Research

14 pages, 890 KiB

Open AccessArticle

Evaluation of Safety and Beneficial Health Effects of the Human-Milk Strain Bifidobacterium breve DSM32583: An Infant Pilot Trial

by Claudio Alba, Marta Carrera, Guillermo Álvarez-Calatayud, Rebeca Arroyo, Leónides Fernández and Juan M. Rodríguez

Nutrients 2024, 16(8), 1134; https://doi.org/10.3390/nu16081134 - 11 Apr 2024

Viewed by 310

Abstract

Human milk promotes the growth of bifidobacteria in the infant gut. Adding bifidobacterial species to infant formula may contribute to increasing their presence in the gut of formula-fed infants. Therefore, the safety and anti-infectious effects of Bifidobacterium breve DSM32583, a breast milk isolate, [...] Read more.

Human milk promotes the growth of bifidobacteria in the infant gut. Adding bifidobacterial species to infant formula may contribute to increasing their presence in the gut of formula-fed infants. Therefore, the safety and anti-infectious effects of Bifidobacterium breve DSM32583, a breast milk isolate, were assessed in a pilot trial involving 3-month-old infants. The infants were randomly assigned to either the probiotic (PG) or the control (CG) groups. All the infants consumed the same formula, although it was supplemented with the strain (1 × 10⁷ cfu/g of formula) in the PG. Overall, 160 infants (80 per group) finished the intervention. Infants in CG gained more weight compared to PG (p < 0.05), but the weights for age Z-scores at 6 months were within the normal distribution for this age group. The rates of infections affecting the gastrointestinal and respiratory tracts and antibiotic therapy were significantly lower in the PG. The bifidobacterial population and the level of short-chain fatty acids were higher (p < 0.05) in the fecal samples of PG infants. No adverse events related to formula consumption were observed. In conclusion, the administration of an infant formula with B. breve DSM32583 was safe and exerted potential beneficial effects on gut health. Full article

(This article belongs to the Special Issue Effects of Breast Milk and Formula on Infant Intestinal Health and the Infant Gut Microbiome)

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15 pages, 3103 KiB

Open AccessArticle

Untargeted Metabolomic Analysis of Lactation-Stage-Matched Human and Bovine Milk Samples at 2 Weeks Postnatal

by Dominick J. Lemas, Xinsong Du, Bethany Dado-Senn, Ke Xu, Amanda Dobrowolski, Marina Magalhães, Juan J. Aristizabal-Henao, Bridget E. Young, Magda Francois, Lindsay A. Thompson, Leslie A. Parker, Josef Neu, Jimena Laporta, Biswapriya B. Misra, Ismael Wane, Samih Samaan and Timothy J. Garrett

Nutrients 2023, 15(17), 3768; https://doi.org/10.3390/nu15173768 - 29 Aug 2023

Cited by 1 | Viewed by 1617

Abstract

Epidemiological data demonstrate that bovine whole milk is often substituted for human milk during the first 12 months of life and may be associated with adverse infant outcomes. The objective of this study is to interrogate the human and bovine milk metabolome at [...] Read more.

Epidemiological data demonstrate that bovine whole milk is often substituted for human milk during the first 12 months of life and may be associated with adverse infant outcomes. The objective of this study is to interrogate the human and bovine milk metabolome at 2 weeks of life to identify unique metabolites that may impact infant health outcomes. Human milk (n = 10) was collected at 2 weeks postpartum from normal-weight mothers (pre-pregnant BMI < 25 kg/m²) that vaginally delivered term infants and were exclusively breastfeeding their infant for at least 2 months. Similarly, bovine milk (n = 10) was collected 2 weeks postpartum from normal-weight primiparous Holstein dairy cows. Untargeted data were acquired on all milk samples using high-resolution liquid chromatography–high-resolution tandem mass spectrometry (HR LC-MS/MS). MS data pre-processing from feature calling to metabolite annotation was performed using MS-DIAL and MS-FLO. Our results revealed that more than 80% of the milk metabolome is shared between human and bovine milk samples during early lactation. Unbiased analysis of identified metabolites revealed that nearly 80% of milk metabolites may contribute to microbial metabolism and microbe–host interactions. Collectively, these results highlight untargeted metabolomics as a potential strategy to identify unique and shared metabolites in bovine and human milk that may relate to and impact infant health outcomes. Full article

(This article belongs to the Special Issue Effects of Breast Milk and Formula on Infant Intestinal Health and the Infant Gut Microbiome)

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19 pages, 5702 KiB

Open AccessArticle

Probiotics and Human Milk Differentially Influence the Gut Microbiome and NEC Incidence in Preterm Pigs

by Valeria Melendez Hebib, Diana H. Taft, Barbara Stoll, Jinxin Liu, Lee Call, Gregory Guthrie, Nick Jensen, Amy B. Hair, David A. Mills and Douglas G. Burrin

Nutrients 2023, 15(11), 2585; https://doi.org/10.3390/nu15112585 - 31 May 2023

Cited by 3 | Viewed by 2111

Abstract

Necrotizing enterocolitis (NEC) is the leading cause of death caused by gastrointestinal disease in preterm infants. Major risk factors include prematurity, formula feeding, and gut microbial colonization. Microbes have been linked to NEC, yet there is no evidence of causal species, and select [...] Read more.

Necrotizing enterocolitis (NEC) is the leading cause of death caused by gastrointestinal disease in preterm infants. Major risk factors include prematurity, formula feeding, and gut microbial colonization. Microbes have been linked to NEC, yet there is no evidence of causal species, and select probiotics have been shown to reduce NEC incidence in infants. In this study, we evaluated the effect of the probiotic Bifidobacterium longum subsp. infantis (BL. infantis), alone and in combination with a human milk oligosaccharide (HMO)—sialylactose (3′SL)—on the microbiome, and the incidence of NEC in preterm piglets fed an infant formula diet. We studied 50 preterm piglets randomized between 5 treatments: (1) Preterm infant formula, (2) Donor human milk (DHM), (3) Infant formula + 3′SL, (4) Infant formula + BL. infantis, and (5) Infant formula and BL. infantis + 3′SL. NEC incidence and severity were assessed through the evaluation of tissue from all the segments of the GI tract. The gut microbiota composition was assessed both daily and terminally through 16S and whole-genome sequencing (WGS) of rectal stool samples and intestinal contents. Dietary BL. infantis and 3′SL supplementation had no effect, yet DHM significantly reduced the incidence of NEC. The abundance of BL. infantis in the gut contents negatively correlated with disease severity. Clostridium sensu stricto 1 and Clostridium perfringens were significantly more abundant in NEC and positively correlated with disease severity. Our results suggest that pre- and probiotics are not sufficient for protection from NEC in an exclusively formula-based diet. The results highlight the differences in microbial species positively associated with both diet and NEC incidence. Full article

(This article belongs to the Special Issue Effects of Breast Milk and Formula on Infant Intestinal Health and the Infant Gut Microbiome)

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12 pages, 745 KiB

Open AccessArticle

Limosilactobacillus reuteri DSM 17938-Containing Infant Formulas and the Associations with Gastrointestinal Tolerance: A Cross-Sectional Observational Study

by Happy Tummy Consortium, Luca Lavalle, Nicolas Sauvageot, Colin Ivano Cercamondi, Ivana Jankovic, Delphine Egli and Yvan Vandenplas

Nutrients 2023, 15(3), 530; https://doi.org/10.3390/nu15030530 - 19 Jan 2023

Cited by 2 | Viewed by 2532

Abstract

Limosilactobacillus (L.; previously Lactobacillus) reuteri has been shown to influence gastrointestinal (GI) tolerance. This study was a secondary analysis of GI tolerance data from a multi-country, cross-sectional, observational study in healthy infants using the validated Infant Gastrointestinal Symptom Questionnaire (IGSQ) [...] Read more.

Limosilactobacillus (L.; previously Lactobacillus) reuteri has been shown to influence gastrointestinal (GI) tolerance. This study was a secondary analysis of GI tolerance data from a multi-country, cross-sectional, observational study in healthy infants using the validated Infant Gastrointestinal Symptom Questionnaire (IGSQ) and a gut comfort questionnaire. Breastfed infants (BFI; n = 760) were compared to formula-fed infants receiving either L. reuteri-containing formula (FFI + LR; n = 470) or standard formula without any probiotic or prebiotic (FFI-Std; n = 501). The IGSQ composite scores (adjusted mean ± SE) in FFI + LR (22.17 ± 0.39) was significantly lower than in FFI-Std (23.41 ± 0.37) and similar to BFI (22.34 ± 0.30;), indicating better GI tolerance in FFI + LR than in FFI-Std. Compared with FFI-Std, FFI + LR had lower reports of difficulty in passing stools (11% vs. 22%; adjusted-odds ratio (OR) (95%CI) = 0.46 (0.31–0.68)), fewer hard stools (mean difference = −0.12 (−0.21, −0.02)) and less physician-confirmed colic (OR = 0.61 (0.45–0.82)), and similar to BFI. Parent-reported crying time (mean difference = −0.15 (−0.28, −0.01)), frequency of spitting-up/vomiting (mean difference = −0.18 (−0.34, −0.03)), volume of spit-up (mean difference = −0.20 (−0.32, −0.08)) and fussiness due to spitting-up/vomiting (mean difference = −0.17 (−0.29, −0.05)) were lower in FFI + LR versus FFI-Std and similar to BFI. In this study, L. reuteri-containing formula was associated with improved digestive tolerance and behavioral patterns. Full article

(This article belongs to the Special Issue Effects of Breast Milk and Formula on Infant Intestinal Health and the Infant Gut Microbiome)

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13 pages, 1168 KiB

Open AccessArticle

Gut Microbiome Composition and Metabolic Capacity Differ by FUT2 Secretor Status in Exclusively Breastfed Infants

by Alexander W. Thorman, Grace Adkins, Shannon C. Conrey, Allison R. Burrell, Ying Yu, Brendon White, Rachel Burke, David Haslam, Daniel C. Payne, Mary A. Staat, Ardythe L. Morrow and David S. Newburg

Nutrients 2023, 15(2), 471; https://doi.org/10.3390/nu15020471 - 16 Jan 2023

Cited by 5 | Viewed by 2917

Abstract

A major polymorphism in the fucosyltransferase2 (FUT2) gene influences risk of multiple gut diseases, but its impact on the microbiome of breastfed infants was unknown. In individuals with an active FUT2 enzyme (“secretors”), the intestinal mucosa is abundantly fucosylated, providing mutualist [...] Read more.

A major polymorphism in the fucosyltransferase2 (FUT2) gene influences risk of multiple gut diseases, but its impact on the microbiome of breastfed infants was unknown. In individuals with an active FUT2 enzyme (“secretors”), the intestinal mucosa is abundantly fucosylated, providing mutualist bacteria with a rich endogenous source of fucose. Non-secretors comprise approximately one-fifth of the population, and they lack the ability to create this enzyme. Similarly, maternal secretor status influences the abundance of a breastfeeding mother’s fucosylated milk oligosaccharides. We compared the impact of maternal secretor status, measured by FUT2 genotype, and infant secretor status, measured by FUT2 genotype and phenotype, on early infant fecal microbiome samples collected from 2-month-old exclusively breastfed infants (n = 59). Infant secretor status (19% non-secretor, 25% low-secretor, and 56% full-secretor) was more strongly associated with the infant microbiome than it was with the maternal FUT2 genotype. Alpha diversity was greater in the full-secretors than in the low- or non-secretor infants (p = 0.049). Three distinct microbial enterotypes corresponded to infant secretor phenotype (p = 0.022) and to the dominance of Bifidobacterium breve, B. longum, or neither (p < 0.001). Infant secretor status was also associated with microbial metabolic capacity, specifically, bioenergetics pathways. We concluded that in exclusively breastfed infants, infant—but not maternal—secretor status is associated with infant microbial colonization and metabolic capacity. Full article

(This article belongs to the Special Issue Effects of Breast Milk and Formula on Infant Intestinal Health and the Infant Gut Microbiome)

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10 pages, 1350 KiB

Open AccessArticle

Early Enteral Feeding of the Preterm Infant—Delay until Own Mother’s Breastmilk Becomes Available? (Israel, 2012–2017)

by Noa Ofek Shlomai, Yonatan Shneor Patt, Yaara Wazana, Tomer Ziv-Baran, Tzipora Strauss and Iris Morag

Nutrients 2022, 14(23), 5035; https://doi.org/10.3390/nu14235035 - 26 Nov 2022

Cited by 1 | Viewed by 1886

Abstract

Aim: To consider the question of whether to initiate trophic feeds with formula in the absence of own mother’s breastmilk or to wait for breastmilk to be available. Methods: A retrospective study of infants born prior to 32 weeks of gestation during the [...] Read more.

Aim: To consider the question of whether to initiate trophic feeds with formula in the absence of own mother’s breastmilk or to wait for breastmilk to be available. Methods: A retrospective study of infants born prior to 32 weeks of gestation during the period 2012–2017 at a single tertiary center in Tel Aviv, Israel. Three TF groups were defined: exclusive breastmilk, mixed, and exclusive formula. Univariate and multivariate analyses were conducted. Logistic regression was used, and adjusted odds ratio and 95% interval were reported. Results: Univariate analysis demonstrated that infants in the exclusive breastmilk group were born earlier, had lower birth weights and lower Apgar scores, were given lower volumes of TF, and were more likely to have a longer hospital stay. Poor composite outcome was more common among the exclusive breastmilk group. Multivariate regression analysis revealed no differences in incidence of early neonatal morbidities between the groups, except for longer duration of parenteral nutrition in the exclusive breastmilk group. Conclusion: In our cohort, exclusive formula TF was not associated with increased risk of any of the studied morbidities. Clinicians should consider this finding in deciding between early TF or fasting while waiting for own mother’s breastmilk. Full article

(This article belongs to the Special Issue Effects of Breast Milk and Formula on Infant Intestinal Health and the Infant Gut Microbiome)

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Review

Jump to: Research, Other

12 pages, 322 KiB

Open AccessReview

Antimicrobial Resistance Genes (ARGs), the Gut Microbiome, and Infant Nutrition

by Rufus J. Theophilus and Diana Hazard Taft

Nutrients 2023, 15(14), 3177; https://doi.org/10.3390/nu15143177 - 18 Jul 2023

Cited by 3 | Viewed by 2642

Abstract

The spread of antimicrobial resistance genes (ARGs) is a major public health crisis, with the ongoing spread of ARGs leading to reduced efficacy of antibiotic treatments. The gut microbiome is a key reservoir for ARGs, and because diet shapes the gut microbiome, diet [...] Read more.

The spread of antimicrobial resistance genes (ARGs) is a major public health crisis, with the ongoing spread of ARGs leading to reduced efficacy of antibiotic treatments. The gut microbiome is a key reservoir for ARGs, and because diet shapes the gut microbiome, diet also has the potential to shape the resistome. This diet–gut microbiome–resistome relationship may also be important in infants and young children. This narrative review examines what is known about the interaction between the infant gut microbiome, the infant resistome, and infant nutrition, including exploring the potential of diet to mitigate infant ARG carriage. While more research is needed, diet has the potential to reduce infant and toddler carriage of ARGs, an important goal as part of maintaining the efficacy of available antibiotics and preserving infant and toddler health. Full article

(This article belongs to the Special Issue Effects of Breast Milk and Formula on Infant Intestinal Health and the Infant Gut Microbiome)

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21 pages, 1015 KiB

Open AccessReview

Limosilactobacillus fermentum CECT5716: Clinical Potential of a Probiotic Strain Isolated from Human Milk

by Metehan Ozen, Hugues Piloquet and Monika Schaubeck

Nutrients 2023, 15(9), 2207; https://doi.org/10.3390/nu15092207 - 06 May 2023

Cited by 4 | Viewed by 3336

Abstract

Breastfeeding provides the ideal nutrition for infants. Human milk contains a plethora of functional ingredients which foster the development of the immune system. The human milk microbiota predominantly contributes to this protective effect. This is mediated by various mechanisms, such as an antimicrobial [...] Read more.

Breastfeeding provides the ideal nutrition for infants. Human milk contains a plethora of functional ingredients which foster the development of the immune system. The human milk microbiota predominantly contributes to this protective effect. This is mediated by various mechanisms, such as an antimicrobial effect, pathogen exclusion and barrier integrity, beneficial effects on the gastrointestinal microbiota, vitamin synthesis, immunity enhancement, secreted probiotic factors, and postbiotic mechanisms. Therefore, human milk is a good source for isolating probiotics for infants who cannot be exclusively breastfed. One such probiotic which was isolated from human milk is Limosilactobacillus fermentum CECT5716. In this review, we give an overview of available interventional studies using Limosilactobacillus fermentum CECT5716 and summarise preclinical trials in several animal models of different pathologies, which have given first insights into its mechanisms of action. We present several randomised clinical studies, which have been conducted to investigate the clinical efficacy of the Limosilactobacillus fermentum CECT5716 strain in supporting the host’s health. Full article

(This article belongs to the Special Issue Effects of Breast Milk and Formula on Infant Intestinal Health and the Infant Gut Microbiome)

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16 pages, 831 KiB

Open AccessReview

Human Milk Microbiome and Microbiome-Related Products: Potential Modulators of Infant Growth

by Jie Ma, Debra J. Palmer, Donna Geddes, Ching Tat Lai and Lisa Stinson

Nutrients 2022, 14(23), 5148; https://doi.org/10.3390/nu14235148 - 03 Dec 2022

Cited by 8 | Viewed by 3550

Abstract

Infant growth trajectory may influence later-life obesity. Human milk provides a wide range of nutritional and bioactive components that are vital for infant growth. Compared to formula-fed infants, breastfed infants are less likely to develop later-onset obesity, highlighting the potential role of bioactive [...] Read more.

Infant growth trajectory may influence later-life obesity. Human milk provides a wide range of nutritional and bioactive components that are vital for infant growth. Compared to formula-fed infants, breastfed infants are less likely to develop later-onset obesity, highlighting the potential role of bioactive components present in human milk. Components of particular interest are the human milk microbiota, human milk oligosaccharides (HMOs), short-chain fatty acids (SCFAs), and antimicrobial proteins, each of which influence the infant gut microbiome, which in turn has been associated with infant body composition. SCFAs and antimicrobial proteins from human milk may also systemically influence infant metabolism. Although inconsistent, multiple studies have reported associations between HMOs and infant growth, while studies on other bioactive components in relation to infant growth are sparse. Moreover, these microbiome-related components may interact with each other within the mammary gland. Here, we review the evidence around the impact of human milk microbes, HMOs, SCFAs, and antimicrobial proteins on infant growth. Breastfeeding is a unique window of opportunity to promote optimal infant growth, with aberrant growth trajectories potentially creating short- and long-term public health burdens. Therefore, it is important to understand how bioactive components of human milk influence infant growth. Full article

(This article belongs to the Special Issue Effects of Breast Milk and Formula on Infant Intestinal Health and the Infant Gut Microbiome)

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25 pages, 915 KiB

Open AccessReview

Exploring the Potential of Human Milk and Formula Milk on Infants’ Gut and Health

by Hui-Yuan Chong, Loh Teng-Hern Tan, Jodi Woan-Fei Law, Kar-Wai Hong, Vanassa Ratnasingam, Nurul-Syakima Ab Mutalib, Learn-Han Lee and Vengadesh Letchumanan

Nutrients 2022, 14(17), 3554; https://doi.org/10.3390/nu14173554 - 29 Aug 2022

Cited by 23 | Viewed by 7366

Abstract

Early-life gut microbiota plays a role in determining the health and risk of developing diseases in later life. Various perinatal factors have been shown to contribute to the development and establishment of infant gut microbiota. One of the important factors influencing the infant [...] Read more.

Early-life gut microbiota plays a role in determining the health and risk of developing diseases in later life. Various perinatal factors have been shown to contribute to the development and establishment of infant gut microbiota. One of the important factors influencing the infant gut microbial colonization and composition is the mode of infant feeding. While infant formula milk has been designed to resemble human milk as much as possible, the gut microbiome of infants who receive formula milk differs from that of infants who are fed human milk. A diverse microbial population in human milk and the microbes seed the infant gut microbiome. Human milk contains nutritional components that promote infant growth and bioactive components, such as human milk oligosaccharides, lactoferrin, and immunoglobulins, which contribute to immunological development. In an attempt to encourage the formation of a healthy gut microbiome comparable to that of a breastfed infant, manufacturers often supplement infant formula with prebiotics or probiotics, which are known to have a bifidogenic effect and can modulate the immune system. This review aims to elucidate the roles of human milk and formula milk on infants’ gut and health. Full article

(This article belongs to the Special Issue Effects of Breast Milk and Formula on Infant Intestinal Health and the Infant Gut Microbiome)

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Other

Jump to: Research, Review

9 pages, 848 KiB

Open AccessBrief Report

Iron and DHA in Infant Formula Purchased in the US Fails to Meet European Nutrition Requirements

by Alexander Strzalkowski, Grace Black and Bridget E. Young

Nutrients 2023, 15(8), 1812; https://doi.org/10.3390/nu15081812 - 08 Apr 2023

Cited by 1 | Viewed by 1565

Abstract

Requirements for iron and docosahexaenoic acid (DHA) content of infant formula varies by country. Powdered full-term infant formula purchase data from all major physical stores in the US between 2017–2019 were obtained from CIRCANA, Inc. Iron and DHA composition and scoop sizes for [...] Read more.

Requirements for iron and docosahexaenoic acid (DHA) content of infant formula varies by country. Powdered full-term infant formula purchase data from all major physical stores in the US between 2017–2019 were obtained from CIRCANA, Inc. Iron and DHA composition and scoop sizes for each formula were obtained from manufacturers. The equivalent liquid ounces of prepared formula were calculated. Average iron and DHA content were compared between formula types and to both US and European formula composition requirements. These data represent 55.8 billion ounces of formula. The average iron content of all formula purchased was: 1.80 mg/100 kcal. This iron concentration is within the FDA regulations. However, it exceeds the maximum allowable iron concentration of infant formula (Stage 1) set by the European Commission of 1.3 mg/100 kcal. A total of 96% of formula purchased had an iron concentration of >1.3 mg/100 kcal. DHA is not a required ingredient in US formulas. The average DHA content of all formula purchased was: 12.6 mg/100 kcal. This DHA concentration is far below the minimum required DHA concentrations of infant formula (Stage 1) and follow-on formula (Stage 2) set by the European Commission of 20 mg/100 kcal. These are novel insights into the iron and DHA intake of formula-fed infants in the US. As international infant formulas have entered the US market due to the formula shortage, parents and providers need to be aware of regulatory differences in formula nutrient composition. Full article

(This article belongs to the Special Issue Effects of Breast Milk and Formula on Infant Intestinal Health and the Infant Gut Microbiome)

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