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SummaryHuman milk contains large quantities of iron-binding protein, of which the greater proportion is lactoferrin, though small amounts of transferrin are also present. Three samples of human milk with unsaturated ironbinding capacities of between 56 and 89% had a powerful bacteriostatic effect on Escherichia coli 0lll/B4. The bacteriostatic properties of milk were abolished if the iron-binding proteins were saturated with iron. Purified human lactoferrin, in combination with specific E. coli antibody, strongly inhibited the growth of E. coli, and this effect was also abolished by saturating the lactoferrin with iron.Guinea-pig milk also contains lactoferrin and transferrin. Newly born guinea-pigs fed on an artificial diet and dosed with E. coli 0111 had higher counts of E. coli 0111 in the intestine than suckled animals. The apparent supressive effect of guinea-pig milk on E. coli in the intestine could be reversed by feeding the iron compound haematin. It seems that iron-binding proteins in milk may play an important part in resistance to infantile enteritis caused by E. coli. the same serotypes can be isolated from healthy infants (Thomson, Watkins, and Gray, 1956).If breast-feeding confers resistance to E. coli it is obviously important to know what factors are involved. Ross and Dawes (1954) and C. L. Bullen and Willis (1971) suggested that the predominance of Lactobacillus bifidus, which is associated with a low pH in the faeces of breast-fed infants, may be related to the suppression of E. coli in the intestine. It seems highly probable that this system makes an important contribution to resistance, especially in the large intestine. However, our experiments show that human milk can have a specific inhibitory effect on E. coli. Human milk contains large quantities of ironbinding protein, of which the greater proportion is lactoferrin, though small amounts of transferrin are also present (Masson and Heremans, 1971). We have evidence to suggest that lactoferrin, in combination with specific antibody to E. coli, is responsible for the bacteriostatic effect. These results are supported by experiments in guinea-pigs, which produce a milk with fairly high concentrations of lactoferrin, but rather more transferrin than human milk. These studies strongly suggest that the iron-binding proteins of milk may play an important part in resistance to E. coli infection, and this particularly applies to conditions in the small intestine.

Bacterial resistance to antibiotics is a major threat to clinical medicine. However, natural resistance to bacterial infection, which does not depend on antibiotics, is a powerful protective mechanism common to all mankind. The availability of iron is the heart of the matter and the successful functioning of these antibacterial systems depends entirely upon an extremely low level of free ionic iron (10(-18) M) in normal tissue fluids. This in turn depends on well-oxygenated tissues where the oxidation-reduction potential (Eh) and pH control the binding of iron by unsaturated transferrin and lactoferrin. Bacterial virulence is greatly enhanced by freely available iron, such as that in fully-saturated transferrin or free haemoglobin. Following trauma a fall in tissue Eh and pH due to ischaemia, plus the reducing powers of bacteria, can make iron in transferrin freely available and abolish the bactericidal properties of tissue fluids with disastrous results for the host. Hyperbaric oxygen is a possible therapeutic measure that could restore normal bactericidal systems in infected tissues by raising the Eh and pH.