Mucosal Immunity and Liver Metabolism in the Complex Condition of Lactation Insufficiency

Abstract

Lactation insufficiency is variously defined and includes the inability to produce milk, not producing enough milk to exclusively meet infant growth requirements, and pathological interruption of lactation (e.g., mastitis). Of women with intent-to-breastfeed, lactation insufficiency has been estimated to affect 38%–44% of newly postpartum women, likely contributing to the nearly 60% of infants that are not breastfed according to the World Health Organization’s guidelines. To date, research and clinical practice aimed at improving feeding outcomes have focused on hospital lactation support and education, with laudable results. However, researchers’ reports of recent rodent studies concerning fundamental lactation biology have suggested that the underlying pathologies of lactation insufficiency may be more nuanced than is currently appreciated. In this article, we identify mucosal biology of the breast and lactation-specific liver biology as two under-researched aspects of lactation physiology. Specifically, we argue that further scientific inquiry into reproductive state-dependent regulation of immunity in the human breast will reveal insights into novel immune based requirements for healthy lactation. Additionally, our synthesis of the literature supports the hypothesis that the liver is an essential player in lactation—highlighting the potential that pathologies of the liver may also be associated with lactation insufficiency. More research into these biologic underpinnings of lactation is anticipated to provide new avenues to understand and treat lactation insufficiency.

Reproductive state controls transcription in the murine liver, with implications for breast cancer liver metastasis

“…In sum, these transcriptional profile data are consistent with the need for increased functional output of the liver during lactation. Further, our data strengthen previous studies that defined the functional unit of lactation as including both the mammary gland and the liver 6,58 .…”

Measures of Maternal Metabolic Health as Predictors of Severely Low Milk Production

“…Elevated plasma triglycerides are also associated with suboptimal liver function and dysregulation of lipoprotein lipase, and it is recently postulated that these factors play key role in successful lactation. 50 As part of the low milk supply study, we isolated lactocyte mRNA from fresh milk, and in a subsequent report we will probe mammary gene expression signatures that may reveal how inflammation, lipid metabolism dysregulation, and insulin resistance contribute to severely impaired milk production.…”

Exploring the contribution of mammary-derived serotonin on liver and pancreas metabolism during lactation

“…The liver expresses the machinery necessary to synthesize, signal and metabolize serotonin which is known to regulate a variety of functions in liver biology such as tissue regeneration and hepatic blood flow [ 36 , 37 ]. It is also well accepted that the mammary gland and liver work as a functional unit during lactation by increasing the metabolic output needed to meet the nutritional demands [ 38 ]. Several lines of evidence in multiple species have indicated the liver is the primary source of glucose during lactation, although the regulation for this exact mechanism remains unknown [ 39 , 40 ].…”