The human microbiome, breast milk and autoimmunity

A fascinating study published in The American Journal of Clinical Nutrition illuminates how the microbiome of human breast milk changes depending on the mode of delivery (vaginal, elective and nonelective cesarean) and weight of the mother. This has great significance for the development of autoimmune and allergic diseases.To put the matter in context, consider also a paper recently published in Current Opinion in Rheumatology and describes how changes in the human microbiome can drive autoimmunity. The authors observe:

"Humans are superorganisms. The human body harbors an extensive microbiome, which has been shown to differ in patients with autoimmune diagnoses. Intracellular microbes slow innate immune defenses by dysregulating the vitamin D nuclear receptor, allowing pathogens to accumulate in tissue and blood. Molecular mimicry between pathogen and host causes further dysfunction by interfering with human protein interactions. Autoantibodies may well be created in response to pathogens."

Changes in the human microbiome can either promote or hinder immune system dysregulation and the process of molecular mimicry (cross-reaction between microbes and human tissues) that elicits autoimmune inflammation. The authors further state:

"The catastrophic failure of human metabolism observed in autoimmune disease results from a common underlying pathogenesis – the successive accumulation of pathogens into the microbiome over time, and the ability of such pathogens to dysregulate gene transcription, translation, and human metabolic processes. Autoimmune diseases are more likely passed in families because of the inheritance of a familial microbiome, rather than Mendelian inheritance of genetic abnormalities."

Bearing this in mind helps us appreciate the significance of the study on human breast milk. The authors were inspired by noting that...

"Breast milk is recognized as the most important postpartum element in metabolic and immunologic programming of health of neonates. The factors influencing the milk microbiome and the potential impact of microbes on infant health have not yet been uncovered...Our objective was to identify pre- and postnatal factors that can potentially influence the bacterial communities inhabiting human milk."

They examined the communities of microbes in breast milk at birth (colostrum within 2 days of birth, 1 month and 6 months after delivery) among women who varied in BMI, weight gain, and the mode of delivery. Also...

"...to shed light on the potential origin of the milk microbiome, its microbiota was compared with the available data for female skin, vaginal, oral cavity, fecal, and gut mucosal microbiota, including a total of 500,000 16S rRNA sequences."

This showed that the breast milk microbiome is different from the microbes in other parts of the body and is not simply a contaminant from the skin. The dynamism of the breast milk microbiome and its implications for autoimmunity shone through in their results for the several hundred species that are present:

"We found that the human milk microbiome changes over lactation. Weisella, Leuconostoc, Staphylococcus, Streptococcus, and Lactococcus were predominant in colostrum samples, whereas in 1- and 6-mo milk samples the typical inhabitants of the oral cavity (eg, Veillonella, Leptotrichia, and Prevotella) increased significantly. Milk from obese mothers tended to contain a different and less diverse bacterial community compared with milk from normal-weight mothers. Milk samples from elective but not from nonelective mothers who underwent cesarean delivery contained a different bacterial community than did milk samples from individuals giving birth by vaginal delivery, suggesting that it is not the operation per se but rather the absence of physiological stress or hormonal signals that could influence the microbial transmission process to milk."

Interestingly, the contents of the mother's intestines can contribute:

"Dendritic cells have been described to penetrate the intestinal epithelium to take up commensal bacteria from the gut lumen, to reach the systemic circulation, and to retain even live bacteria for several days; recently, the transfer of intestinal bacteria to the mammary glands within dendritic cells has been proposed."

The authors note the vital significance of the breast milk microbiome for the development of an infant's immune system:

"Prenatal and postnatal microbial exposures have profound effects on the microbial colonization of the intestine and maturation of the naive immune system. Given that the bacteria present in breast milk are among the very first microbes that enter the human body and given the vital role of bacteria in the infant’s physiology and development of the immune system, our data emphasize the necessity to understand the biological role that the breast milk microbiome could potentially play for human health. If the bacterial composition of human breast milk has coevolved to maximize the infant’s metabolic efficiency and to optimally stimulate the immune system, a skewed microbial milk composition might have important consequences for the infant’s health, and those potential consequences would need to be evaluated for future recommendations in child nutrition."

Clearly we are 'super organisms' consisting of a vast ocean of diverse DNA, and this is significantly influenced by the breast milk microbiome that is subject to change depending on time, metabolic status of the mother, and the mode of delivery.

"Our results indicate that milk bacteria are not contaminants and suggest that the milk microbiome is influenced by several factors that significantly skew its composition. Because bacteria present in breast milk are among the very first microbes entering the human body, our data emphasize the necessity to understand the biological role that the milk microbiome could potentially play for human health."

This is one of multiple factors that must be borne in mind by the clinician responsible for case management of autoimmune conditions.