Colon: Digestion, absorption and fermentation

Pathway of food waste from point of entry into large intestine through its exit from the body as faeces

Interactions between mucus layer, gut microbes and health

Function of mucus layer in intestinal tract

Discuss factors that determine colonic fermentation

Absorption of electrolytes, water and vitamins:


  1. Ion channels, carriers and pumps, located either on the luminal or basolateral membrane, allowing highly efficient transport of large amounts of salt and water


  2. Colonic absorption of ~1.5L of electrolyte-rich fluid per day


  3. Net transport is the result of well-balanced absorption and secretion


  4. Ion transported is disturbed during infectious diseases causing secretory diarrhoea (can cause life threatening dehydration by excessive loss of salts and water)

Secretion of compounds in to the lumen:


  1. Secretory epithelial cells contain Cl- and K+ channels in their luminal membranes allowing for secretion of KCL


  2. Bicarbonate (HCO3-) secreted into the lumen determines pH on the surface of the colonic mucosa as it is alkaline. It possibly works as a buffer.


  3. Mucus produced by goblet cells are also secreted into the lumen

Defecation:


  1. When faeces fills the sigmoid colon, faeces flow over in the rectum and creates distention


  2. Stretch receptors send signals to the spinal cord


  3. Signals are subsequently sent to the internal anal sphincter for it to relax (it is felt as urge to defecate)


  4. The presence of faeces in the anal canal sends a signal to the brain, which gives you the choice of voluntarily opening the external anal sphincter (defecating) or keeping it temporarily closed

Colonic Digestion:


The Enteric Nervous System (largest component of autonomic nervous system)


  1. It is equipped with intrinsic microcircuits that enable it to orchestrate GI function independently of CNS input


  2. Neural and endocrine control of digestion is closely coordinated


  3. Colonic motility is dependent on the ENA for propulsion of contents

Sensing of mechanical forces:


  1. Distension in the gut - ingested and secreted material
  • gas produced by microbial fermentation

  1. Mechanosensory cells - mechanical force gets traduced by several proteins in the mechanoreceptor


    -Responses are amplified and signalling molecules are released


  2. Mechanosensory circuits built into the GI wall allow for spatial and temporal integration of mechanical stimuli into a coordinated physiological response

GI Motility in the large intestine:


Haustral contractions:

  1. Type of segmentation
  2. Triggered by stretch
  3. Occurs primarily in ascending and transverse colon
  4. Increase mixing, contact to mucosal surface, increase absorption

Peristalsis

  1. Coordinated, involuntary propulsion of food

Mass movements (peristalsis)

  1. Occur 3-5 times per day (during or after meals)
  2. Triggered bys stretch, luminal irritants and gastrocolic reflex
  3. Propulsion to rectum
  4. Occur primarily in transverse and descending colon

Diet:


High-fibre diet up-regulates colonic fermentation and relative abundance of beneficial bacteria in the colonic microbiota. This is due to the higher production of SCFAs, which fuel the gut bacteria, gut integrity and has anti-inflammatory effects.

What is the gut mucus layer?


  1. Mucus is composed of water, electrolytes, lipids, proteins and others


  2. it covers the intestinal epithelial surface


  3. The key structural component of mucus protein is mucin which gives the mucus a dilute, aqueous and viscoelastic structure


  4. The mucus is vital for maintaining Intestinal health

Structure and synthesis of mucin:


  1. The mucin domain contains a protein core composed of sequences contains the amino acid residues proline, throning, and serine
  2. pralin ensures that the structure reminds unfolded in the Golgi apparatus, allowing O-glycosylation

Glycosylation (addition of sugar moieties to specific amino acids)


  1. Glycans differs along the different regions of the digestive tract and among individuals

(a) Due to different: expression of glycosyltransferases, state of health, microbial colonisation


  1. Glycans of the mucus in the distal colon are however rather uniform


  2. Classification of mucus



(a) transmembrane mucins: synthesised and attached to the cell membrane of the enterocytes and the primary function is cell protection


(b) gel-forming mucins: secrete and synthesised by the goblet cells

Small Intestine Mucus:


Mucuis is synthesised in the goblet cells in the crypts


The goblet cell-to-entrocyte ratio changes along the intestinal tract (proportional to no. of microorganisms)


The mucus layer is relatively porous and penetrable to different components as well as bacteria

Large Intestine Mucus:


  1. Mucus is organised in an inner and outer layer


  2. the inner mucus layer is continuously refilled by the MUC2 murine (constant thickness), is anchored to the goblet cells, and remains attached to the epithelium


  3. The outer mucus layer begins at a certain distance from the epithelium, where the inner mucus is converted by endogenous proteases into the outer mucus layer, forming a sharp border that separates the two

Mucus turnover and degradation:


  1. Mucus synthesis, secretion and degradation is a delicate process


  2. In the small intestine, the turnover of Muc2 mucin is lower in the goblet cells of the crypts than along the villi


  3. In the colon, the surface goblet cells continuously secrete the inner mucus layer, while the goblet cells in the upper part of the colonic crypts secrete mucus in response to stress stimuli


  4. Mucus degradation generally occurs due to physical disruption by mechanical shear forces of peristalsis and enzymatic cleavage by microbial enzymes

The role of mucus:


Primary role of mucus is to protect the intestinal epithelium against:


(a) mechanical force (peristalsis)
(b) chemical attacks (toxic compounds)
(c) biological attacks (digestive enzymes, bacteria)

Diffusion barrier: Ions, water, nutrients and gases an readily diffuse through and reach the enterocytes (absorption)

Mucus operates as a surface cleaner removing debris and bacteria through binding, collecting and flushing via the intestinal flow

First line of immunological defence: .


Reduces exposure to antigens and bacteria = possible harmful products


MUC are able to bind directly to immune cells and affect their activity

Mucus-associated microbiota:


The intestinal mucus layer represents a selective habitat:


(a) bacteria can attach to the mucus
(b) bacteria can utilise mucus and stimulate mucus production
(c) mainly the outer mucus layer is colonised


HOWEVER, some bacteria are able to penetrate the mucus and colonise the inner layer. Some mucin-degrading bacteria appear to be beneficial, whereas other as detrimental.

Regulation of mucus depends on:


Host factors - host metabolic, epigenetic, ut motility


External factors - commensal and pathogenic bacteria, probiotics, diet, food additives or contaminants, antibiotics

Transit time:


A higher transit time results in a higher pH in the colon and a higher microbial diversity.

Substrate Availability:
Starch, non-stach polysaacharides, proteins and nitrogen, mucins