
	Mouse	292	28	46
	Rat	268	34	36
	Pig	282	24	44

Stomach

The stomach shows particularly pronounced anatomical and histological differences between mammals. Humans and macaques have predominantly glandular stomachs, whereas rats and mice have a substantial nonglandular forestomach lined by keratinized squamous epithelium, separated from the glandular stomach by a limiting ridge. Pigs also have a nonglandular esophageal region, although its organization differs from that of rodents. Consequently, stomach samples collected from different anatomical regions may show substantial differences in epithelial and digestive enzyme-related gene expression. In macaque, rat and mouse, the stomach was sampled from upper, middle and lower regions, whereas only the middle region was sampled in pig. These regions are combined into a single main tissue type, stomach, for the tissue specificity analysis.

Species coverage

Small intestine

Duodenum

The duodenum receives digestive enzymes and bile and contains specialized epithelial cells involved in nutrient absorption and intestinal protection. Brunner's glands, which produce alkaline mucus, differ in their anatomical distribution and extent across species, potentially contributing to differences in secretory gene expression.

Jejunum

The jejunum is a major site of nutrient absorption and contains intestinal villi, crypts and specialized epithelial cell populations. Although this organization is conserved, villus morphology, intestinal length and the distribution of immune tissues vary across species, with pigs having well-developed jejunal Peyer's patches.

Ileum

The ileum contributes to nutrient absorption, bile acid recycling and immune surveillance. Its lymphoid organization differs between mammals, with pigs having a particularly extensive continuous ileal Peyer's patch, whereas humans and rodents have a different arrangement of intestinal lymphoid follicles.

Species coverage

Human small intestine includes both jejunum and ileum

Large intestine

Cecum

The cecum is particularly variable in size and function across mammals, reflecting differences in digestive physiology. It is highly developed in rats and mice, where it serves as a major site of microbial fermentation, whereas humans and macaques have a relatively smaller cecum and pigs have an intermediate hindgut fermentation system. These differences may influence the composition of epithelial, immune and microbial-associated gene expression profiles.

Colon

The colon absorbs water and electrolytes and supports extensive interactions with the intestinal microbiota. Its length, organization and fermentation capacity differ across mammals, with rodents having a relatively simple colonic arrangement and pigs possessing a distinctive spiral colon associated with their hindgut digestive physiology.

Rectum

The rectum stores faecal material before defecation and contains specialized muscular and epithelial structures involved in continence. Its basic organization is conserved across mammals, although differences in intestinal anatomy, epithelial composition and the transition to the anal canal may influence gene expression.