and differentially affect gut microbes and metabolites in mice with Treg deficiency.

Treg deficiency causes a lethal, CD4 T cell-driven autoimmune disease called IPEX syndrome (immunodysregulation, polyendocrinopathy, and enteropathy, with X-linked inheritance) in humans and in the scurfy (SF) mouse, a mouse model of the disease. Feeding DSM 17938 (LR 17938, LR) to SF mice reprograms the gut microbiota, reduces disease progression, and prolongs lifespan. However, the efficacy and mechanism of LR, compared with other probiotics, in producing these effects is unknown.

Antibiotic-modulated microbiome suppresses lethal inflammation and prolongs lifespan in Treg-deficient mice.

Background: Regulatory T cell (Treg) deficiency leads to IPEX syndrome, a lethal autoimmune disease, in Human and mice. Dysbiosis of the gut microbiota in Treg-deficient scurfy (SF) mice has been described, but to date, the role of the gut microbiota remains to be determined.

Results: To examine how antibiotic-modified microbiota can inhibit Treg deficiency-induced lethal inflammation in SF mice, Treg-deficient SF mice were treated with three different antibiotics.

Human Breast Milk Promotes the Immunomodulatory Function of Probiotic DSM 17938 in the Neonatal Rat Intestine.

Background And Objective: Breast milk has many growth-promoting and immune-active components, including transforming growth factor-β, lactoferrin, lysozyme, immunoglobulin A, and prebiotics such as the human milk oligosaccharides. Treatment with DSM 17938 (LR), a probiotic with immunomodulatory functions, significantly increases regulatory T cells (Tregs) in the intestinal mucosa of newborn suckling rats. In humans, treatment with LR of infants with colic reduces crying optimally if the infants are breast-fed.

DSM 17938 feeding of healthy newborn mice regulates immune responses while modulating gut microbiota and boosting beneficial metabolites.

Early administration of DSM 17938 (LR) prevents necrotizing enterocolitis and inhibits regulatory T-cell (Treg)-deficiency-associated autoimmunity in mice. In humans, LR reduces crying time in breastfed infants with colic, modifies severity in infants with acute diarrheal illnesses, and improves pain in children with functional bowel disorders. In healthy breastfed newborns with evolving microbial colonization, it is unclear if early administration of LR can modulate gut microbiota and their metabolites in such a way as to promote homeostasis.

Reduces the Severity of Experimental Autoimmune Encephalomyelitis in Mice by Modulating Gut Microbiota.

The gut microbiome plays an important role in immune function and has been implicated in multiple sclerosis (MS). However, how and if the modulation of microbiota can prevent or treat MS remain largely unknown. In this study, we showed that probiotic DSM 17938 () ameliorated the development of murine experimental autoimmune encephalomyelitis (EAE), a widely used animal model of MS, a model which is primarily mediated by T17 and T1 cells.

Infant Colic Represents Gut Inflammation and Dysbiosis.

Objective: To dissect potential confounding effects of breast milk and formula feeding on crying + fussing, fecal calprotectin, and gut microbiota in babies with colic. We hypothesized that infant colic is associated with gut inflammation linked to intestinal dysbiosis.

Study Design: A nested case-control design of 3 of our studies was used to analyze clinical and laboratory data at presentation, comparing babies with colic with controls.

Protective effect of Lactobacillus reuteri DSM 17938 against experimental necrotizing enterocolitis is mediated by Toll-like receptor 2.

Lactobacillus reuteri DSM 17938 (LR 17938) has been shown to reduce the incidence and severity of necrotizing enterocolitis (NEC). It is unclear if preventing NEC by LR 17938 is mediated by Toll-like receptor 2 (TLR2), which is known to mediate proinflammatory responses to bacterial cell wall components. NEC was induced in newborn TLR2 or wild-type (WT) mice by the combination of gavage-feeding cow milk-based formula and exposure to hypoxia and cold stress.

Adenosine A Receptor Deletion Blocks the Beneficial Effects of in Regulatory T-Deficient Scurfy Mice.

The lack of a functional Foxp3 transcription factor and regulatory T (Treg) cells causes lethal, CD4 T cell-driven autoimmune diseases in scurfy (SF) mice and humans. Recent studies have shown that adenosine A receptor activation limits inflammation and tissue damage, thereby playing an anti-inflammatory role. However, the role of the adenosine A receptor in the development of disease in SF mice remains unclear.

Lactobacillus reuteri for Infants with Colic: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial.

Objective: To assess the safety of probiotic Lactobacillus reuteri strain Deutsche Sammlung von Mikroorganismen (DSM) 17938 with daily administration to healthy infants with colic and to determine the effect of L reuteri strain DSM 17938 on crying, fussing, inflammatory, immune, and microbiome variables.

Study Design: We performed a controlled, double-blinded, phase 1 safety and tolerability trial in healthy breast-fed infants with colic, aged 3 weeks to 3 months, randomly assigned to L reuteri strain DSM 17938 (5 × 10 colony-forming units daily) or placebo for 42 days and followed for 134 days.

Results: Of 117 screened infants, 20 were randomized to L reuteri strain DSM 17938 or placebo (sunflower oil) (in a 2:1 ratio) with 80% retention.

Resetting microbiota by Lactobacillus reuteri inhibits T reg deficiency-induced autoimmunity via adenosine A2A receptors.

Regulatory T (T reg) cell deficiency causes lethal, CD4 T cell-driven autoimmune diseases. Stem cell transplantation is used to treat these diseases, but this procedure is limited by the availability of a suitable donor. The intestinal microbiota drives host immune homeostasis by regulating the differentiation and expansion of T reg, Th1, and Th2 cells.

Circulating L-selectin expressing-T cell subsets correlate with the severity of Foxp3 deficiency autoimmune disease.

L-selectin (CD62L) is normally highly expressed in naïve T cells. The expression levels of CD62L have been reported to be decreased on T cells during the inflammatory state. It is currently unknown whether the frequency of CD62L T cell subsets in the peripheral blood can be used as a marker to indicate is disease severity during inflammation.