Human milk fatty acid profile across lactational stages after term and preterm delivery: A pooled data analysis.

BACKGROUND: Lipids in human milk (HM) provide the majority of energy for developing infants, as well as crucial essential fatty acids (FA). The FA composition of HM is highly variable and influenced by multiple factors. We sought to increase understanding of the variation in HMFA profiles and their development over the course of lactation, and after term and preterm delivery, using a pooled data analysis. OBJECTIVE: To review the literature and perform a pooled data analysis to qualitatively describe an extensive FA profile (36 FAs) in term and preterm colostrum, transitional - and mature milk up to 60 days postpartum. DESIGN: A Medline search was conducted for HMFA profile data following term or preterm delivery. The search was confined to English language papers published between January 1980 and August 2018. Studies reporting original data, extensive FA profiles in HM from healthy mothers were included. Weighted least squares (WLS) means were calculated from the pooled data using random or fixed effect models. RESULTS: Our pooled data analysis included data from 55 studies worldwide, for a total of 4374 term milk samples and 1017 preterm milk samples, providing WLS means for 36 FAs. Patterns in both term and preterm milk were apparent throughout lactation for some FAs: The most abundant FAs (palmitic, linoleic and oleic acid) remained stable over time, whereas several long-chain polyunsaturated FAs (including ARA and DHA) seemed to decrease and short- and medium-chain FAs increased over time. CONCLUSIONS: High heterogeneity between individual studies was observed for the reported levels of some FAs, whereas other FAs were remarkably consistent between studies. Our pooled data suggests that specific FA categories fluctuate according to distinct patterns over the course of lactation; many of these patterns are comparable between term and preterm milk.

Effects of deoxycholate on human colon cancer cells: apoptosis or proliferation.

BACKGROUND: Deoxycholic acid has long been attributed as a tumour promoter in the colon. It exerts its growth-related actions in a phorbol ester-like manner, by stimulating protein kinase C. The aim of this study was to investigate the effect of deoxycholic acid on proliferation and apoptosis in the colon, by exposing colon cancer cells to it in increasing concentrations. METHODS: Human colon cancer cells (Caco-2 and HT-29) were treated with deoxycholate or its two structural isomers, 3-beta-12-alpha-dihydroxy-5-beta-cholan-24-oic acid and 3-alpha-12-beta-dihydroxy-5-beta-cholan-24-oic acid. Proliferation was evaluated by cell counting, and apoptosis by estimating percentage cell survival and assessment of nuclear morphology. RESULTS: Within the concentration range of up to 20 microM, deoxycholate stimulated growth of both human colon cancer cell lines. Its growth-promoting effect was abolished after inhibition of protein kinase C. At concentrations above 100 microM, deoxycholate induced apoptosis in both cell lines. Epimers of deoxycholate were significantly less potent in stimulating growth. CONCLUSION: Low-dose deoxycholate stimulates colon cancer cell proliferation while > 100 micromol L(-1) of this secondary bile acid induces apoptosis in colon cancer cells. Deoxycholate might promote the likelihood of malignant transformation by increasing epithelial cell turnover in the colon.

Deoxycholic acid stimulates migration in colon cancer cells.

BACKGROUND: Deoxycholic acid and other secondary bile acids have long been considered tumour promoters in the colon. However, their effect on cell migration, known to play an important role in colon carcinogenesis, has not been studied so far. OBJECTIVE: To investigate the possible effects of deoxycholic acid on colon cancer-cell migration in culture. METHODS: Human colon carcinoma cells (Caco-2) were seeded on basement membrane matrix. To evaluate replication-blocked cell migration, we wounded confluent monolayers of cells with a sterile scalpel, and inhibited cell replication with mitomycin C. Immediately after wounding, the cells were exposed to 0-100 micromol/l deoxycholic acid. Migration over 72 h was monitored using a phase contrast microscope. RESULTS: Replication-blocked migration was stimulated by deoxycholic acid in a dose-dependent manner, with the maximum effect at 20 micromol/l deoxycholic acid. Enhancement of migration rate was unaffected by immunoneutralization of transforming growth factor beta (a known migration-promoting peptide). However, specific inhibition of protein kinase C markedly inhibited deoxycholic acid-induced Caco-2 cell migration. CONCLUSION: In addition to its well-established role in the enhancement of proliferation, deoxycholic acid also stimulates colon cancer-cell migration along the basement membrane matrix. The mechanism of this stimulation is likely to involve protein kinase C. Deoxycholic acid-stimulated migration might additionally contribute to the tumour-promoting effects of secondary bile acids in the colon.

Interactions between laminin and epithelial cells in intestinal health and disease.

Laminins are a multigene family of extracellular matrix molecules. Quantitatively, they are one of the most abundant glycoproteins present in basement membranes. Functionally, they can modulate several key biological activities, including cell adhesion and migration, gene expression and cell survival. Variability in the spatial and temporal expression of laminins, as well as of their specific receptors of the integrin family, in various tissues and organs, suggests that different laminins perform distinct functions. This article focuses on the human intestinal epithelium as a paradigm to illustrate the potential relationship between laminin-cell interactions and the cell state. This rapidly renewing epithelium consists of spatially separated proliferative and differentiated cell populations located in the crypts and on the villi, respectively. Differential distributions of the various laminins and laminin-binding integrins have been observed along the crypt-villus axis in both the developing and the adult intestine, and important alterations in the pattern of laminin expression have been reported in various intestinal pathologies, such as tufting enteropathy, Crohn's disease and ulcerative colitis, and colorectal cancer. More-direct approaches, including experimentation with in vitro and in vivo models, have provided evidence in support of a role for laminins in intestinal cell functions. Although further work is still needed, laminins emerge more and more as key regulators of specific cell functions important in both intestinal health and intestinal disease.

Effect of structural analogues of propionate and butyrate on colon cancer cell growth.

The aim of this study was to evaluate the effects of natural short-chain fatty acids (butyrate, propionate, valerate, acetate) and structural analogues of butyrate and propionate on cell growth and apoptosis in three human colonic adenocarcinoma cell lines (HT-29, Colo-320, and SW-948). We have previously shown that mercapto- and bromo-analogues of butyrate and propionate compete with natural short-chain fatty acids for uptake in the colonocyte. Among naturally occurring short-chain fatty acids, butyrate was the most potent inhibitor of proliferation in all three cell lines. Propionate exhibited a weaker antiproliferative effect, while other short-chain fatty acids (valerate, acetate) were ineffective. Bromo-analogues of butyrate and propionate were more potent proapoptotic agents than butyrate. In contrast to butyrate, the analogues induced strand breaks on isolated supercoiled DNA, the effect being completely reversed by a DNA-protecting agent, spermine. We conclude that bromo-analogues of butyrate and propionate are more potent proapoptotic agents than butyrate in colon cancer cells in culture. Their effect may be a result of direct DNA damage.