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Background Infantile colic is a common problem during the first three months of life. This randomized, double-blind, placebo-controlled trial conducted in an urban hospital in Delhi, India evaluated the efficacy and safety of oral lactase in management of infantile colic. Methods One hundred sixty-two clinically healthy infants aged < 5 months age [mean (SD) = 63.5 (30.5) days] fulfilling the Rome-IV diagnostic criteria for infantile colic were enrolled. Eligible children were randomly allocated to receive 5 drops of lactase (600 FCC units/mL) ( n  = 80) or placebo ( n  = 82) mixed with breast milk or formula feed four times a day for a duration of 4 weeks. Primary outcomes were duration of crying or fussing (min/d), and number of days with colic lasting > 3 h/d; secondary outcomes were parental satisfaction and adverse events. Results At the end of four weeks, mean (SD) crying or fussing time (min/d) was significantly shorter in infants receiving lactase in comparison to placebo [89.9 (115.2) vs .178.5 (153.2); P  = 0.001]. The mean (SD) number of days with colic was also significantly less in the lactase group as compared to placebo group at the end of the treatment [12.1 (7.8) vs 17.6 (8.4); P  < 0.001]. By the end of 4 th week, parental satisfaction in terms of infant’s mood, activity, alertness, comfort and oral intake was better in intervention group. The adverse event profile was comparable between two groups. Conclusions Oral lactase treatment in infantile colic results in symptomatic relief in terms of shortening of duration of crying or fussing, and better parental satisfaction. Trial registration Clinical trial registry of India (CTRI/2017/12/010930) registered on 20/12/2017.

Maldigestion occurs when digestive enzymes are lacking to help break complex food components into absorbable nutrients within the gastrointestinal tract. Education is needed to help patients manage the intricacies of digestive enzyme replacement therapies and ensure their effectiveness in reducing symptoms of maldigestion.

Although infantile colic is considered to be a self-limiting and benign condition, it is often a frustrating problem for parents and caregivers. It is a frequent source of consultation with healthcare professionals and is associated with high levels of parental stress and anxiety.1,2 Several published reviews of the literature have explored dietary, pharmacological, complementary and behavioural therapies as options for the management of infantile colic.1,3 Here, we assess whether these management options are supported by the literature and if there are any novel treatment options.

C.H., a three-and-a-half-year-old Caucasian boy, was admitted for a routine respite stay at a pediatric palliative care hospice in the fall of 2006. CH. was born with complex congenital anomalies including pontine dysplasia, optic pituitary dysplasia, central diabetes insipidus, adrenal insufficiency, hypothyroidism, epilepsy, and gastric dumping syndrome associated with hypoglycemia. In 2004, a fundoplication procedure had been performed to manage his severe gastroesophageal reflux disease.

Functional gastrointestinal symptoms are frequent, and may be driven by several pathogenic mechanisms. Symptoms may persist in lactose intolerant (LI) patients (i.e., subjects with intestinal lactase deficiency, lactose malabsorption producing symptoms), after a lactose-free diet. Our hypothesis was that probiotic and vitamin B6 treatment may be useful to alleviate symptoms in LI patients through a positive modulation of gut microbial composition and relative metabolism. We aimed to test the efficacy of a novel formulation of Bifidobacterium longum BB536 and Lactobacillus rhamnosus HN001 plus vitamin B6 (ZR) in 23 LI subjects with persistent symptoms during a lactose-free diet. Symptoms, microbiome, and metabolome were measured at baseline and after 30 days in a crossover, randomized, double-blind study of ZR versus placebo (PL). Compared with PL, the administration of probiotics and vitamin B6 significantly decreased bloating (p = 0.028) and ameliorated constipation (p = 0.045). Fecal microbiome differed between ZR and PL. ZR drove the enrichment of several genera involved in lactose digestion including Bifidobacerium. Moreover, the relative abundance of acetic acid, 2-methyl-propanoic acid, nonenal, and indolizine 3-methyl increased, while phenol decreased. Our findings highlight the importance of selected probiotics and vitamin B6 to alleviate symptoms and gut dysbiosis in lactose intolerant patients with persistent functional gastrointestinal symptoms.

Dendritic cells (DCs) have a role in the development and activation of self-reactive pathogenic T cells 1 , 2 . Genetic variants that are associated with the function of DCs have been linked to autoimmune disorders 3 , 4 , and DCs are therefore attractive therapeutic targets for such diseases. However, developing DC-targeted therapies for autoimmunity requires identification of the mechanisms that regulate DC function. Here, using single-cell and bulk transcriptional and metabolic analyses in combination with cell-specific gene perturbation studies, we identify a regulatory loop of negative feedback that operates in DCs to limit immunopathology. Specifically, we find that lactate, produced by activated DCs and other immune cells, boosts the expression of NDUFA4L2 through a mechanism mediated by hypoxia-inducible factor 1α (HIF-1α). NDUFA4L2 limits the production of mitochondrial reactive oxygen species that activate XBP1-driven transcriptional modules in DCs that are involved in the control of pathogenic autoimmune T cells. We also engineer a probiotic that produces lactate and suppresses T cell autoimmunity through the activation of HIF-1α–NDUFA4L2 signalling in DCs. In summary, we identify an immunometabolic pathway that regulates DC function, and develop a synthetic probiotic for its therapeutic activation. Lactate produced by dendritic cells (DCs) suppresses T-cell-mediated autoimmunity through a mechanism in which lactate activates HIF-1α–NDUFA4L2 signalling in DCs and thereby limits DC-mediated pro-inflammatory responses such as the development of encephalitogenic T cells.

BACKGROUND: Lactose intolerance (LI) is a common medical problem with limited treatment options. The primary symptoms are abdominal pain, diarrhea, bloating, flatulence, and cramping. Limiting dairy foods to reduce symptoms contributes to low calcium intake and the risk for chronic disease. Adaptation of the colon bacteria to effectively metabolize lactose is a novel and potentially useful approach to improve lactose digestion and tolerance. RP-G28 is novel galacto-oligosaccharide (GOS) being investigated to improve lactose digestion and the symptoms of lactose intolerance in affected patients. METHODS: A randomized, double-blind, parallel group, placebo-controlled study was conducted at 2 sites in the United States. RP-G28 or placebo was administered to 85 patients with LI for 35 days. Post-treatment, subjects reintroduced dairy into their daily diets and were followed for 30 additional days to evaluate lactose digestion as measured by hydrogen production and symptom improvements via a patient-reported symptom assessment instrument. RESULTS: Lactose digestion and symptoms of LI trended toward improvement on RP-G28 at the end of treatment and 30 days post-treatment. A reduction in abdominal pain was also demonstrated in the study results. Fifty percent of RP-G28 subjects with abdominal pain at baseline reported no abdominal pain at the end of treatment and 30 days post treatment (p = 0.0190). RP-G28 subjects were also six times more likely to claim lactose tolerance post-treatment once dairy foods had been re-introduced into their diets (p = 0.0389). CONCLUSIONS: Efficacy trends and favorable safety/tolerability findings suggest that RP-G28 appears to be a potentially useful approach for improving lactose digestion and LI symptoms. The concurrent reduction in abdominal pain and improved overall tolerance could be a meaningful benefit to lactose intolerant individuals. STUDY REGISTRATION: ClinicalTrials.gov NCT01113619 .

Lactase (LCT) deficiency affects approximately 75% of the world's adult population and may lead to lactose malabsorption and intolerance. Currently, the regulation of LCT gene expression remains poorly known. Peroxisome proliferator activator receptorγ (PPARγ) is a key player in carbohydrate metabolism. While the intestine is essential for carbohydrate digestion and absorption, the role of PPARγ in enterocyte metabolic functions has been poorly investigated. This study aims at characterizing PPARγ target genes involved in intestinal metabolic functions. In microarray analysis, the LCT gene was the most upregulated by PPARγ agonists in Caco‐2 cells. We confirmed that PPARγ agonists were able to increase the expression and activity of LCT both in vitro and in vivo in the proximal small bowel of rodents. The functional response element activated by PPARγ was identified in the promoter of the human LCT gene. PPARγ modulation was able to improve symptoms induced by lactose‐enriched diet in weaned rats. Our results demonstrate that PPARγ regulates LCT expression, and suggest that modulating intestinal PPARγ activity might constitute a new therapeutic strategy for lactose malabsorption.

Background Irritable bowel syndrome symptoms are associated with diverse pathophysiological mechanisms including small intestinal bacterial overgrowth and food intolerance. Small intestinal bacterial overgrowth leads to the decreased activity of several digestive enzymes, including lactase. Aims To assess the efficacy of rifaximin-alpha on the symptoms and lactase activity of patients with irritable bowel syndrome without constipation. Methods This was a prospective, pilot study. The recruited patients had irritable bowel syndrome without constipation (Rome IV criteria), a positive lactulose-Hydrogen Breath Test for small intestinal bacterial overgrowth, low urinary D-Xylose levels measured using the Lactest® test, and self-reported lactose intolerance. In addition, lactose HBT was performed. All patients received 400 mg rifaximin-alpha every 8 h for 2 weeks. Four weeks after the intervention, lactose and lactulose HBT were performed, and the symptoms and urinary D-Xylose levels were evaluated. Results After treatment with rifaximin-alpha, 60% of the patients reported improvement in abdominal pain, 44% in bloating, 36% in flatulence, 60% in borborygmi, and 72% in stool consistency. A negative lactulose-Hydrogen Breath Test result for SIBO was documented in 32% of patients, and lactose maldigestion by lactose-Hydrogen Breath Test was reduced from 88 to 52% of the studied subjects. The median D-Xylose levels before and after treatment were 7.6 (IQR 4.34–13.7) mg/dL vs. 10.4 (IQR 7.1–17.3) mg/dL, p  = 0.002. Conclusions Rifaximin-alpha caused symptomatic improvement, reduced lactose maldigestion, and reduced positive Hydrogen Breath Test results for small intestinal bacterial overgrowth in patients with irritable bowel syndrome without constipation.

Lactose intolerance (LI) is characterized by the presence of primarily gastrointestinal clinical signs resulting from colonic fermentation of lactose, the absorption of which is impaired due to a deficiency in the lactase enzyme. These clinical signs can be modified by several factors, including lactose dose, residual lactase expression, concurrent ingestion of other dietary components, gut-transit time, and enteric microbiome composition. In many of individuals with lactose malabsorption, clinical signs may be absent after consumption of normal amounts of milk or, in particular, dairy products (yogurt and cheese), which contain lactose partially digested by live bacteria. The intestinal microbiota can be modulated by biotic supplementation, which may alleviate the signs and symptoms of LI. This systematic review summarizes the available evidence on the influence of prebiotics and probiotics on lactase deficiency and LI. The literature search was conducted using the MEDLINE (via PUBMED) and SCOPUS databases following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and included randomized controlled trials. For each study selected, the risk of bias was assessed following the Cochrane Collaboration methodology. Our findings showed varying degrees of efficacy but an overall positive relationship between probiotics and LI in relation to specific strains and concentrations. Limitations regarding the wide heterogeneity between the studies included in this review should be taken into account. Only one study examined the benefits of prebiotic supplementation and LI. So further clinical trials are needed in order to gather more evidence.