Hydrolyzed Protein Formula Research Articles

Hydrolyzed protein formula improves the nutritional tolerance by increasing intestinal development and altering cecal microbiota in low-birth-weight piglets.

Prematurity or low birth weight (LBW), poses a significant challenge in global health. Exploring appropriate and effective nutritional interventions is crucial for the growth and development of LBW infants. Hydrolyzed protein formula has been suggested as a potential solution to prevent intestinal dysfunction and improve digestion and absorption in infants. This study aimed to investigate the benefits of hydrolyzed protein formula on feeding intolerance, intestinal morphological development, and microbiota in a LBW piglet model. A total of 24 male piglets (3 d of age, 0.95-1.25 kg average BW) were assigned (8 pens/diet; 1 pigs/pen) into three dietary treatments and fed with a basic formula (BF), standard premature infant formula (SF) and hydrolyzed protein formula (HF) respectively, for 7 d. After the piglets sacrifice, growth performance, amino acid metabolism and intestinal morphology were assessed. 16S rRNA sequencing and microbial metabolic phenotypes analyzed the effects of different formula treatments on intestinal flora structure of LBW piglets. The HF diet reduced the rates of diarrhea and milk vomiting were reduced by 20.44% (p > 0.05) and 58.44% (p > 0.05), and decreased the crypt depth in the ileum while increasing the ratio of villus height/crypt depth and the mRNA expressions of y+LAT1 and b0,+AT in the ileum (p < 0.05). HF increased the final body weight, serum Thr and essential amino acid contents, and CAT2 and b0,+AT mRNA expressions in ileal mucosa compared with the SF diet (p < 0.05). Microbiota sequencing results showed that the colonic microbial richness indices (Chao1, ACE, and observed species), the diversity indices (Shannon and Simpson), and the phyla Actinobacteriota, unidentified_Bacteria, Acidobacteriota and Actinobacteria, the genus Rubrobacter and RB41 were reduced (p < 0.05) in SF and HF groups. Microbial metabolic phenotypes analysis showed a reduction in the richness of biofilm-forming bacteria (p < 0.05). In summary, hydrolyzed protein formula had better nutrition and tolerance in LBW suckling piglets by improving amino acid transport and intestinal development, and regulating gut microbial communities.

Glutamic acid intake by formula-fed infants: are acceptable daily intakes appropriate?

The 2017 European Food Safety Authority (EFSA) recommendation of an acceptable daily intake (ADI) of 30 mg glutamic acid/kg bw/day did not take into consideration the primary energy sources during infancy, including infant formulas. In the present study, we determined total daily intakes of glutamic acid in a contemporary cohort of healthy infants who were fed either cow milk formula (CMF) or extensive protein hydrolysate formula (EHF); the formulas differed substantially in glutamic acid content. The infants (n = 141) were randomized to be fed either CMF or EHF. Dietary intakes were determined from weighed bottle methods and/or prospective diet records, and body weights were measured on 14 occasions from 0.5 to 12.5 months. Secondary data analysis determined the glutamic acid content of the diet over time. The trial was registered at http://www.clinicaltrials.gov/ as NCT01700205, 3 October 2012. Glutamic acid intake from formula and other foods was significantly higher in infants fed EHF when compared to CMF. As glutamic acid intake from formula decreased, intake from other nutritional sources steadily increased from 5.5 months. Regardless of formula type, every infant exceeded the ADI of 30 mg/kg bw/day from 0.5 to 12.5 months. Conclusion: Given that the ADI recommendation was not based on actual intake data of primary energy sources during infancy, the present findings on the growing child’s ingestion of glutamic acid from infant formula and the complementary diet may be of interest when developing future guidelines and communications to parents, clinical care providers, and policy makers.What is Known:• The 2017 re-evaluation of the safety of glutamic acid-glutamates and the recommended acceptable daily intake (ADI) of 30 mg/kg bw/d by the European Food Safety Authority (EFSA) did not include actual intake data of the primary energy sources during infancy.What is New:• During the first year, glutamic acid intake from infant formula and other food sources exceeded the ADI of 30 mg/kg bw/day.

Infant behavioral state and stool microbiome in infants receiving Lactocaseibacillus rhamnosus GG in formula: randomized controlled trial

BackgroundOur aim was to evaluate infant behavioral state, stool microbiome profile and calprotectin in infants with infantile colic receiving a partially hydrolyzed protein formula with or without added Lacticaseibacillus (formerly Lactobacillus) rhamnosus GG (LGG).MethodsIn this single-center, double-blind, controlled, parallel, prospective study, term infants (14–28 days of age) identified with colic (using modified Wessel’s criteria: cried and/or fussed ≥ 3 h/day for ≥ 3 days/week, in a one-week period) were randomized to receive one of two formulas over a three-week feeding period: marketed partially hydrolyzed cow’s milk-based infant formula (PHF, n = 35) or a similar formula with added LGG (PHF-LGG, n = 36). Parent-reported infant behavior was recorded at three time points (Study Days 2–4, 10–12, and 18–20). Duration (hours/day) of crying/fussing (averaged over each three-day period) was the primary outcome. Stool samples were collected at Baseline and Study End (Days 19–21) to determine stool LGG colonization (by qPCR) and microbial abundance (using 16S rRNA gene sequencing) and calprotectin (μg/g).ResultsDuration of crying/fussing (mean ± SE) decreased and awake/content behavior increased over time with no significant group differences over the course of the study. There were no group differences in the percentage of infants who experienced colic by study end. Colic decreased by Study End vs Baseline in both groups. Change in fecal calprotectin also was similar between groups. Comparing Study End vs Baseline, LGG abundance was greater in the PHF-LGG group (P < 0.001) whereas alpha diversity was greater in the PHF group (P = 0.022). Beta diversity was significantly different between PHF and PHF-LGG at Study End (P = 0.05). By study end, relative abundance of L. rhamnosus was higher in the PHF-LGG vs PHF group and vs Baseline.ConclusionsIn this pilot study of infants with colic, both study formulas were well tolerated. Crying/fussing decreased and awake/content behavior increased in both study groups over the course of the study. Study results demonstrate a successful introduction of the probiotic to the microbiome. The partially hydrolyzed protein formula with added LGG was associated with significant changes in the gut microbiome.Trial registrationClinicalTrials.gov, ClinicalTrials.gov Identifier: NCT02340143. Registered 16/01/2015.

Softer More Frequent Stools in Infants With Difficult Stooling Fed Hydrolyzed Protein Formula With Added Prebiotics: Randomized Controlled Trial.

ObjectiveTo evaluate stool consistency in infants with reported hard or infrequent stools fed hydrolyzed protein formula with added prebiotics designed to promote stool softening.MethodsIn this multi-center, double-blind, controlled study, eligible infants (28–300 days of age at enrollment) were randomized to: partially hydrolyzed cow’s milk protein formula (PHF, 75% carbohydrate as lactose; 12 mg Mg/100 kcal; n = 49) or routine intact protein cow’s milk-based infant formula (Control, 92% carbohydrate as lactose; 8 mg Mg/100 kcal; n = 51) over a 14-day period. Both formulas had a prebiotic blend (polydextrose and galactooligosaccharides, 4 g/L; 1:1 ratio). Parent-reported stool consistency (hard = 1 through watery = 5) and other daily outcomes were collected by diary. Endpoint stool consistency (mean score over last 3 days of study feeding) was the primary outcome. Adverse events were recorded.ResultsBaseline stool consistency (Control: 1.4 ± 0.1, PHF: 1.4 ± 0.1) and frequency were similar between groups; the majority had hard (n = 61, 64%) or formed (n = 30, 32%) stools. Stool consistency became softer over Day 1–3 (Control: 2.5 ± 0.1, PHF: 2.6 ± 0.1) and remained similar from Day 4 to 6 through study end (post hoc analysis). For PHF vs Control, endpoint stool consistency was significantly softer (3.4 ± 0.1 vs 3.0 ± 0.1; P = 0.019) and frequency significantly higher (1.5 ± 0.1 vs 1.0 ± 0.1; P = 0.002). Crying, fussing, and appearance of pain during stooling decreased from baseline to study end in both groups. Formula intake, infant fussiness and incidence of adverse events were similar between groups.ConclusionAn infant formula designed to promote stool softening was well-tolerated and associated with softer, more frequent stools in infants with reported hard or infrequent stools.

The Macronutrient Composition of Infant Formula Produces Differences in Gut Microbiota Maturation That Associate with Weight Gain Velocity and Weight Status.

This proof-of-principle study analyzed fecal samples from 30 infants who participated in a randomized controlled trial on the effects of the macronutrient composition of infant formula on growth and energy balance. In that study, infants randomized to be fed cow milk formula (CMF) had faster weight-gain velocity during the first 4 months and higher weight-for-length Z scores up to 11.5 months than those randomized to an isocaloric extensive protein hydrolysate formula (EHF). Here we examined associations among infant formula composition, gut microbial composition and maturation, and children’s weight status. Fecal samples collected before and monthly up to 4.5 months after randomization were analyzed by shotgun metagenomic sequencing and targeted metabolomics. The EHF group had faster maturation of gut microbiota than the CMF group, and increased alpha diversity driven by Clostridia taxa. Abundance of Ruminococcus gnavus distinguished the two groups after exclusive feeding of the assigned formula for 3 months. Abundance of Clostridia at 3–4 months negatively correlated with prior weight-gain velocity and body weight phenotypes when they became toddlers. Macronutrient differences between the formulas likely led to the observed divergence in gut microbiota composition that was associated with differences in transient rapid weight gain, a well-established predictor of childhood obesity and other comorbidities.

Effect of prophylactic use of hydrolyzed protein formula on gastrointestinal diseases and physical growth in preterm infants: a Meta analysis.

To systematically evaluate the effect of prophylactic use of hydrolyzed protein formula on gastrointestinal diseases and physical development in preterm infants. A computerized search was performed in the databases including China National Knowledge Infrastructure, Wanfang Data, Weipu, PubMed, Embase, and the Cochrane Library to identify randomized controlled trials of the effect of prophylactic use of hydrolyzed protein formula on gastrointestinal diseases and physical growth in preterm infants. RevMan 5.3 software was used to perform a Meta analysis for the included studies. A total of 7 randomized controlled studies were included. The results of Meta analysis showed that compared with the whole protein formula, the prophylactic use of hydrolyzed protein formula could reduce the risk of neonatal necrotizing enterocolitis (RR=0.40, P=0.04) and feeding intolerance (RR=0.40, P=0.005), and had no significant effect on the growth of weight, length and head circumference (P>0.05). Compared with the whole protein formula, the prophylactic use of hydrolyzed protein formula in preterm infants may reduce the occurrence of necrotizing enterocolitis and feeding intolerance, and can meet the nutrient requirement of physical development. However, the evidence is limited, and the results of this study cannot support the routine prophylactic use of hydrolyzed protein formula in preterm infants.

A partially hydrolyzed formula with synbiotics supports adequate growth and is well tolerated in healthy, Chinese term infants: A double-blind, randomized controlled trial

ObjectivesThe aim of this study was to evaluate growth and gastrointestinal tolerance in infants fed a partially hydrolyzed protein formula (pHF) with a synbiotic mixture of short-chain galacto-oligosaccharides and long-chain fructooligosaccharides (scGOS/lcFOS; 9:1) and Bifidobacterium breve M-16V (test formula) compared with an intact protein infant formula (IF) with scGOS/lcFOS (control formula). MethodsThis randomized, double-blind, controlled, multicenter trial enrolled healthy, fully formula-fed Chinese infants (≤44 d) who received either the test (n = 112) or control formula (n = 112) until 17 wk of age. Fully breastfed infants served as a reference (n = 60). Anthropometrics, gastrointestinal symptoms, and adverse events were assessed monthly. Primary outcome was weight gain in grams per day from baseline to 17 wk of age. ResultsEquivalence in daily weight gain (primary outcome) was demonstrated between the test and control groups (estimated mean difference [SE]: –0.36 [0.93] g/d, 90% confidence interval [CI], –1.90 to 1.18) as well as between each IF group and the breastfed reference group (test: 0.02 [1.05] g/d, 90% CI, –1.71 to 1.75; control: 0.36 [1.04] g/d, 90% CI, –1.35 to 2.08). There were no clinically relevant differences in gastrointestinal tolerance or adverse events between the formula groups. ConclusionA pHF with synbiotics supports adequate growth and is well tolerated in healthy, term-born Chinese infants. Additionally, infant growth and gastrointestinal tolerance measures of both IF groups were comparable to the breastfed group and can be considered suitable and well tolerated for use.

Novel Dietary Fiber Blend Alters Metabolism of Gastrointestinal Microbiome to Improve Digestive Health and Produce Beneficial Postbiotics in Adult Cats

The feline gastrointestinal (GI) microbiome is capable of fermenting a variety of plant fibers. Addition of dietary fibers from select plant sources may promote improvements in feline GI health. A novel fiber blend was prepared with pecan shells, flaxseed, beet pulp, citrus pulp & crushed cranberries.16 adult cats were assigned to group 1 & fed a control food (CF1): hydrolyzed protein formula without the novel fiber blend during a 3 week pre-feed, then switched to a test food (TF1): hydrolyzed protein formula with the novel fiber blend for 3 weeks (CF1: 3850 kcal/kg, 0.7 g total dietary fiber (TDF), 0.3 g soluble fiber (SF), & 0.4 g insoluble fiber (INSF), per 100 kcal; TF1: 3813 kcal/kg, 1.2 g TDF, 0.1 g SF, 1.0 g INSF per 100 kcal). 16 cats were assigned to group 2 & fed a control food (CF2): high grain formula without the fiber blend during a 3 week pre-feed, then switched to a test food (TF2): high grain formula with the fiber blend for 3 weeks (CF2: 3900 kcal/kg, 1.2 g TDF, 0.1 g SF, & 1.1 g INSF, per 100 kcal; TF2: 3950 kcal/kg, 1.8 g TDF, 0.5 g SF, 1.3 g INSF per 100 kcal). All foods were nutritionally complete & balanced dry foods & met 2019 AAFCO guidelines for adult cats. All cats were fed to maintain body weight. Stool samples were collected on pre-feed day 19±2& on day 19±2 of feeding each test food, & were scored on a 5 point scale (1= liquid stool to 5= firm stool), homogenized, & frozen at −70C within 4 hours of defecation. Untargeted metabolomics analysis was performed by a commercial lab. Fecal proximate & short chain fatty acid (SCFA) analyses were conducted using certified official compendial methods. All study protocols were reviewed & approved by the Institutional Animal Care & Use Committee, Hill's Pet Nutrition, Inc. A linear mixed model was used to analyze fecal moisture, pH, SCFAs, & metabolites. Results significant at p<0.05 are reported. Cats in both groups had increased levels of fecal metabolites derived from fiber, including phenolic compounds (eriodictyol, hesperidin, secoisolariciresinol diglucoside, narirutin & tangeritin), terpenoids (limonin, oleanolate, & pheophorbide A) & microbially-produced postbiotics (enterodiol, hesperetin, naringenin, ponciretin, & secoisolariciresinol) when fed TF1 & TF2 vs CF1 & CF2, respectively. Cats in group 1 had improved stool scores, decreased fecal moisture, decreased fecal pH, & increased fecal levels of the fiber derived saccharolytic metabolite arabinose when fed TF1 vs CF1. Cats in group 2 had decreased fecal levels of putrefactive metabolites, including branched SCFAs (isobutyric, 2-methylbutyric, & isovaleric acids) & polyamines (cadaverine, putrescine, & sperimidine) when fed TF2 vs CF2. Test foods containing this novel fiber blend improved stool parameters, increased fecal saccharolytic & fermentative metabolites, decreased putrefactive end products, & delivered antioxidant & anti-inflammatory plant-derived polyphenol postbiotics to the lower GI tract of adult cats.

Novel Dietary Fiber Blend Alters Metabolism of Gastrointestinal Microbiome to Improve Digestive Health and Produce Beneficial Postbiotics in Adult Dogs

The canine gastrointestinal (GI) microbiome is capable of fermenting a variety of plant fibers. Addition of dietary fibers from select plant sources may promote improvements in canine GI health. A novel fiber blend was prepared with pecan shells, flaxseed, beet pulp, citrus pulp & crushed cranberries.16 adult dogs were assigned to group 1 & fed a control food (CF1): hydrolyzed protein formula without the novel fiber blend during a 3 week pre-feed, then switched to the test food (TF1): hydrolyzed protein formula with the novel fiber blend for 3 weeks (CF1: 3770 kcal/kg, 0.3 g total dietary fiber (TDF), 0.1 g soluble fiber (SF), & 0.3 g insoluble fiber (INSF), per 100 kcal; TF1: 3646 kcal/kg, 2.7 g TDF, 0.4 g SF, 2.2 g INSF per 100 kcal). 16 dogs were assigned to group 2 & fed a control food (CF2): high grain formula without the novel fiber blend during a 3 week pre-feed, then switched to the test food (TF2): high grain formula with the novel fiber blend for 3 weeks (CF2: 3613 kcal/kg, 1.4 g TDF, 0.3 g SF, & 1.1 g INSF, per 100 kcal; TF2: 3580 kcal/kg, 2.0 g TDF, 0.1 g SF, 1.8 g INSF per 100 kcal). All foods were nutritionally complete & balanced dry foods & met 2019 AAFCO guidelines for adult dogs. All dogs were fed to maintain body weight. Stool samples were collected on pre-feed day 19±2& on day 19±2 of feeding each test food, & were scored on a 5 point scale (1= liquid stool to 5= firm stool), homogenized, & frozen at −70C within 1 hour of defecation. Untargeted metabolomics analysis was performed by a commercial lab. Fecal proximate & short chain fatty acid (SCFA) analyses were conducted using certified official compendial methods. All study protocols were reviewed & approved by the Institutional Animal Care & Use Committee, Hill's Pet Nutrition, Inc. A linear mixed model was used to analyze fecal moisture, pH, SCFAs, & metabolites. Results significant at p<0.05 are reported. Dogs in both groups had improved stool scores, decreased fecal pH, & increased levels of fecal metabolites derived from fiber, including saccharolytic products arabinose & ribulose/xylulose, phenolic compounds (apigenin, diosmetin, eriodictyol, hesperidin, narirutin & tangeritin), & microbially-produced postbiotics (4-hydroxycinnamate, enterodiol, hesperetin, naringenin, ponciretin, & secoisolariciresinol) when fed TF1 & TF2 vs CF1 & CF2, respectively. Dogs in group 1 had decreased fecal moisture & increased straight SCFAs (acetic acid, butyric acid, & propionic acid) when fed TF1 vs CF1. Dogs in group 2 had decreased fecal levels of putrefactive metabolites, including branched SCFAs (isobutyric, 2-methylbutyric, & isovaleric acids) & polyamines (putrescine, spermidine, & spermine) when fed TF2 vs CF2. Test foods containing this novel fiber blend improved stool parameters, increased fecal saccharolytic & fermentative metabolites, increased vital energy sources for colonocytes, decreased putrefactive end products, & increased antioxidant & anti-inflammatory plant-derived polyphenol postbiotics to the lower GI tract of adult dogs.

Twelve-month growth and accession of tolerance in infants with cow's milk protein allergy compared among those fed with breast milk or alternative formulae.

Cow's milk protein allergy (CMPA) is a common food allergy in children. The impact of various feeding regimens on growth in infants with CMPA is not sufficiently well understood. To investigate 12-month growth and accession of tolerance in infants with CMPA compared among those fed with breast milk or alternative formulae. This retrospective study included CMPA infants with treatment adherence for at least six months. Infants were categorized into the following feeding regimen groups: soy-based formula (SF), extensively hydrolyzed protein formula (EHF), commercial amino acid-based formula (cAAF), new amino acid-based formula (nAAF), chicken-based formula, and breast milk. Weight-for-age z-score (WAZ), length-for-age z-score (LAZ), and weight-for-length z-score (WLZ) were evaluated at diagnosis and at follow-ups. Clinical manifestations, other allergenic foods, and time to tolerance of CMP were assessed. One hundred and sixteen infants were enrolled. Infants consuming EHF had markedly improved WAZ. Infants with one symptom at diagnosis, those who had gastrointestinal symptom, and those with allergy to only CMP had more pronounced growth improvement. Compared to breast milk, SF and EHF were significantly associated with lower probability of tolerance to CMP (HR: 0.14, 95%CI: 0.03-0.62; and, HR: 0.21, 95%CI: 0.07-0.64, respectively). Those allergic to only CMP were more likely to develop tolerance to CMP than those allergic to CMP and other foods. Improvement in growth was significantly more pronounced in CMP-allergic infants fed with EHF. Accession of tolerance to CMP was associated with breast milk as the therapeutic diet.

The clinical effectiveness and safety of alprostadil combined with alpha lipoic acid in the treatment of diabetic peripheral neuropathy: A protocol for systematic review and meta-analysis.

Background:The pathogenesis of diabetic peripheral neuropathy is more complex and it is not yet clear, but studies have shown that microangiopathy and oxidative stress responses are closely related to their pathogenesis. At present, the treatment of improving microcirculation and antioxidant stress is mainly used in clinical. Alprostadil is a commonly used vasodilator, and alpha lipoic acid is an antioxidant, which can effectively reduce oxidative stress responses and delay the progression of diabetes mellitus and its complications. However, there is a lack of evidence-based medical evidence for alprostadil combined with alpha lipoic acid in the treatment of diabetic peripheral neuropathy, and this article aims to understand the clinical effectiveness and safety of alprostadil combined with alpha lipoic acid in the treatment of diabetic peripheral neuropath by a meta-analysis of published randomized controlled trials.Methods:In this study, we obtain the relevant literature by retrieving 8 electronic databases, including PubMed, EMBASE, Web of Science, the Cochrane Library, CBM, CNKI, VIP, and WanFang Database. Retrieving a randomized controlled study of alprostadil combined with alpha lipoic acid in the treatment of diabetic peripheral neuropath, while the language of the literature is restricted and it only includes Chinese and English literature. For the publication of literature, the time is from the beginning of the database to August 31, 2020. In the English database, using the retrieval method of subject word combined free word. The two researchers read the titles and abstracts of all the literature independently based on the inclusion and exclusion criteria. If it cannot be determined whether the literature is included by reading the title and abstract, then download and read the full text of the literature. If there is a dispute between the two researchers about the literature, so it should discuss the dispute with the third researcher in order to reach a conclusion. Using the bias risk assessment tool of randomized controlled trials in Cochrane systematic review to evaluate the bias risk of the included literature; Using RevMan 5.3 software to conduct statistical analysis; Using funnel plot analysis to analyze the situation of literature publication bias.Results:This study will provide a high-quality evidence on the effects of hydrolyzed protein formula milk on gastrointestinal diseases and physical development of premature infants.Conclusion:This study will draw reliable evidence-based medical evidence for alprostadil combined with Alpha lipoic acid in the treatment of diabetic peripheral neuropathy, thus providing help for the clinical treatment of diabetic peripheral neuropathy.Registration number:Open Science Framework (OSF), registration number: DOI 10.17605/OSF.IO/7S46G.

The effect of preventive use of hydrolyzed protein formula milk on gastrointestinal diseases and physical development of premature infants: A protocol for systematic review and meta-analysis.

Background:Because of the controversy in clinical nutritional support therapy of hydrolyzed protein formula milk and standard preterm infant formula (SPIF) in premature infants. In this study, the effectiveness and safety of preventive use of hydrolyzed protein formula milk in reducing gastrointestinal diseases and promoting physical development of premature infants are scientifically evaluated by systematic evaluation. To help find the suitable nutritional support for premature infants.Methods:To search the database of Chinese and English by computer: SinoMed, CNKI, WanFang Data, VIP, PubMed, EMbase and The Cochrane Library, and to collect randomized controlled trials on the application of hydrolyzed protein formula milk in nutritional support treatment of premature infants compared with SPIF. The retrieval time limit is from the establishment of each database to September 1, 2020. Two authors independently completed the paper search, and sorting out the main outcome indicator and secondary outcome indicator in the selected literature, and the data are statistically analyzed by Review Manager software (RevManV.5.3.0) and STATA 13.0.Results:This study will provide a high-quality evidence on the effects of hydrolyzed protein formula milk on gastrointestinal diseases and physical development of premature infants.Conclusion:At present, the clinicians are controversial about the safety and effectiveness of hydrolyzed protein formula milk and SPIF in the nutritional support therapy of premature infants. This study will compare the effectiveness and safety of these 2 nutritional support methods, and make a comprehensive analysis of the influence of hydrolyzed protein formula milk on gastrointestinal diseases and physical development of premature infants, and finally give a positive conclusion.OSF registration number:DOI 10.17605/OSF.IO/UQD92

Stool microbiome, pH and short/branched chain fatty acids in infants receiving extensively hydrolyzed formula, amino acid formula, or human milk through two months of age

BackgroundEarly infant feeding with intact or extensively hydrolyzed (EH) proteins or free amino acids (AA) may differentially affect intestinal microbiota composition and immune reactivity. This multicenter, double-blind, controlled, parallel-group, pilot study compared stool microbiota from Baseline (1–7 days of age) up to 60 days of age in healthy term infants who received mother’s own milk (assigned to human milk [HM] reference group) (n = 25) or were randomized to receive one of two infant formulas: AA-based (AAF; n = 25) or EH cow’s milk protein (EHF; n = 28). Stool samples were collected (Baseline, Day 30, Day 60) and 16S rRNA genes were sequenced. Alpha (Shannon, Simpson, Chao1) and beta diversity (Bray Curtis) were analyzed. Relative taxonomic enrichment and fold changes were analyzed (Wilcoxon, DESEq2). Short/branched chain fatty acids (S/BCFA) were quantified by gas chromatography. Mean S/BCFA and pH were analyzed (repeated measures ANOVA).ResultsAt baseline, alpha diversity measures were similar among all groups; however, both study formula groups were significantly higher versus the HM group by Day 60. Significant group differences in beta diversity at Day 60 were also detected, and study formula groups were compositionally more similar compared to HM. The relative abundance of Bifidobacterium increased over time and was significantly enriched at Day 60 in the HM group. In contrast, a significant increase in members of Firmicutes for study formula groups were detected at Day 60 along with butyrate-producing species in the EHF group. Stool pH was significantly higher in the AAF group at Days 30 and 60. Butyrate increased significantly from Baseline to Day 60 in the EHF group and was significantly higher in study formula groups vs HM at Day 60. Propionate was also significantly higher for EHF and AAF at Day 30 and AAF at Day 60 vs HM. Total and individual BCFA were higher for AAF and EHF groups vs HM through Day 60.ConclusionsDistinct patterns of early neonatal microbiome, pH, and microbial metabolites were demonstrated for infants receiving mother’s own milk compared to AA-based or extensively hydrolyzed protein formula. Providing different sources of dietary protein early in life may influence gut microbiota and metabolites.Trial registrationClinicalTrials.gov Identifier: NCT02500563. Registered July 28, 2015.

A cross sectional survey in paediatricians pertaining to management of functional gastrointestinal disorders in infants: Indian perspectives

Background: Functional gastrointestinal disorders (FGIDs) in infants and toddlers possess extensive burden to the parents and healthcare professionals. Guidelines addressing the practices in diagnosis and management of FGIDs in infants in Indian subcontinent is unavailable. Hence this study assessed current knowledge, attitude and practice of pediatricians in diagnosis and treatment of FGIDs.Methods: A cross-sectional survey based on a structured questionnaire assessed pediatrician’s knowledge about prevalence and profile of most common GI disorders in pediatric age groups (birth to 12 months), association of FGIDs with different feeding practices, impact of FGID on quality of life, various management options and physician preferred method of treatment.Results: Colic was rated as the most common GI disorder, followed by gassiness/fussiness, regurgitation and constipation. About 59% pediatricians come across FGIDs more in formula-fed infants compared to breastfed infants (4.2%) and 93.9% pediatricians affirm that FGIDs affect quality of life. Approximately 91% pediatricians believed reassurance and education was the best management option, which was also reported as the preferred mode of management by about 89% pediatricians, whereas pharmacological therapies were the least preferred (1.6%). For breastfed infants suffering with regurgitation, colic or constipation, majority pediatricians opted for switching to 100% whey partially hydrolysed protein formula; sequentially followed by use of pre/probiotics and switch to extensively hydrolyzed protein formula.Conclusions: Parental education and reassurance offer an ideal mode of management of FGIDs. Partially hydrolysed protein formula may be considered one of the best management options irrespective of the FGID condition in infants who are breastfeed.

The Role and Place of Partially Hydrolysed Protein Infant Formulas in the Nutrition of Full-term Children: Digestive Comfort and Allergy Prevention

The continued increase in the number of allergic diseases and the high prevalence of digestive disturbances in infants explain the interest of pediatricians, allergists and gastroenterologists in the development and improvement of nutritional methods for the prevention and correction of these pathologies. This article discusses current ideas on the role of partially hydrolysed protein formulas in infants’ nutrition for recovery of most common functional gastrointestinal disorders, allergy primary prevention. Also, the article discusses formulas place in sequential nutrition therapy of food allergy. Descriptions of cow milk proteins molecular characteristics and its allergens properties are presented. Features of creation and production of partially hydrolysed protein formulas are described as well.

Hydrolyzed Protein Formula for Allergy Prevention in Preterm Infants: Follow-Up Analysis of a Randomized, Triple-Blind, Placebo-Controlled Study.

Background: Allergic diseases are a major public health burden worldwide. Evidence suggests that early nutrition might play a key role in the future development of allergies and the use of hydrolyzed protein formulas have been proposed to prevent allergic disease, mainly in term infants with risk factors.Aim: To evaluate the preventive effect of a hydrolyzed protein formula vs. an intact protein formula on allergy development in preterm infants with or without risk factors.Methods: We performed a 3-year follow-up study of a previous triple-blind, placebo-controlled randomized trial. Evidence of atopic dermatitis, asthma and IgE-mediated food allergies were evaluated according to a validated parental questionnaire (Comprehensive Early Childhood Allergy Questionnaire). Food sensitization was also investigated by skin prick test at 3 years of chronological age.Results: Of the 30 subjects in the intact protein formula group and 30 in the extensively hydrolyzed formula group, respectively 18 and 16 completed the 3-year follow-up and entered the final analysis. No group differences in the incidence of atopic dermatitis, asthma, IgE-mediated food allergies, and food sensitization were found.Conclusion: Despite the small number of cases, extensively hydrolyzed protein formula seems to be ineffective in allergic diseases prevention in preterm neonates. Further adequately powered, randomized controlled trials evaluating hydrolyzed protein formula administration to prevent allergic diseases in preterm neonates are needed.

Assessing Early Indicators of Tolerance and Stool Microbiome in Infants Receiving Formula with Added Lactobacillus rhamnosus GG (LGG)

Abstract Objectives To evaluate stool microbiome and calprotectin in infants receiving partially hydrolyzed protein formula with or without Lactobacillus rhamnosus GG (LGG). Methods In this single-center, double-blind, controlled, parallel, prospective study, infants (14-28 days of age) experiencing crying/fussing often associated with infantile colic were randomized to receive one of two formulas over a 21-day feeding period: marketed partially hydrolyzed (PH) cow's milk-based infant formula (PH: n, 35) or a similar formula with added LGG (PH-LGG: n, 36). Stool samples were collected at Baseline and Study End (Days 19–21). Stool calprotectin (μg/g) was determined by immunoassay and analyzed (Kruskal-Wallis). LGG colonization was determined by qPCR analysis.16S rRNA gene sequencing was performed (Illumina MiSeq) and QIIME operational taxonomic units (OTUs) were assigned (Greengenes database). Alpha and beta diversity were analyzed by study group and time point. Results A significantly higher abundance of LGG was demonstrated at Study End vs Baseline for the PH-LGG (P &amp;lt; 0.001) but not PH group (P = 0.89). Alpha diversity (Shannon) was significantly higher at Study End vs Baseline in the PH group (P = 0.014). By Study End, members of Phylum Firmicutes were significantly higher (P = 0.002) and Family Enterococcaceae were significantly lower (P = 0.02) in the PH-LGG group. No group differences in stool calprotectin (median) were detected at Baseline (PH: 12.4, n = 26; PH-LGG: 13.9, n = 30) or Study End (PH: 12.4, n = 30; PH-LGG: 12.9, n = 30). Conclusions In infants receiving a partially hydrolyzed protein formula with added LGG over a 21-day feeding period, LGG was established in the stool microbiome. Associated potentially beneficial bacterial taxa were also increased. Funding Sources Mead Johnson Nutrition.

Сравнительные вкусовые характеристики высокогидролизованных смесей – результаты анкетирования врачей

Objective. To compare the palatability of six extensively hydrolyzed formulas used in the Russian Federation for diet therapy in case of cow’s milk protein allergy. Materials and methods. А direct taste-testing of six specialized formulas with a subsequent questionnaire survey was performed among 336 paediatricians and paediatric allergologists. Results. A whey protein hydrolysate formula containing galacto- and fructooligosaccharides with lactose reduced contents scored higher (8.0 ± 1.8 out of 10, p &lt; 0.01). On the whole, whey protein hydrolysates are more palatable compared to casein hydrolysates (5.7 ± 1.7 vs 3.5 ± 2.1, p &lt; 0.01). Conclusion. Extensively hydrolyzed formulas differ significantly in their taste attributes. Whey protein hydrolysates containing prebiotic oligosaccharides and lactose have the best palatability among other extensively hydrolyzed formulas. Key words: cow’s milk protein allergy, extensively hydrolyzed formulas, hydrolysate taste, peptide size

Protein hydrolysate versus standard formula for preterm infants.

When human milk is not available for feeding preterm infants, protein hydrolysate, rather than standard cow's milk formulas (with intact proteins), is often used because it is perceived as being tolerated better and less likely to lead to complications. However, protein hydrolysate formulas are more expensive than standard formulas, and concern exists that their use in practice is not supported by high-quality evidence. To assess the effects of feeding preterm infants hydrolysed formula (vs standard cow's milk formula) on risk of feed intolerance, necrotising enterocolitis, and other morbidity and mortality. We used the standard Cochrane Neonatal search strategy including electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 1), in the Cochrane Library; Ovid MEDLINE (1966 to 28 January 2019); Ovid Embase (1980 to 28 January 2019); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (28 January 2019), as well as conference proceedings and previous reviews. Randomised and quasi-randomised controlled trials that compared feeding preterm infants protein hydrolysate versus standard (non-hydrolysed) cow's milk formula. Two review authors assessed trial eligibility and risk of bias and extracted data independently. We analysed treatment effects as described in the individual trials and reported risk ratios and risk differences for dichotomous data, and mean differences for continuous data, with respective 95% confidence intervals (CIs). We used a fixed-effect model in meta-analyses and explored potential causes of heterogeneity in sensitivity analyses. We assessed quality of evidence at the outcome level using the GRADE approach. We identified 11 trials for inclusion in the review. All trials were small (total participants 665) and had various methodological limitations including uncertainty about methods to ensure allocation concealment and blinding. Most participants were clinically stable preterm infants of less than about 34 weeks' gestational age or with birth weight less than about 1750 g. Fewer participants were extremely preterm, extremely low birth weight, or growth restricted. Most trials found no effects on feed intolerance, assessed variously as mean pre-feed gastric residual volume, incidence of abdominal distension or other gastrointestinal signs of concern, or time taken to achieve full enteral feeds (meta-analysis was limited because studies used different measures). Meta-analysis showed no effect on the risk of necrotising enterocolitis (typical risk ratio 1.10, 95% CI 0.36 to 3.34; risk difference 0.00, 95% CI -0.03 to 0.04; 5 trials, 385 infants) (low-certainty evidence; downgraded for imprecision and design weaknesses). The identified trials provide only low-certainty evidence about the effects of feeding preterm infants protein hydrolysate versus standard formula. Existing data do not support conclusions that feeding protein hydrolysate affects the risk of feed intolerance or necrotising enterocolitis. Additional large, pragmatic trials are needed to provide more reliable and precise estimates of effectiveness and cost-effectiveness.

Stool pH and Short/Branched Chain Fatty Acids in Infants Receiving Extensively Hydrolyzed Formula, Amino Acid Formula, or Human Milk Through Two Months of Age (P11-076-19)

ObjectivesInfant feeding influences early development of the gut microbiome, colonization pattern, and community structure. Metabolites, including short- and branched-chain fatty acids (S/BCFA) (e.g., butyrate, propionate), produced by colonic bacteria serve as signaling molecules, influence immunity, and reduce luminal pH in the gastrointestinal environment. The objective of this study was to evaluate stool S/BCFA and pH in infants fed with different sources of dietary protein. MethodsIn this multicenter, double-blind, controlled, parallel-group, pilot study, healthy term infants were randomized to receive one of two infant formulas (IF): amino-acid based (AAF; n = 25) or extensively hydrolyzed cow’s milk protein (EHF; n = 28) from Baseline (1-7 days of age) up to 60 days of age. A human milk reference group (HM; n = 25) received mother’s own milk over the same period. Diethyl ether extractions of S/BCFA from stool samples (Baseline, Day 30, and Day 60) were quantified by gas chromatography (Clarus 580; PerkinElmer) using a fused silica capillary column (Nukol 30m × 0.25mm id × 0.25μm film). Mean stool S/BCFA (μmol/g) and pH were analyzed by repeated measures analysis of variance (ANOVA). ResultsComplete stool data (all study time points) were available for 49 participants. Stool pH (∼6) was similar among groups at Baseline with no significant changes for HM and EHF groups through Day 60. The AAF group was significantly higher at Days 30 and 60 (Figure 1). Total SCFA were similar for all groups through Day 60. Butyrate increased significantly from Baseline to Day 60 in the EHF group (P = 0.026) and was significantly higher vs HM at Days 30 and 60 (P = 0.0009 and 0.0004 respectively). Butyrate was significantly higher for AAF vs HM at Day 60 only (P = 0.038). Propionate was significantly higher for EHF and AAF at Day 30 (P = 0.0009 and < 0.0001 respectively) and AAF only at Day 60 (P = 0.005) vs HM. Total and individual BCFA increased for AAF and EHF groups vs HM through Day 60. ConclusionsDistinct patterns of pH and microbial metabolites were demonstrated for infants receiving mother’s own milk compared to amino acid-based or extensively hydrolyzed protein formula. Providing different sources of dietary protein early in life may influence gut microbiota and metabolites. Funding SourcesMead Johnson Pediatric Nutrition Institute. Supporting Tables, Images and/or Graphs▪