Microbes central to human reproduction

As studies uncover the breadth of microbes associated with human life, opportunities will emerge to manipulate and augment their functions in ways that improve health and longevity. From involvement in the complexities of reproduction and fetal/infant development, to delaying the onset of disease, and indeed countering many maladies, microbes offer hope for human well-being. Evidence is emerging to suggest that microbes may play a beneficial role in body sites traditionally viewed as being sterile. Although further evidence is required, we propose that much of medical dogma is about to change significantly through recognition and understanding of these hitherto unrecognized microbe–host interactions. A meeting of the International Scientific Association for Probiotics and Prebiotics held in Aberdeen, Scotland (June 2014), presented new views and challenged established concepts on the role of microbes in reproduction and health of the mother and infant. This article summarizes some of the main aspects of these discussions

Lactation and neonatal nutrition: defining and refining the critical questions.

This paper resulted from a conference entitled "Lactation and Milk: Defining and refining the critical questions" held at the University of Colorado School of Medicine from January 18-20, 2012. The mission of the conference was to identify unresolved questions and set future goals for research into human milk composition, mammary development and lactation. We first outline the unanswered questions regarding the composition of human milk (Section I) and the mechanisms by which milk components affect neonatal development, growth and health and recommend models for future research. Emerging questions about how milk components affect cognitive development and behavioral phenotype of the offspring are presented in Section II. In Section III we outline the important unanswered questions about regulation of mammary gland development, the heritability of defects, the effects of maternal nutrition, disease, metabolic status, and therapeutic drugs upon the subsequent lactation. Questions surrounding breastfeeding practice are also highlighted. In Section IV we describe the specific nutritional challenges faced by three different populations, namely preterm infants, infants born to obese mothers who may or may not have gestational diabetes, and infants born to undernourished mothers. The recognition that multidisciplinary training is critical to advancing the field led us to formulate specific training recommendations in Section V. Our recommendations for research emphasis are summarized in Section VI. In sum, we present a roadmap for multidisciplinary research into all aspects of human lactation, milk and its role in infant nutrition for the next decade and beyond

Impact of 2′-fucosyllactose on gut microbiota composition in adults with chronic gastrointestinal conditions: batch culture fermentation model and pilot clinical trial findings

Intestinal dysbiosis has been described in patients with certain gastrointestinal conditions including irritable bowel syndrome (IBS) and ulcerative colitis. 2′-fucosyllactose (2′-FL), a prebiotic human milk oligosaccharide, is considered bifidogenic and butyrogenic. To assess prebiotic effects of 2′-FL, alone or in combination with probiotic strains (potential synbiotics), in vitro experiments were conducted on stool from healthy, IBS, and ulcerative colitis adult donors. In anaerobic batch culture fermenters, Bifidobacterium and Eubacterium rectale-Clostridium coccoides counts, and short-chain fatty acids (SCFAs) including butyrate increased during fermentation with 2′-FL and some of the 2′-FL/probiotic combinations. In a subsequent open-label pilot trial, the effect of a 2′-FL-containing nutritional formula was evaluated in twelve adults with IBS or ulcerative colitis. Gastrointestinal Quality of Life Index (GIQLI) total and gastrointestinal symptoms domain scores, stool counts of Bifidobacterium and Faecalibacterium prausnitzii, and stool SCFAs including butyrate, increased after six weeks of intervention. Consistent with documented effects of 2′-FL, the batch culture fermentation experiments demonstrated bifidogenic and butyrogenic effects of 2′-FL during fermentation with human stool samples. Consumption of the 2′-FL-containing nutritional formula by adults with IBS or ulcerative colitis was associated with improvements in intra- and extra-intestinal symptoms, and bifidogenic and butyrogenic effects

Local and systemic effects of bioactive food ingredients: is there a role for functional foods to prime the gut for resilience?

Scientific advancements in understanding the impact of bioactive components in foods on the gut microbiota and wider physiology create opportunities for designing targeted functional foods. The selection of bioactive ingredients with potential local or systemic effects holds promise for influencing overall well-being. An abundance of studies demonstrate that gut microbiota show compositional changes that correlate age and disease. However, navigating this field, especially for non-experts, remains challenging, given the abundance of bioactive ingredients with varying levels of scientific substantiation. This narrative review addresses the current knowledge on the potential impact of the gut microbiota on host health, emphasizing gut microbiota resilience. It explores evidence related to the extensive gut health benefits of popular dietary components and bioactive ingredients, such as phytochemicals, fermented greens, fibres, prebiotics, probiotics, and postbiotics. Importantly, this review distinguishes between the potential local and systemic effects of both popular and emerging ingredients. Additionally, it highlights how dietary hormesis promotes gut microbiota resilience, fostering better adaptation to stress—a hallmark of health. By integrating examples of bioactives, this review provides insights to guide the design of evidence-based functional foods aimed at priming the gut for resilience

In vivo and in vitro models of intestinal intraepithelial lymphocyte development

Intestinal intraepithelial lymphocytes (IELs) make up a vast, but poorly understood population of lymphocytes. Located between epithelial cells that line the gut, they may provide a first line of defense against invading pathogens. Intriguingly, the largest population of IELs, TCRγδ+CD8αα + T cells, appears to be extrathymically derived. A more complete understanding of the origin of these cells may lead to a better understanding of their function. We, therefore, have utilized both in vivo and in vitro experimental systems to investigate IEL development. In vivo, the absence of IL-2, in IL-2 deficient (IL-2−/− ) mice, leads to reduced TCRγδ+CD8αα + IELs. Additionally, this reduction in TCRγδ+ IELs is not secondary to the colitis seen in IL-2−/− mice, as it is also present in gnotobiotic IL-2−/− mice. Furthermore, hematopoietic progenitor cells from IL-2 −/− bone marrow have an intrinsic defect in their ability to regenerate TCRγδ+ IELs after transfer to irradiated, CD45 congenic recipients. IL-2, therefore, appears to play an important role in IEL development. Given the limitations of using in vivo systems to dissect IEL development, in addition to the possibility that intestinal epithelial cells may play a key role in promoting IEL development, we have developed an in vitro model. A culture system has been developed in which freshly isolated small intestinal epithelial cells are cultured with hematopoietic progenitor enriched bone marrow cells. Preliminary experiments reveal that after 30 days of co-culture clusters of cells can be seen in close contact with the epithelial cell layer. These clusters appear to be negative for the expression of such lymphoid specific genes as RAG, Ets-1, AIOLOS and GATA-3. After relocation of the laboratory to the United Kingdom, primary IEC cultures were not re-established. Further experimentation needs to be conducted in order to confirm that IEC can support IEL development. The in vitro model system will provide a useful tool for further study of IEL development

In vivo and in vitro models of intestinal intraepithelial lymphocyte development

Intestinal intraepithelial lymphocytes (IELs) make up a vast, but poorly understood population of lymphocytes. Located between epithelial cells that line the gut, they may provide a first line of defense against invading pathogens. Intriguingly, the largest population of IELs, TCRγδ+CD8αα + T cells, appears to be extrathymically derived. A more complete understanding of the origin of these cells may lead to a better understanding of their function. We, therefore, have utilized both in vivo and in vitro experimental systems to investigate IEL development. In vivo, the absence of IL-2, in IL-2 deficient (IL-2−/− ) mice, leads to reduced TCRγδ+CD8αα + IELs. Additionally, this reduction in TCRγδ+ IELs is not secondary to the colitis seen in IL-2−/− mice, as it is also present in gnotobiotic IL-2−/− mice. Furthermore, hematopoietic progenitor cells from IL-2 −/− bone marrow have an intrinsic defect in their ability to regenerate TCRγδ+ IELs after transfer to irradiated, CD45 congenic recipients. IL-2, therefore, appears to play an important role in IEL development. Given the limitations of using in vivo systems to dissect IEL development, in addition to the possibility that intestinal epithelial cells may play a key role in promoting IEL development, we have developed an in vitro model. A culture system has been developed in which freshly isolated small intestinal epithelial cells are cultured with hematopoietic progenitor enriched bone marrow cells. Preliminary experiments reveal that after 30 days of co-culture clusters of cells can be seen in close contact with the epithelial cell layer. These clusters appear to be negative for the expression of such lymphoid specific genes as RAG, Ets-1, AIOLOS and GATA-3. After relocation of the laboratory to the United Kingdom, primary IEC cultures were not re-established. Further experimentation needs to be conducted in order to confirm that IEC can support IEL development. The in vitro model system will provide a useful tool for further study of IEL development

Modulation of Toll-like receptor-stimulated dendritic cell cytokine production by exogenous osteopontin. (98.32)

Abstract Osteopontin (OPN) is a pleiotropic cytokine produced by mast cells, macrophages, activated T cells, NK T cells and dendritic cells and is present at high levels in human milk. Several studies in OPN-deficient mice have suggested a role for OPN in the development of Th1 and Th17 mediated immune responses. Dendritic cells (DC) are central regulators of T helper cell responses, however, it is unknown whether exogenous OPN supplied by milk plays a role in the differentiation of DC upon activation by signals through the TLRs. To address this question, we assessed the role of OPN in the LPS and CpG induced cytokine responses in bone marrow derived dendritic cells (BMDC). In the presence of OPN, the production of LPS and CpG stimulated IL-10, IL-6 and TNFα by BMDC was reduced in a dose dependent manner. OPN had no effect on LPS or CpG stimulated IL-12p40 or IL-12p70 production. OPN by itself did not induce IL-12p40, IL-12p70, IL-10, IL-6 or TNFα production by BMDC. These data suggest that exogenous OPN can modulate dendritic cell responses to TLR stimulation, and suggest a mechanism by which orally ingested OPN might influence the function of the intestinal immune system. Further studies are required to determine whether T helper cell polarization is affected by OPN treatment of BMDC, as well as to determine if exogenous OPN has similar inhibitory effects on cytokine production by tissue derived DC.</jats:p

Effect of a Nutrition Support Formula in Adults With Inflammatory Bowel Disease: A Pilot Study.

BACKGROUND: Due to the high prevalence of nutrient deficiencies in patients with inflammatory bowel disease (IBD), routine monitoring of nutrient status and supplementation are recommended. OBJECTIVE: This preliminary study was implemented to prospectively identify potential effects of a nutrition support formula on blood nutrient parameters in adults with IBD. METHODS: Ten adults with Crohns disease or ulcerative colitis were recruited from the Portland, Oregon, metropolitan area into a single-arm, open-label pilot study. Participants consumed a nutrition support beverage twice daily for 12 weeks. The formula contained a mixture of micronutrients (including methylated forms of folate and vitamin B12), macronutrients, and phytonutrients (including curcumin, xanthohumol, ginger compounds, and quercetin). Primary measures were the following parameters: folate, vitamin B12, red blood cell (RBC) count, hemoglobin, hematocrit, electrolytes, and albumin. Exploratory measures included a food frequency questionnaire, circulating blood cell counts, and inflammatory markers. RESULTS: Nine participants completed the study and one withdrew. Adherence was 98%. Serum folate increased 48.7% (P = .029), serum vitamin B12 increased 17.4% but did not reach statistical significance (P = .053), and red cell distribution width (RDW) decreased 9.2% (P = .012) over the 12-week study period. There were minimal shifts in total white blood cell (WBC) counts (-1.0%, P = .845), but percent neutrophils decreased 10.4% (P = .042) and absolute lymphocyte count increased 18.6% (P = .048). RBC count, hemoglobin, hematocrit, electrolytes, albumin, and inflammatory markers did not change significantly. Post hoc analysis demonstrated that neutrophil-lymphocyte ratio (NLR) decreased 18.4% (not significant, P = .061). CONCLUSION: Serum folate and RDW improved in adults with IBD after 12 weeks. Modulation of leukocyte subtypes was also observed, including a decrease in neutrophils and an increase in lymphocytes, with no change in total WBC count. A randomized, controlled study to further examine effects of the nutrition support formula will be initiated to follow up on this promising, but preliminary investigation