A high fiber diet or supplementation with Lactococcus lactis subspecies cremoris to pregnant mice confers protection against intestinal injury in adult offspring.

The diet during pregnancy, or antenatal diet, influences the offspring's intestinal health. We previously showed that antenatal butyrate supplementation reduces injury in adult murine offspring with dextran sulfate sodium (DSS)-induced colitis. Potential modulators of butyrate levels in the intestine include a high fiber diet or dietary supplementation with probiotics. To test this, we supplemented the diet of pregnant mice with high fiber, or with the probiotic bacteria Lactococcus lactis subspecies cremoris or Lactobacillus rhamnosus GG. We then induced chronic colitis with DSS in their adult offspring. We demonstrate that a high fiber antenatal diet, or supplementation with Lactococcus lactis subspecies cremoris during pregnancy diminished the injury from DSS-induced colitis in offspring. These data are evidence that antenatal dietary interventions impact offspring gut health and define the antenatal diet as a therapeutic modality to enhance offspring intestinal health.

Probiotics for prevention of necrotizing enterocolitis: Where do we stand?

In this review, we provide a historical perspective on probiotic use in preterm infants. We review recent data on the treatment effects of probiotics on necrotizing enterocolitis, sepsis, and mortality. We highlight guidance statements from professional societies and organizations, discussing key points within the context of the currently available evidence from both randomized trials and cohort studies. Finally, we summarize experiences from several North American centers that have reported on the routine use of probiotics, including our center. Our goal is to highlight some of the considerations and complexities surrounding routine probiotics use in preterm infants.

Butyrate supplementation to pregnant mice elicits cytoprotection against colonic injury in the offspring.

BACKGROUND: Maternal diet during pregnancy can impact progeny health and disease by influencing the offspring's gut microbiome and immune development. Gut microbial metabolism generates butyrate, a short-chain fatty acid that benefits intestinal health. Here we assess the effects of antenatal butyrate on the offspring's gastrointestinal health. We hypothesized that antenatal butyrate supplementation will induce protection against colitis in the offspring. METHODS: C57BL/6 mice received butyrate during pregnancy and a series of experiments were performed on their offspring. RNA sequencing was performed on colonic tissue of 3-week-old offspring. Six-8-week-old offspring were subjected to dextran sulfate sodium-induced colitis. Fecal microbiome analysis was performed on the 6-8-week-old offspring. RESULTS: Antenatal butyrate supplementation dampened transcript enrichment of inflammation-associated colonic genes and prevented colonic injury in the offspring. Antenatal butyrate increased the offspring's stool microbiome diversity and expanded the prevalence of specific gut microbes. CONCLUSIONS: Antenatal butyrate supplementation resulted in downregulation of genes in the offspring's colon that function in inflammatory signaling. In addition, antenatal butyrate supplementation was associated with protection against colitis and an expanded fecal microbiome taxonomic diversity in the offspring. IMPACT: Dietary butyrate supplementation to pregnant mice led to downregulation of colonic genes involved in inflammatory signaling and cholesterol synthesis, changes in the fecal microbiome composition of the offspring, and protection against experimentally induced colitis in the offspring. These data support the mounting evidence that the maternal diet during pregnancy has enduring effects on the offspring's long-term health and disease risk. Although further investigations are needed to identify the mechanism of butyrate's effects on fetal gut development, the current study substantiates the approach of dietary intervention during pregnancy to optimize the long-term gastrointestinal health of the offspring.

Lactobacillus rhamnosus GG Orchestrates an Antitumor Immune Response.

BACKGROUND & AIMS: In colorectal cancer, approximately 95% of patients are refractory to immunotherapy because of low antitumor immune responses. Therefore, there is an exigent need to develop treatments that increase antitumor immune responses and decrease tumor burden to enhance immunotherapy. METHODS: The gut microbiome has been described as a master modulator of immune responses. We administered the human commensal, Lactobacillus rhamnosus GG (LGG), to mice and characterized the changes in the gut immune landscape. Because the presence of lactobacilli in the gut microbiome has been linked with decreased tumor burden and antitumor immune responses, we also supplemented a genetic and a chemical model of murine intestinal cancer with LGG. For clinical relevance, we therapeutically administered LGG after tumors had formed. We also tested for the requirement of CD8 T cells in LGG-mediated modulation of gut tumor burden. RESULTS: We detected increased colonic CD8 T-cell responses specifically in LGG-supplemented mice. The CD8 T-cell induction was dependent on dendritic cell activation mediated via Toll-like receptor-2, thereby describing a novel mechanism in which a member of the human microbiome induces an intestinal CD8 T-cell response. We also show that LGG decreased tumor burden in the murine gut cancer models by a CD8 T-cell-dependent manner. CONCLUSIONS: These data support the potential use of LGG to augment antitumor immune responses in colorectal cancer patients and ultimately for increasing the breadth and efficacy of immunotherapy.

Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) is an inflammatory disease affecting premature infants. Intestinal microbial composition may play a key role in determining which infants are predisposed to NEC and when infants are at highest risk of developing NEC. It is unclear how to optimize antibiotic therapy in preterm infants to prevent NEC and how to optimize antibiotic regimens to treat neonates with NEC. This article discusses risk factors for NEC, how dysbiosis in preterm infants plays a role in the pathogenesis of NEC, and how probiotic and antibiotic therapy may be used to prevent and/or treat NEC and its sequelae.

At the heart of microbial conversations: endocannabinoids and the microbiome in cardiometabolic risk.

Cardiometabolic syndrome encompasses intertwined risk factors such as hypertension, dyslipidemia, elevated triglycerides, abdominal obesity, and other maladaptive metabolic and inflammatory aberrations. As the molecular mechanisms linking cardiovascular disease and metabolic disorders are investigated, endocannabinoids have emerged as molecules of interest. The endocannabinoid system (ECS) of biologically active lipids has been implicated in several conditions, including chronic liver disease, osteoporosis, and more recently in cardiovascular diseases. The gut microbiome is a major regulator of inflammatory and metabolic signaling in the host, and if disrupted, has the potential to drive metabolic and cardiovascular diseases. Extensive studies have unraveled the impact of the gut microbiome on host physiology, with recent reports showing that gut microbes exquisitely control the ECS, with significant influences on host metabolic and cardiac health. In this review, we outline how modulation of the gut microbiome affects host metabolism and cardiovascular health via the ECS, and how these findings could be exploited as novel therapeutic targets for various metabolic and cardiac diseases.

Multicenter retrospective comparison of spontaneous intestinal perforation outcomes between primary peritoneal drain and primary laparotomy.

PURPOSE: The purpose of our study was to compare outcomes of infants with spontaneous intestinal perforation (SIP) treated with primary peritoneal drain versus primary laparotomy. METHODS: We performed a multi-institution retrospective review of infants with diagnosis of SIP from 2012 to 2016. Clinical characteristics and outcomes were compared between infants treated with primary peritoneal drain vs infants treated with laparotomy. RESULTS: We identified 171 patients treated for SIP (drain n = 110 vs. laparotomy n = 61). There were no differences in maternal or prenatal characteristics. There were no clinically significant differences in vital signs, white blood cell or platelet measures, up to 48 h after intervention. Patients who were treated primarily with a drain were more premature (24.9 vs. 27.2 weeks, p < 0.001) and had lower median birth weight (710 g vs. 896 g, p < 0.001). No significant differences were found in complications, time to full feeds, length of stay (LOS) or mortality between the groups. Primary laparotomy group had more procedures (median number 1 vs. 2, p = 0.002). There were 32 (29%) primary drain failures whereby a laparotomy was ultimately needed. CONCLUSIONS: SIP treated with primary drain is successful in the majority of patients with no significant differences in outcomes when compared to laparotomy with stoma. THE LEVEL OF EVIDENCE: III.

To start or not: Factors to consider when implementing routine probiotic use in the NICU.

Supplementation of probiotics to very low birth weight (VLBW) infants has been extensively studied, with multiple meta-analyses reporting probiotics decrease the risk of necrotizing enterocolitis (NEC) and death. Despite availability of this evidence, the decision to initiate routine probiotic supplementation to preterm infants continues to be a complex one. There are uncertainties regarding the use of probiotics, including selecting the appropriate product, dose and target population. Additionally, availability of specific probiotic products and regulatory oversight varies by country, raising concerns regarding the safety and efficacy of specific probiotic products. In this review, we summarize the latest evidence on probiotic use in preterm infants and discuss considerations that may help guide clinicians who are considering routine probiotic supplementation.