The Gut‒Breast Axis: Programming Health for Life

The gut is a pivotal organ in health and disease. The events that take place in the gut during early life contribute to the programming, shaping and tuning of distant organs, having lifelong consequences. In this context, the maternal gut plays a quintessence in programming the mammary gland to face the nutritional, microbiological, immunological, and neuroendocrine requirements of the growing infant. Subsequently, human colostrum and milk provides the infant with an impressive array of nutrients and bioactive components, including microbes, immune cells, and stem cells. Therefore, the axis linking the maternal gut, the breast, and the infant gut seems crucial for a correct infant growth and development. The aim of this article is not to perform a systematic review of the human milk components but to provide an insight of their extremely complex interactions, which render human milk a unique functional food and explain why this biological fluid still truly remains as a scientific enigma.     

Brain–Gut–Microbiome Interactions and Intermittent Fasting in Obesity

The obesity epidemic and its metabolic consequences are a major public health problem both in the USA and globally. While the underlying causes are multifactorial, dysregulations within the brain–gut–microbiome (BGM) system play a central role. Normal eating behavior is coordinated by the tightly regulated balance between intestinal, extraintestinal and central homeostatic and hedonic mechanisms, resulting in stable body weight. The ubiquitous availability and marketing of inexpensive, highly palatable and calorie-dense food has played a crucial role in shifting this balance towards hedonic eating through both central (disruptions in dopaminergic signaling) and intestinal (vagal afferent function, metabolic toxemia, systemic immune activation, changes to gut microbiome and metabolome) mechanisms. The balance between homeostatic and hedonic eating behaviors is not only influenced by the amount and composition of the diet, but also by the timing and rhythmicity of food ingestion. Circadian rhythmicity affects both eating behavior and multiple gut functions, as well as the composition and interactions of the microbiome with the gut. Profound preclinical effects of intermittent fasting and time restricted eating on the gut microbiome and on host metabolism, mostly demonstrated in animal models and in a limited number of controlled human trials, have been reported. In this Review, we will discuss the effects of time-restricted eating on the BGM and review the promising effects of this eating pattern in obesity treatment.     

Postbiotic Supplementation for Children and Newborn’s Health

It is now well known how the microbiota can positively or negatively influence humans health, depending on its composition. The microbiota’s countless beneficial effects have allowed it to be defined as a genuine symbiont for our species. In an attempt to positively influence the microbiota, research has focused on probiotics and prebiotics. Probiotics are viable beneficial bacteria of various strains. Prebiotics are specific substances able to favor the development of advantageous bacteria strains. Postbiotics are a new category of compounds capable of affecting the microbiota. According to the different definitions, postbiotics include both nonviable bacteria and substances deriving from bacterial metabolism. Postbiotics are particularly promising in pediatric settings, as they offer some advantages over probiotics, including the absence of the risk of intestinal translocation or worsening of local inflammation. For these reasons, their use in fragile population categories such as newborns, and even more prematures, seems to be the best solution for improving microbiota’s health in this population. This narrative review aims to collect the research conducted so far on postbiotics’ potential in the first stages of life.     

Amino Acid Formula Containing Synbiotics in Infants with Cow’s Milk Protein Allergy: A Systematic Review and Meta-Analysis

Cow’s milk protein allergy (CMPA) is associated with dysbiosis of the infant gut microbiome, with allergic and immune development implications. Studies show benefits of combining synbiotics with hypoallergenic formulae, although evidence has never been systematically examined. This review identified seven publications of four randomised controlled trials comparing an amino acid formula (AAF) with an AAF containing synbiotics (AAF-Syn) in infants with CMPA (mean age 8.6 months; 68% male, mean intervention 27.3 weeks, n = 410). AAF and AAF-Syn were equally effective in managing allergic symptoms and promoting normal growth. Compared to AAF, significantly fewer infants fed AAF-Syn had infections (OR 0.35 (95% CI 0.19–0.67), p = 0.001). Overall medication use, including antibacterials and antifectives, was lower among infants fed AAF-Syn. Significantly fewer infants had hospital admissions with AAF-Syn compared to AAF (8.8% vs. 20.2%, p = 0.036; 56% reduction), leading to potential cost savings per infant of £164.05–£338.77. AAF-Syn was associated with increased bifidobacteria (difference in means 31.75, 95% CI 26.04–37.45, p < 0.0001); reduced Eubacterium rectale and Clostridium coccoides (difference in means −19.06, 95% CI −23.15 to −14.97, p < 0.0001); and reduced microbial diversity (p < 0.05), similar to that described in healthy breastfed infants, and may be associated with the improved clinical outcomes described. This review provides evidence that suggests combining synbiotics with AAF produces clinical benefits with potential economic implications.     

Do Gut Hormones Contribute to Weight Loss and Glycaemic Outcomes after Bariatric Surgery?

Bariatric surgery is an effective intervention for management of obesity through treating dysregulated appetite and achieving long-term weight loss maintenance. Moreover, significant changes in glucose homeostasis are observed after bariatric surgery including, in some cases, type 2 diabetes remission from the early postoperative period and postprandial hypoglycaemia. Levels of a number of gut hormones are dramatically increased from the early period after Roux-en-Y gastric bypass and sleeve gastrectomy—the two most commonly performed bariatric procedures—and they have been suggested as important mediators of the observed changes in eating behaviour and glucose homeostasis postoperatively. In this review, we summarise the current evidence from human studies on the alterations of gut hormones after bariatric surgery and their impact on clinical outcomes postoperatively. Studies which assess the role of gut hormones after bariatric surgery on food intake, hunger, satiety and glucose homeostasis through octreotide use (a non-specific inhibitor of gut hormone secretion) as well as with exendin 9–39 (a specific glucagon-like peptide-1 receptor antagonist) are reviewed. The potential use of gut hormones as biomarkers of successful outcomes of bariatric surgery is also evaluated.     

Effects of Bovine Colostrum with or without Egg on In Vitro Bacterial-Induced Intestinal Damage with Relevance for SIBO and Infectious Diarrhea

Small intestinal bacterial overgrowth (SIBO) occurs commonly, is difficult to treat, and frequently recurs. Bovine colostrum (BC) and chicken eggs contain immunoglobulins and other components that possess antimicrobial, immunoregulatory, and growth factor activities; however, it is not known if they have the ability to reduce injury caused by the presence of bacteria associated with SIBO (Streptococcus, Escherichia coli, Staphylococcus, Bacteroides, Klebsiella, Enterococcus, and Proteus) and infectious diarrhea (enteropathogenic Escherichia coli, Salmonella). We examined the effects of BC, egg, or the combination, on bacterial growth and bacteria-induced changes in transepithelial electrical resistance (TEER) and bacterial translocation across confluent Caco-2 monolayers. BC, egg, or the combination did not affect bacterial growth. Adding bacteria to monolayers reduced TEER and (with minor variations among species) increased bacterial translocation, increased monolayer apoptosis (increased caspase-3 and Baxα, reduced Bcl2), increased intercellular adhesion molecule 1 (ICAM-1), and reduced cell adhesion molecules zonulin1 (ZO1) and claudin-1. BC, egg, or the combination reduced these effects (all p < 0.01) and caused additional increases in vascular endothelial growth factor (VEGF) and Heat Shock Protein 70 (Hsp70) expression. We conclude that BC ± egg strengthens mucosal integrity against a battery of bacteria relevant for SIBO and for infectious diarrhea. Oral BC ± egg may have clinical value for these conditions, especially SIBO where eradication of precipitating organisms may be difficult to achieve.     

Vitamin D and Allergy Susceptibility during Gestation and Early Life

Worldwide, the prevalence of allergies in young children, but also vitamin D deficiency during pregnancy and in newborns is rising. Vitamin D modulates the development and activity of the immune system and a low vitamin D status during pregnancy and in early life might be associated with an increased risk to develop an allergy during early childhood. This review studies the effects of vitamin D during gestation and early life, on allergy susceptibility in infants. The bioactive form of vitamin D, 1,25(OH)2D, inhibits maturation and results in immature dendritic cells that cause a decreased differentiation of naive T cells into effector T cells. Nevertheless, the development of regulatory T cells and the production of interleukin-10 was increased. Consequently, a more tolerogenic immune response developed against antigens. Secondly, binding of 1,25(OH)2D to epithelial cells induces the expression of tight junction proteins resulting in enhanced epithelial barrier function. Thirdly, 1,25(OH)2D increased the expression of anti-microbial peptides by epithelial cells that also promoted the defense mechanism against pathogens, by preventing an invasive penetration of pathogens. Immune intervention by vitamin D supplementation can mitigate the disease burden from asthma and allergy. In conclusion, our review indicates that a sufficient vitamin D status during gestation and early life can lower the susceptibility to develop an allergy in infants although there remains a need for more causal evidence.     

The Effect of Dietary Fibre on Gut Microbiota,Lipid Profile,and Inflammatory Markers in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Background: A disequilibrium of the gut microbial community has been closely associated with systemic inflammation and metabolic syndromes including type 2 diabetes. While low fibre and high fat diets may lead to dysbiosis of the gut microbiome as a result of the loss of useful microbes, it has been reported that a high fibre diet may prevent the fermentation of protein and may promote eubiosis of gut microbiota. Aim: This review aims to evaluate the effect of dietary fibre (DF) on gut microbiota, lipid profile, and inflammatory markers in patients with type 2 diabetes. Methods: The PRISMA framework was relied on to conduct this systematic review and meta-analysis. Searches were carried out using electronic databases and reference list of articles. Results: Eleven studies were included in the systematic review, while ten studies were included in the meta-analysis. The findings revealed five distinct areas including the effects of DF on (a) gut microbiota (122 participants); (b) lipopolysaccharides (LPS, 79 participants) and lipopolysaccharides binding protein (LBP, 81 participants); (c) lipid profile; (d) inflammatory markers; and (e) body mass index (BMI, 319 participants). The relative abundance of Bifidobacterium increased by 0.73 (95% CI: 0.57, 0.89) in the DF group in contrast to the control (p < 0.05). With respect to LPS, the level was lower in the DF group than the control and the difference was significant (p < 0.05). The standardised mean difference for LPS was −0.45 (95% CI: −0.90, −0.01) although the difference between the two groups in relation to LBP was not significant (p = 0.08) and the mean difference was 0.92 (95% CI: −0.12, 1.95). While there was a decrease of −1.05 (95% CI: −2.07, −0.02) with respect to total cholesterol (356 participants) in the DF group as compared with the control (p < 0.05), both groups were not significantly different (p > 0.05) in the other lipid parameters. The difference between the groups was significant (p < 0.05) in relation to C-reactive protein, and the mean difference was 0.43 (95% CI: 0.02, 0.84). This could be due to the short duration of the included studies and differences in participants’ diets including the amount of dietary fibre supplements. However, the groups were not significantly different (p > 0.05) with respect to the other inflammatory markers. The meta-analysis of the BMI showed that the DF group decreased by −0.57 (95% CI: −1.02, −0.12) as compared with the control and this was significant (p < 0.01). Conclusion: DF significantly (p < 0.05) increased the relative abundance of Bifidobacterium and significantly decreased (p < 0.05) LPS, total cholesterol, and BMI as compared with the control. However, DF did not seem to have an effect that was significant on LBP, triglyceride, HDL cholesterol, LDL cholesterol, IL-6, TNF-α, adiponectin, and leptin. These findings have implications for public health in relation to the use of dietary fibre in nutritional interventions and as strategies for managing type 2 diabetes.     

Potential Role of Probiotics in Ameliorating Psoriasis by Modulating Gut Microbiota in Imiquimod-Induced Psoriasis-Like Mice

Psoriasis is an immune-mediated systemic disease that may be treated with probiotics. In this study, probiotic strains that could or could not decrease interleukin (IL)-17 levels were applied to imiquimod (IMQ)-induced psoriasis-like mice via oral administration. Bifidobacterium adolescentis CCFM667, B. breve CCFM1078, Lacticaseibacillus paracasei CCFM1074, and Limosilactobacillus reuteri CCFM1132 ameliorated psoriasis-like pathological characteristics and suppressed the release of IL-23/T helper cell 17 (Th17) axis-related inflammatory cytokines, whereas B. animalis CCFM1148, L. paracasei CCFM1147, and L. reuteri CCFM1040 neither alleviated the pathological characteristics nor reduced the levels of inflammatory cytokines. All effective strains increased the contents of short-chain fatty acids, which were negatively correlated with the levels of inflammatory cytokines. By performing 16S rRNA gene sequencing, the diversity of gut microbiota in psoriasis-like mice was found to decrease, but all effective strains made some specific changes to the composition of gut microbiota compared to the ineffective strains. Furthermore, except for B. breve CCFM1078, all other effective strains decreased the abundance of the family Rikenellaceae, which was positively correlated with psoriasis-like pathological characteristics and was negatively correlated with propionate levels. These findings demonstrated effects of strain-specificity, and how probiotics ameliorated psoriasis and provide new possibilities for the treatment of psoriasis.     

Gut Microbiota Prevents Sugar Alcohol-Induced Diarrhea

While poorly-absorbed sugar alcohols such as sorbitol are widely used as sweeteners, they may induce diarrhea in some individuals. However, the factors which determine an individual’s susceptibility to sugar alcohol-induced diarrhea remain unknown. Here, we show that specific gut bacteria are involved in the suppression of sorbitol-induced diarrhea. Based on 16S rDNA analysis, the abundance of Enterobacteriaceae bacteria increased in response to sorbitol consumption. We found that Escherichia coli of the family Enterobacteriaceae degraded sorbitol and suppressed sorbitol-induced diarrhea. Finally, we showed that the metabolism of sorbitol by the E. coli sugar phosphotransferase system helped suppress sorbitol-induced diarrhea. Therefore, gut microbiota prevented sugar alcohol-induced diarrhea by degrading sorbitol in the gut. The identification of the gut bacteria which respond to and degrade sugar alcohols in the intestine has implications for microbiome science, processed food science, and public health.