Protective effects of breastfeeding against urinary tract infection

LÅ Hanson

Department of Clinical Immunology, Göteborg University, Göteborg, Sweden

Hanson LÅ. Protective effects of breastfeeding against urinary tract infection. Acta Pædiatr 2004; 93: 154–156. Stockholm. ISSN 0803-5253 Protective factors in human milk act on mucosal membranes in the upper and lower respiratory tract and in the gastrointestinal tract. The way in which breastfeeding may reduce the risk of infections in a more remote site such as the urinary tract will be elucidated. Conclusion: The protective effect of breastfeeding on the urinary tract illustrates the complexity of the immune defence mechanisms responsible for such an action. Key words: Breastfeeding, urinary tract infection LÅ Hanson, Department of Clinical Immunology, Göteborg University, Guldhedsgatan 10, SE-413 46 Göteborg, Sweden (Tel. +46 31342 49 16, fax. +46 31 342 56 21, e-mail. Lars.a.hanson@immuno.gu.se)

As time has passed more and more well-designed studies with adequate statistical techniques have demonstrated that breastfeeding seems to protect against several forms of infection in the offspring (1). Usually it can be realized that the main protective factors of human milk function by preventing infectious agents from attacking the host via mucosal membranes. Thus, infections via the mucosae in the upper and lower respiratory tracts, e.g. otitis media, pneumonia and upper respiratory tract infections, are significantly reduced by breastfeeding (2–4); so too are infections via the intestinal mucosa, e.g. neonatal septicaemia and diarrhoea (5–7). But it is somewhat surprising that breastfeeding may also reduce the risk of infections at a more remote site such as the urinary tract. This seems to have been confirmed in a sizeable, prospective case–control study with elaborate statistical work-up, presented by Mårild et al. in this issue of Acta Pædiatrica (8).

It can be understood, however, how defence factors in the milk can prevent urinary tract infections (UTIs). Such infections are usually caused by facultative aerobic bacteria, which ascend from below and originate from the intestinal microflora. Those bacteria may have been coated by secretory immunoglobulin A (sIgA) antibodies from the milk in the breastfed child (9). This can presumably prevent them from reaching the urinary tract. These milk antibodies can bind to the bacteria owing to their antibody specificity, because they have been formed in the mammary glands by lymphocytes, which have migrated there from the lymphoid tissues in the mother’s gut (10). This is why the mother’s milk protects efficiently against her own intestinal flora, with which her baby should have been colonized, especially at birth, since the baby, like all newborn mammals, has been delivered next to the mother’s anus. The milk contains such antibodies against the mother’s intestinal microflora, as well as bacteria that she may have carried in the gut previously in life (11). This is presumably due to the fact that memory cells representing such earlier encounters are homing to her lactating mammary glands. In addition, the milk sIgA antibodies can bind to microbes such as Escherichia coli with type 1 pili, which attach to the carbohydrate moiety of the sIgA antibodies (12). Furthermore, breastfeeding seems to enhance type 1 piliation of E. coli in the gut, supporting the function of this defence mechanism (13). In agreement with this, IgA-deficient individuals less often carry type 1 piliated E. coli in the gut (14). Furthermore, a recent experimental study indicates that sIgA antibodies also may help microbes such as i.E. coli to form a biofilm on an epithelial layer, suggesting that establishment of a normal gut microflora may be promoted (15). Breastfeeding results in a stable enterobacterial flora with lower counts of enterobacteria than seen in bottle-fed infants. The E. coli of breastfed infants also carry fewer virulence factors, e.g. the K1 capsule, or resistance to the bactericidal effect of serum (16).

The mother’s milk has at least one additional component of apparent importance for protection of the urinary tract. As mentioned by Mårild et al. (8), human milk lactoferrin and fragments thereof come out in the urine of the breastfed infant (17). Lactoferrin, which is a major milk protein, not only efficiently kills various microbes, but does so without inducing inflammation. This takes place mainly by its capacity to block the transcription factor nuclear factor-κB in the nucleus, e.g. of cells in the innate immune system (18). As a consequence, the production of proinflammatory cytokines such as interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) and IL-6 is prevented. This kind of function seems to be a common theme in the antiinfectious capacities of human milk, including sIgA antibodies: to protect without inducing energy-costly, tissue-damaging and symptom-causing inflammation. Human lactoferrin, or certain microbicidal fragments thereof given orally, were shown to protect against experimental UTI caused by E. coli in mice (19). Such lactoferrin and fragments also significantly dampened the inflammation and course of experimental dextran sulfate-induced colitis in mice (20). Another such antiinfectious and non-inflammatory capacity of the milk is provided by its substantial fraction of oligosaccharides and glycoconjugates, functioning as receptor analogues for uropathogens, blocking their attachment to mucosal membranes, as mentioned by Mårild et al. (8). These components, as well as others in the maternal milk, affect the gut microflora, presumably making potential uropathogens less able to climb the urinary tract and establish infections. Some of these milk components even appear in the urine.

The authors found a significantly higher risk of acquisition of UTIs in non-breastfed than in breastfed children. This protection was strongly related to gender, in that the hazard ratio for girls was 3.78, but for boys 1.63. The reason for this is not clear, but could relate to the anatomical differences in the lower urinary tract between the genders. A similar observation was made recently for the protective capacity of breastfeeding against neonatal respiratory tract infections (21). Despite a detailed analysis, no obvious explanation could be given for the finding that good protection was seen in girls, but not in boys.

Mårild et al. note the prolonged protective effect against UTIs of breastfeeding after its termination (8). This is an interesting phenomenon, also suggested for several other infections, e.g. otitis media, upper and lower respiratory infections, diarrhoea, wheezing bronchitis and Haemophilus influenzae type b infections (1). The enhanced protective capacity has often been shown to last for some years and is now understood to occur via several mechanisms. Anti-idiotypic antibodies in the milk may prime the breastfed infant to a more efficient response of the idiotype, e.g. against poliovirus (22). Lymphocytes in the milk can be taken up by the offspring and are capable of priming the child’s immune system. Numerous other factors in the milk, recently summarized (11), may add to these effects, e.g. the cytokine IL-7, which promotes the development of the Peyer’s patches and the cryptopatches in the gut mucosa, enhancing specifically the production of Tγδ cells (23). It is likely that the numerous factors in human milk that seem actively to enhance various functions in the breastfed offspring may help in the understanding of some of the long-term effects of breastfeeding (1, 11).

The study by Mårild et al. is an interesting illustration of how the results of a careful clinical study can be put in the perspective of ongoing research in several fields, helping researchers to realize the enormous complexity of the many mechanisms involved. Despite this complexity, the basic knowledge is continuously expanding and becoming useful at the clinical level.

References

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Received Oct. 30, 2003; accepted Oct. 30, 2003