Intra-uterine development of the gut
The gut is the first organ to develop in the second week after fertilisation when the embryo is a disc of cells. The thyroid and parathyroid glands, thymus, respiratory tract, liver, pancreas, bladder and kidneys all develop from the primitive gut.

It is well known that the foetus receives nutrition intravenously from the placenta but the gut makes an important contribution. Swallowing begins at 11 weeks and the amniotic fluid which the baby ingests helps them grow, as shown by the fact that babies unable to swallow before birth are lighter. Swallowing is sometimes accompanied by co-ordinated emptying of the stomach¹.

Post-natal development of the gut
After birth, the gut must supply the total nutritional needs of the newborn baby within a day or two after birth. This demand presents a particular challenge to the premature baby, whose gut is hardly able to contract and, if born before 35 weeks, will be unable to suck. The gut is sterile at birth and must cope with the influx of billions of bacteria. Small wonder this process can go wrong, especially if the premature infant has been poorly nourished before birth. One of the most feared complications of premature delivery, necrotising enterocolitis (NEC), is a form of gas gangrene of the gut, in which the intestinal bacteria invade the damaged intestine². Feeding premature babies at risk for NEC with expressed breastmilk decreases the risk. Established NEC is treated by intravenous feeding, broad spectrum antibiotics and surgical removal of the damaged intestine. If an excessive length of intestine is removed, the baby is left with the short bowel syndrome, requiring long-term intravenous feeding and careful introduction of enteral nutrition with expressed breastmilk and an amino acid formula such as Neocate³.

Gut problems in the first year of life
Babies have been described as ‘gastro-intestinal tracts with no responsibility at either end’ parents of a newborn baby will readily identify with this description. Taking a lead from this definition, we will track along the infant’s gut, noting problems which can occur along the way.

Mouth and pharynx
Healthy, full term infants have a very effective sucking and swallowing mechanism within a few days of birth. This is just as well as, in order to swallow their daily requirement of milk they are called on to drink 150ml/kg which would be the equivalent of 10 litres in an adult. Premature babies and those with neurological impairment do not have it so easy hence the use of nasogastric feeding in these infants. The mechanism by which solid foods are transferred from the front of the tongue to the pharynx does not normally appear until about seven months. There may be a critical period to develop this ability. As with co-ordination of any complex movement, babies improve with time but some take longer than others, showing incoordination of the pharyngeal muscle. They choke and retch on their feeds especially when solid foods are introduced. Paediatric speech therapists have much to offer, by introducing a series of dissolve and swallow foods over time.

Oesophagus and Stomach
Another muscle vital to successful gut function is the lower oesophageal sphincter’. The sphincter is supposed to open to let swallowed food into the stomach, and then shut to prevent it from returning to the oesophagus and mouth. While doing this, the sphincter is meant to allow swallowed air to be ‘burped’. What is more surprising is the fact that the sphincter is not an anatomical structure but works by a combination of the oesophagus being gripped by the diaphragm as it passes through and the fact that the pressure on the oesophagus in the abdomen is higher than the pressure in the thorax. Small wonder that, in babies with poorly co-ordinated movements, the action of the lower oesophageal sphincter is less efficient. This is the basis of gastro-oesophageal reflux which occurs as the sphincter relaxes when it should be contracted. William Shakespeare was obviously familiar with the frequency of GOR in babies, when he wrote about ‘the infant mewling and puking in the nurse’s arms’. GOR is universal in all age groups, but more frequent and obvious in babies who spit out refluxed food rather than swallow it back down. This ability is learned towards the end of the first year of life. At the same time babies at this age spend more time vertical and eat more solids which make reflux less likely. These factors, together with more co-ordinated activity of the sphincter, mean that GOR improves in over 95 per cent of infants at this time. Breastfed babies generally have less of a problem with reflux because breastmilk leaves the stomach faster than formula leaving less opportunity for reflux to occur. Treatment is not required in a thriving baby, who is regurgitating rather than vomiting and is not upset by the GOR. This is easier to say but more difficult in practice for a mother whose house is being transformed into a ‘cheese factory’ by their baby’s incessant regurgitation. The problem may have become commoner in recent years since the introduction of the ‘back to sleep’ campaign because reflux occurs most often when the baby is lying on their backs and is less frequent when lying face down. Transporting babies in car seats has the same effect. Infant Gaviscon may help or using a thickened formula such as Cow & Gate Comfort or Aptamil Easy Digest⁵.

Babies who are crying excessively, arching their backs, pulling away during feeds, vomiting and choking have progressed from GOR to GORD (gastro-oesophageal reflux disease). Premature babies may also show apnoea due to stimulation of the vagus nerve by the presence of gastric contents in the oesophagus. The reflux of gastric acid into the oesophagus causes heartburn and inflammation of the oesophagus (oesophagitis). Babies with GORD require small, frequent feeds, antacids (omeprazole or lansoprazole) and the anti-vomiting drug domperidone⁶. Failure to respond raises the question of whether the symptoms are being aggravated by cows’ milk protein allergy. The oesophagus becomes inflamed with eosinophils (eosinophilic oesophagitis). This problem is becoming more frequent as children in general are developing more allergies. Although breastfeeding is the best strategy for preventing allergies, breastfed babies are not immune to this problem as they can be sensitised to the traces of cows’ milk protein in breastmilk derived from dairy products in the mothers’ diet. Eosinophilic oesophagitis is more likely in an allergic baby with eczema and a family history of atopy but is difficult to differentiate clinically from GORD. Since both GORD and milk allergy are common they can occur together. A trial of maternal dairy free diet for breastfed babies is required, ensuring that the mother`s calcium stores are not compromised through dietary advice or offering supplements. In bottle-fed babies, if babies with GORD are not improved by a formula where the protein is substituted by amino acids such as Neocate, then cows’ milk protein is not involved in their symptoms and, if they fail to respond to medical treatment, assessment by a paediatric gastroenterologist may be the next step.

Small intestine
The small intestine has the vital function of turning what you eat into you. It is assisted by bile salts from the liver which are detergents which dissolve fat, thereby assisting fat absorption. Once again premature infants are disadvantaged here by having decreased production of bile salts. Enzymes are normally provided by the pancreas to digest protein (trypsin and chymotrypsin) fat (lipase) and starch (amylase). The diet of a newborn baby does not contain starch until weaning and, interestingly the digestive juice from the neonatal pancreas contains no amylase. Other digestive enzymes for lactose (lactase) and sucrose (sucrase) are found in the lining of the small intestine.

Human breastmilk and infant formulae contain large amounts of lactose (7g/100ml compared to 4g/100ml in cows’ milk). Lactose cannot be absorbed until it is split into glucose and galactose by lactase. Surprisingly this vital enzyme is more vulnerable to any factors which damage the small intestine. Sucrase, which is an enzyme not required in early life until introduction at weaning, is, by comparison with lactase, much more robust.

Transient lactose intolerance occurs during acute diarrhoea and vomiting. The most common cause in infancy is rotavirus, which damages the small intestine. Once again the functional reserves of the small intestine come to the rescue, allowing breastfeeding to continue. Breastfed babies have less severe diarrhoea than those who are fasted during diarrhoea. Modern infant formulae are also well tolerated during acute diarrhoea and vomiting and do not require diluting. Absorption of glucose from oral rehydration salts is also preserved allowing successful oral rehydration therapy.

Rarely, diarrhoea becomes prolonged after an episode of acute diarrhoea. If the baby’s weight gain is affected, then lactose intolerance secondary to the infection may be responsible and a trial of a low lactose or lactose free milk is recommended. Breastfed babies should continue to feed as breastmilk will help recovery⁷.

Another cause of lactose intolerance in infants results from damage to the small intestine by cows’ milk allergy which results if chronic diarrhoea and growth faltering. My practice is to carry out a trial of Neocate to resolve this problem.

Another important fact about lactase is that the majority of the human population and all other mammals are lactose intolerant in later life. Showing good intestinal housekeeping, lactase production is switched off in mammals after weaning when ingestion of milk is no longer expected. In humans, the ability to digest lactose in adult life is preserved only in populations with a history of dairying going back several thousands of years, largely in societies of northern European origin. This ability is due to a dominantly inherited mutation which improved survival by allowing consumption of milk in large quantities by adults without producing diarrhoea and abdominal pain. Of note is that people who live around the Mediterranean prefer hard cheese to cottage cheese and drink yoghurt rather than fresh cows’ milk thereby limiting their lactose intake.

Large intestine
Infantile colic is another cause of excessive crying. Affected babies scream for hours on end, especially in the evening. The fact that the screaming and drawing up of the legs can start with feeds and may be temporarily relieved by passage of flatus suggests that abdominal pain is the cause. Lactose intolerance has been implicated in colic, the theory being that unabsorbed lactose stimulates the production of gas by bacteria in the large intestine and the resulting intestinal distension causes the pain. A preparation of lactase extracted from yeast (Colief) has been investigated as a treatment for colic. Drops of the extract are added to bottles of prepared formula which are then stored in the refrigerator for half an hour while the lactase in Colief breaks down the lactose in the formula. This approach is not feasible in breastfed babies who are just as likely to have colic as artificially fed babies. One difficulty with this theory is that lactose intolerance should be associated with diarrhoea as the lactose, undigested in the small intestine, draws out fluid from the large intestine by osmosis.

A hypothesis for the cause of colic is that it is a symptom of cows’ milk protein allergy because some babies improve with a milk free diet. A formula containing hydrolysed milk protein, such as Cow & Gate Pepti-Junior or an elemental formula such as Neocate are required as soy-based formulae are ineffective⁸. As noted above cows’ milk allergy may be complicated by lactose intolerance and this may explain the effectiveness of Colief in some babies. Another hypothesis is based on the possibility that a disturbed intestinal flora predisposes to colic. This may occur as a result of babies, especially preterm infants, being born in hospital into a relatively germ-free environment and receiving antibiotics. This in turn could predispose to the development of cows, milk allergy. With this in mind, Infacol Probiotic Colic Drops, containing bifidobacteria, have been developed with the hope of correcting the intestinal flora with ‘friendly’ bacteria⁹. Of possible relevance to their effectiveness is that ‘friendly bacteria’ decrease intestinal inflammation, do not produce gas in the bowel and both prevent and treat allergy.

Cows’ milk protein allergy can manifest itself in the large intestine by producing an allergic colitis¹⁰. Streaks of blood mixed with mucus appear in the stools. As with GERD, breastfed babies may develop allergic colitis triggered by trace amounts of cows’ milk in breastmilk. The treatment is by withdrawing dairy products, and often soy protein from the diet of breastfeeding mothers and changes bottle-fed babies to Neocate. Those in who bleeding continues on exclusion of dairy products need further investigating. In those who respond, the colitis is usually temporary and dairy products can be reintroduced in a few months.

Most of the microbes in the gut are in the large intestine, where they may number 10¹⁴/g of intestinal content. Apart from their sheer numbers and diversity (400 different species with perhaps four times that many still to be isolated) they attracted little attention so long as they stayed where they were. In the last decade there has been an explosion of interest. Having an intestinal flora composed of bifidobacteria and lactobacilli may protect against the development of allergy and eczema and boost the immune system to prevent infection. Later in life, these bacteria may prevent bowel cancer by suppressing those micro-organisms which produce toxic compounds such as nitrosamine. After exposing the large intestine these carcinogenic substances they are absorbed and pass to the bladder, where they cause bladder cancer.

The large intestine of a healthy breastfed baby is full of bifidobacteria and lactobacilli and their presence may explain many of the health benefits of breastfeeding¹¹. The vital ingredients in breastmilk which encourages the growth of these friendly bacteria are complex sugars, called oligosaccharides, present at a concentration of 1g/100ml which makes them the fourth highest constituent after lactose protein and fat. Oligosaccharides (also known as prebiotics) composed of fructose and galactose have been added to Cow & Gate and Aptamil infant formulas to convey similar protection to formula fed babies. An additional ‘spin off’ from ingesting oligosaccharides is that the stools acquire the physical characteristic and composition of the stools of breastfed babies, thereby preventing and alleviating constipation.

Conclusion
This overview of the ills which can affect the infant gastro-intestinal tract reaffirms the importance of breastfeeding to the welfare of babies. Bottle-fed babies can now share some of these advantages providing they consume a formula containing fructose and galactose oligosaccharides such as Cow & Gate. If a mother can’t or chooses not to breastfeed, practitioners can now recommend specific formulas containing oligosaccarides to help.

To read some of the research abstracts related to some of the issues above, follow the links below

Dosage related bifidogenic effects of galacto- and fructo- oligosaccharides in formula-fed term infants. Moro G et.al.

Randomized double-blind study of the nutritional efficacy and bifidogenicity of a new infant formula containing partially hydrolysed protein, a high beta-palmitic acid level, and nondigestible oligosaccharides. Schmelzle H, et al.

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