Babies fed on mother's milk are known to have fewer medical problems than babies fed mother's milk substitutes. In particular, breast-fed babies suffer fewer infections than babies that are not breast-fed.
In many mammals, mortality is high immediately after parturition and among the newborn. For example, 20 percent of pigs do not survive the first week of life. Approximately one-half of that number die due to gastrointestinal disorders caused by pathogenic strains of one or more bacteria. Further, gastrointestinal disorders contribute to poor growth in many pigs that survive the first week.
The frequency of diarrheal deaths in British infants in 1960 was six times greater for those infants fed cow's milk than those who were breast-fed. [Goldman et al., J. Pediatr., 82:1082 (1979)]In 1979, the incidence of enteric infections was found to be lowest in breast-fed infants in countries where sanitary conditions are poor. [Kabara, Nutrition Reviews, 38:65 (1980)]Whether the above statistics are due to a protective factor in human milk or whether human milk conveys fewer pathogenic organisms has not been determined. [Kabara above; Welsh, J. Pediatr., 94:1 (1979)]
A recent report by Koopman et al., Am. J. Public Health, May 1985, compared data on 143 babies with gastrointestinal illness and 143 babies free of such illness. Their case-control study indicated that babies fed on formula were at 6 times the risk of babies on breast milk and 2.5 times the risk of babies on cows'milk.
Among those substances in human milk reported to provide anti-infective properties are a growth enhancer for lactobacillus, an antistaphlococcal agent, immunoglobulins, complement components, lysozyme, lactoperoxidose, lactoferrin, macrophages, lymphocytes and lipids (Kabara, above). However, whether these factors protect the mammary gland from infection or confer infection resistance on the child is unknown (Kabara, above).
The gut of the breast-fed human infant is enriched with lactobacilli in comparison to the gut of infants who are not breast-fed. This difference has been attributed to a lactobacillus growth factor and the high concentration of lactose in human milk, along with its low bulk, low protein content and low buffering capacity. It has been postulated that the high lactose concentration allows sufficient lactose to pass to the intestine to support the growth of lactose fermenters that produce acid conditions and encourage lactobacilli. The large population of lactobacilli alters growth conditions in the gut creating an environment in which diarrhea-producing organisms are less likely to grow (Welsh, above).
Other possible sources of resistance to enteric infections have not been definitively demonstrated. IgA has been thought to be protective (Welsh, above). Complement is thought to be insignificant because human milk heated to 56.degree. C. for thirty minutes retains its antibacterial activity, and that temperature is normally sufficient to inactivate complement.
Studies indicate that milk, particularly human milk, contains lipids thought to account for antimicrobial activity. Data are reported to indicate a strong correlation between microbial resistance and the level of lipase and monoglycerides (Kabara, above). Further, very short chain fatty acids, that is C.sub.6 or less, affect gram-negative organisms, the organisms that frequently are responsible for enteric infections.
Kabara et al., Antimicrob. Aq. Chemother. 2:23. (1972) advocate adding monoglycerides to improve the lipid formulation of synthetic or animal milk and artificial feeds for human infants and other young mammals to provide the food with more antimicrobial activity as is usually found in human milk.
Kabara et al., above, report several generalities regarding the bacteriostatic activity of fatty acids. Of tested straight chain saturated fatty acids, lauric acid (C.sub.12) was reported to have the most bacteriostatic activity on gram-positive organisms. Bacteriostatic activity reportedly increased with the addition of one and two double bonds to the fatty acid chain, but a third unsaturation was not as effective. A free carboxyl group was reported to be necessary for activity. Esters reportedly had decreased activity.
However, reduction of the carboxyl group to an aldehyde or alcohol, and changing that group into an amide or amine reportedly increased bacteriostatic effects. Further, in contrast to the other derivatives, amines were active against both gram-positive and gram-negative organisms. Specifically, the addition of monolaurin to milk substitutes and animal feed was advocated to provide the best overall antimicrobial activity.
Investigators have also studied the effect of lipid, and in particular, gangliosides, on the body's response to bacteria or bacterial toxins.
Ganglioside fraction GM1 (monosialoganglioside) is considered to be the cell membrane receptor for heat-labile enterotoxins of Escherichia coli (E. coli) and Vibrio cholerae [Olsvik et al., NIPH Ann., 6:5, (1983)]. Immunogenicity studies in rabbits indicated that gangliosides inhibited the primary and secondary immune responses to a common bacterial antigen as measured by hemagglutinin levels. However, gangliosides did not inhibit attachment of the antigen to red blood cells or alter the antigenic determinants. Agarwal et al. J. Immun., 107:1448, (1970) concluded gangliosides were an immunosuppressant.
Otaness et al. Infect. Immun., 40:563. (1983) studied the inhibition of E. coli and Vibrio cholerae enterotoxins by the ganglioside fraction of human milk. They reported that the enterotoxin inhibitor in human milk appeared to be gangliosides, and in particular ganglioside fraction GM1. They concluded that human milk gangliosides may be important in protecting infants against enterotoxin-induced diarrhea at the cell membrane receptor-toxin interaction level, rather than by an effect upon the bacteria themselves.
It would be advantageous to find a substance in human milk that protects the infant from the microorganisms that cause enteric infections, and to use that substance as an additive to milk substitutes for young mammals. It would be particularly desirable to find a relatively more available source of such a substance than human milk that functions protectively in a manner similar to human milk, and that can be added to mother's milk substitutes to enhance the resistance of a young mammal to enteric infections.