Gut Microbiome and Children’s Health

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Gut Microbiota".

Deadline for manuscript submissions: closed (15 January 2024) | Viewed by 21392

Special Issue Editors


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Guest Editor
Pediatric Specialty Laboratory, Arnold Palmer Hospital, Orlando Health, Orlando, FL 32806, USA
Interests: probiotics; prebiotics industry; molecular biology of infectious diseases
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Pediatric Gastroenterology, Hepatology and Nutrition Division, University of Miami Miller School of Medicine, Miami, FL 33136, USA
Interests: pediatric gastroenterology; functional bowel disorders; digestive disorders
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The role of the gut microbiome in health and disease reveals the potential link between the gut microbiome composition and diseases such as irritable bowel syndrome (IBS), Crohn’s disease, and celiac disease in humans. In the last few years, research has confirmed such a link, and several past and ongoing studies and clinical trials have aimed at exploring this relationship. Studies on the gut microbiota and host relationship have focused mostly on the adult population due to the ease of recruitment and the availability of subjects, while the recruitment of children in clinical trials or research studies is challenging. Children or young adults are considered an understudied population, although several gastrointestinal diseases develop in childhood and progress with age. This justifies the necessity of exploring the gut microbiome in children to address the problem before it worsens.  For example, children with functional abdominal pain disorders (FAPDs) showed a bacterial dysbiosis in gut microbiota at the phyla and genus levels compared to an age-matched healthy control group. The severity of FAPDs was found to correlate with some bacterial taxa in the collected stool samples. To better understand the impact of gut microbiota alterations in children or young adults, we propose this Special Issue of Microorganisms, which will cover gut microbiome alterations in different gastrointestinal diseases, bacterial dysbiosis in the gut microbiome of children, the role of different interventions in improving or altering gut microbiome composition, and the brain-gut axis. The interventions studied can include diet modifications, medications, integrative and complementary medicine approaches, pre- and probiotics consumption, and others. We welcome original research articles, reviews, and clinical trials.

Dr. Bassam Abomoelak
Dr. Miguel Saps
Guest Editors

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Keywords

  • gut microbiota
  • bacterial dysbiosis
  • gastrointestinal diseases
  • prebiotics
  • probiotics
  • fecal transplantation
  • brain-gut axis

Published Papers (10 papers)

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Research

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15 pages, 735 KiB  
Article
Association of the Infant Gut Microbiome with Temperament at Nine Months of Age: A Michigan Cohort Study
by Tengfei Ma, Sihan Bu, Adannaya C. Nzerem, Nigel Paneth, Jean M. Kerver, Cybil Nicole Cavalieri and Sarah S. Comstock
Microorganisms 2024, 12(1), 214; https://doi.org/10.3390/microorganisms12010214 - 20 Jan 2024
Viewed by 1092
Abstract
Though studies in animals and humans link the gut microbiota to brain development and control of behavior, little research has examined this connection in healthy infants. This prospective study could determine associations between infant gut microbiota at 3 months, and infant temperament at [...] Read more.
Though studies in animals and humans link the gut microbiota to brain development and control of behavior, little research has examined this connection in healthy infants. This prospective study could determine associations between infant gut microbiota at 3 months, and infant temperament at 9 months, in a prospective pregnancy cohort (Michigan Archive for Research on Child Health; n = 159). Microbiota profiling with 16S rRNA gene sequencing was conducted on fecal samples obtained at 3 months of age. Based on the relative abundance of gut microbiotas, three groups were identified, and each group was characterized by different microbes. Infant temperament outcomes were reported by mothers using the Infant Behavior Questionnaire-Revised Very Short Form at a mean age of 9.4 months. Fully adjusted multivariate linear regression models showed that certain clusters were associated with higher negative emotionality scores, prominently among infants who had poor vitamin D intake. However, no associations were evident between gut microbiota clusters and temperament scales after FDR correction. After using three differential abundance tools, Firmicutes was associated with higher positive affect/surgency scores, whereas Clostridioides was associated with lower scores. An association between the gut microbiota and early infancy temperament was observed; thus, this study warrants replication, with a particular focus on vitamin D moderation. Full article
(This article belongs to the Special Issue Gut Microbiome and Children’s Health)
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17 pages, 868 KiB  
Article
Associations of Plastic Bottle Exposure with Infant Growth, Fecal Microbiota, and Short-Chain Fatty Acids
by Curtis Tilves, Heather Jianbo Zhao, Moira K. Differding, Mingyu Zhang, Tiange Liu, Cathrine Hoyo, Truls Østbye, Sara E. Benjamin-Neelon and Noel T. Mueller
Microorganisms 2023, 11(12), 2924; https://doi.org/10.3390/microorganisms11122924 - 05 Dec 2023
Viewed by 1176
Abstract
Background/Objectives: Murine models show that plastics, via their chemical constituents (e.g., phthalates), influence microbiota, metabolism, and growth. However, research on plastics in humans is lacking. Here, we examine how the frequency of plastic bottle exposure is associated with fecal microbiota, short-chain fatty acids [...] Read more.
Background/Objectives: Murine models show that plastics, via their chemical constituents (e.g., phthalates), influence microbiota, metabolism, and growth. However, research on plastics in humans is lacking. Here, we examine how the frequency of plastic bottle exposure is associated with fecal microbiota, short-chain fatty acids (SCFAs), and anthropometry in the first year of life. Subjects/Methods: In 442 infants from the prospective Nurture birth cohort, we examined the association of frequency of plastic bottle feeding at 3 months with anthropometric outcomes (skinfolds, length-for-age, and weight-for-length) at 12 months of age and growth trajectories between 3 and 12 months. Furthermore, in a subset of infants (n = 70) that contributed fecal samples at 3 months and 12 months of age, we examined plastic bottle frequency in relation to fecal microbiota composition and diversity (measured by 16S rRNA gene sequencing of V4 region), and fecal SCFA concentrations (quantified using gas chromatography mass spectrometry). Results: At 3 months, 67.6% of infants were plastic bottle fed at every feeding, 15.4% were exclusively breast milk fed, and 48.9% were exclusively formula fed. After adjustment for potential confounders, infants who were plastic bottle fed less than every feeding compared to those who were plastic bottle fed at every feeding at 3 months did not show differences in anthropometry over the first 12 months of life, save for lower length-for-age z-score at 12 months (adjusted β = −0.45, 95% CI: −0.76, −0.13). Infants who were plastic bottle fed less than every feeding versus every feeding had lower fecal microbiota alpha diversity at 3 months (mean difference for Shannon index: −0.59, 95% CI: −0.99, −0.20) and lower isovaleric acid concentration at 3 months (mean difference: −2.12 μmol/g, 95% CI: −3.64, −0.60), but these results were attenuated following adjustment for infant diet. Plastic bottle frequency was not strongly associated with microbiota diversity or SCFAs at 12 months after multivariable adjustment. Frequency of plastic bottle use was associated with differential abundance of some bacterial taxa, however, significance was not consistent between statistical approaches. Conclusions: Plastic bottle frequency at 3 months was not strongly associated with measures of adiposity or growth (save for length-for-age) over the first year of life, and while plastic bottle use was associated with some features of fecal microbiota and SCFAs in the first year, these findings were attenuated in multivariable models with infant diet. Future research is needed to assess health effects of exposure to other plastic-based products and objective measures of microplastics and plastic constituents like phthalates. Full article
(This article belongs to the Special Issue Gut Microbiome and Children’s Health)
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13 pages, 2009 KiB  
Article
Changes in Microbiota Profile in the Proximal Remnant Intestine in Infants Undergoing Surgery Requiring Enterostomy
by Inês Barreiros-Mota, João R. Araújo, Cláudia Marques, Laura Sousa, Juliana Morais, Inês Castela, Ana Faria, Maria Teresa Neto, Gonçalo Cordeiro-Ferreira, Daniel Virella, Ana Pita, Luís Pereira-da-Silva and Conceição Calhau
Microorganisms 2023, 11(10), 2482; https://doi.org/10.3390/microorganisms11102482 - 03 Oct 2023
Viewed by 835
Abstract
Early-life gut dysbiosis has been associated with an increased risk of inflammatory, metabolic, and immune diseases later in life. Data on gut microbiota changes in infants undergoing intestinal surgery requiring enterostomy are scarce. This prospective cohort study examined the enterostomy effluent of 29 [...] Read more.
Early-life gut dysbiosis has been associated with an increased risk of inflammatory, metabolic, and immune diseases later in life. Data on gut microbiota changes in infants undergoing intestinal surgery requiring enterostomy are scarce. This prospective cohort study examined the enterostomy effluent of 29 infants who underwent intestinal surgery due to congenital malformations of the gastrointestinal tract, necrotizing enterocolitis, or spontaneous intestinal perforation. Initial effluent samples were collected immediately after surgery and final effluent samples were collected three weeks later. Gut microbiota composition was analysed using real-time PCR and 16S rRNA gene sequencing. Three weeks after surgery, an increase in total bacteria number (+21%, p = 0.026), a decrease in Staphylococcus (−21%, p = 0.002) and Candida spp. (−16%, p = 0.045), and an increase in Lactobacillus (+3%, p = 0.045) and in less abundant genera belonging to the Enterobacteriales family were found. An increase in alpha diversity (Shannon’s and Simpson’s indexes) and significant alterations in beta diversity were observed. A correlation of necrotizing enterocolitis with higher Staphylococcus abundance and higher alpha diversity was also observed. H2-blockers and/or proton pump inhibitor therapy were positively correlated with a higher total bacteria number. In conclusion, these results suggest that positive changes occur in the gut microbiota profile of infants three weeks after intestinal surgery. Full article
(This article belongs to the Special Issue Gut Microbiome and Children’s Health)
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17 pages, 9966 KiB  
Article
Mechanisms of Lung and Intestinal Microbiota and Innate Immune Changes Caused by Pathogenic Enterococcus Faecalis Promoting the Development of Pediatric Pneumonia
by Zhiying Tian, Ting Deng, Xuwen Gui, Leilei Wang, Qiulong Yan and Liang Wang
Microorganisms 2023, 11(9), 2203; https://doi.org/10.3390/microorganisms11092203 - 31 Aug 2023
Cited by 1 | Viewed by 1098
Abstract
Bacterial pneumonia is the main cause of illness and death in children under 5 years old. We isolated and cultured pathogenic bacteria LE from the intestines of children with pneumonia and replicated the pediatric pneumonia model using an oral gavage bacterial animal model. [...] Read more.
Bacterial pneumonia is the main cause of illness and death in children under 5 years old. We isolated and cultured pathogenic bacteria LE from the intestines of children with pneumonia and replicated the pediatric pneumonia model using an oral gavage bacterial animal model. Interestingly, based on 16srRNA sequencing, we found that the gut and lung microbiota showed the same imbalance trend, which weakened the natural resistance of this area. Further exploration of its mechanism revealed that the disruption of the intestinal mechanical barrier led to the activation of inflammatory factors IL-6 and IL-17, which promoted the recruitment of ILC-3 and the release of IL-17 and IL-22, leading to lung inflammation. The focus of this study is on the premise that the gut and lung microbiota exhibit similar destructive changes, mediating the innate immune response to promote the occurrence of pneumonia and providing a basis for the development and treatment of new drugs for pediatric pneumonia. Full article
(This article belongs to the Special Issue Gut Microbiome and Children’s Health)
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12 pages, 4514 KiB  
Article
HLA-Haplotypes Influence Microbiota Structure in Northwestern Mexican Schoolchildren Predisposed for Celiac Disease or Type 1 Diabetes
by Sandra V. Aguayo-Patrón, Omar A. Trujillo-Rivera, Fernanda Cornejo-Granados, Adrian Ochoa-Leyva and Ana M. Calderón de la Barca
Microorganisms 2023, 11(6), 1412; https://doi.org/10.3390/microorganisms11061412 - 27 May 2023
Cited by 2 | Viewed by 1560
Abstract
To contribute to and elucidate the participation of microbiota in celiac disease (CD) and type 1 diabetes (T1D) development, we evaluated the influence of HLA haplotypes, familial risk, and diet on the microbiota of schoolchildren. We conducted a cross-sectional study on 821 apparently [...] Read more.
To contribute to and elucidate the participation of microbiota in celiac disease (CD) and type 1 diabetes (T1D) development, we evaluated the influence of HLA haplotypes, familial risk, and diet on the microbiota of schoolchildren. We conducted a cross-sectional study on 821 apparently healthy schoolchildren, genotyping HLA DQ2/DQ8, and registering familial risk. We analyzed the fecal microbiota using 16S rRNA gene sequencing, and autoantibodies for CD or T1D by ELISA. After analyses, we created three groups: at-high-risk children (Group 1), at-high-risk children plus autoantibodies (Group 2), and nonrisk children (Group 3). HLA influenced the microbiota of Groups 1 and 2, decreasing phylogenetic diversity in comparison to Group 3. The relative abundance of Oscillospiraceae UCG_002, Parabacteroides, Akkermansia, and Alistipes was higher in Group 3 compared to Groups 1 and 2. Moreover, Oscillospiraceae UCG_002 and Parabacteroides were protectors of the autoantibodies’ positivity (RRR = 0.441 and RRR = 0.034, respectively). Conversely, Agathobacter was higher in Group 2, and Lachnospiraceae was in both Groups 1 and 2. Lachnospiraceae correlated positively with the sucrose degradation pathway, while the principal genera in Group 3 were associated with amino acid biosynthesis pathways. In summary, HLA and familial risk influence microbiota composition and functionality in children predisposed to CD or T1D, increasing their autoimmunity risk. Full article
(This article belongs to the Special Issue Gut Microbiome and Children’s Health)
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Review

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20 pages, 1141 KiB  
Review
Exploring the Mechanistic Interplay between Gut Microbiota and Precocious Puberty: A Narrative Review
by Min Yue and Lei Zhang
Microorganisms 2024, 12(2), 323; https://doi.org/10.3390/microorganisms12020323 - 04 Feb 2024
Viewed by 1284
Abstract
The gut microbiota has been implicated in the context of sexual maturation during puberty, with discernible differences in its composition before and after this critical developmental stage. Notably, there has been a global rise in the prevalence of precocious puberty in recent years, [...] Read more.
The gut microbiota has been implicated in the context of sexual maturation during puberty, with discernible differences in its composition before and after this critical developmental stage. Notably, there has been a global rise in the prevalence of precocious puberty in recent years, particularly among girls, where approximately 90% of central precocious puberty cases lack a clearly identifiable cause. While a link between precocious puberty and the gut microbiota has been observed, the precise causality and underlying mechanisms remain elusive. This narrative review aims to systematically elucidate the potential mechanisms that underlie the intricate relationship between the gut microbiota and precocious puberty. Potential avenues of exploration include investigating the impact of the gut microbiota on endocrine function, particularly in the regulation of hormones, such as gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Additionally, this review will delve into the intricate interplay between the gut microbiome, metabolism, and obesity, considering the known association between obesity and precocious puberty. This review will also explore how the microbiome’s involvement in nutrient metabolism could impact precocious puberty. Finally, attention is given to the microbiota’s ability to produce neurotransmitters and neuroactive compounds, potentially influencing the central nervous system components involved in regulating puberty. By exploring these mechanisms, this narrative review seeks to identify unexplored targets and emerging directions in understanding the role of the gut microbiome in relation to precocious puberty. The ultimate goal is to provide valuable insights for the development of non-invasive diagnostic methods and innovative therapeutic strategies for precocious puberty in the future, such as specific probiotic therapy. Full article
(This article belongs to the Special Issue Gut Microbiome and Children’s Health)
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12 pages, 763 KiB  
Review
Review and Perspectives on Bifidobacterium lactis for Infants’ and Children’s Health
by Annie Tremblay, Stéphane Bronner and Sylvie Binda
Microorganisms 2023, 11(10), 2501; https://doi.org/10.3390/microorganisms11102501 - 05 Oct 2023
Cited by 2 | Viewed by 1878
Abstract
The influence of microbiota dysbiosis in early life is increasingly recognized as a risk factor for the development of several chronic diseases later in life, including an increased risk of asthma, eczema, allergies, obesity, and neurodevelopmental disorders. The question whether the potential lifelong [...] Read more.
The influence of microbiota dysbiosis in early life is increasingly recognized as a risk factor for the development of several chronic diseases later in life, including an increased risk of asthma, eczema, allergies, obesity, and neurodevelopmental disorders. The question whether the potential lifelong consequences of early life dysbiosis could be mitigated by restoring microbiota composition remains unresolved. However, the current evidence base suggests that protecting the normal development of the microbiome during this critical developmental window could represent a valuable public health strategy to curb the incidence of chronic and lifestyle-related diseases. Probiotic Bifidobacteria are likely candidates for this purpose in newborns and infants considering the natural dominance of this genus on microbiota composition in early life. Moreover, the most frequently reported microbiota composition alteration in association with newborn and infant diseases, including necrotizing enterocolitis and diarrhea, is a reduction in Bifidobacteria levels. Several studies have assessed the effects of B. animalis subsp. lactis strains in newborns and infants, but recent expert opinions recommend analyzing their efficacy at the strain-specific level. Hence, using the B94 strain as an example, this review summarizes the clinical evidence available in infants and children in various indications, discussing the safety and potential modes of actions while providing perspectives on the concept of “non-infant-type” probiotics for infants’ health. Full article
(This article belongs to the Special Issue Gut Microbiome and Children’s Health)
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17 pages, 1133 KiB  
Review
The Gut-Wrenching Effects of Cryptosporidiosis and Giardiasis in Children
by Mayuri Prabakaran, Lyssa J. Weible, Joshua D. Champlain, Ryan Ye Jiang, Katalina Biondi, Ana A. Weil, Wesley C. Van Voorhis and Kayode K. Ojo
Microorganisms 2023, 11(9), 2323; https://doi.org/10.3390/microorganisms11092323 - 15 Sep 2023
Cited by 1 | Viewed by 3428
Abstract
Cryptosporidium species and Giardia duodenalis are infectious intestinal protozoan pathogens that cause alarming rates of morbidity and mortality worldwide. Children are more likely to have clinical symptoms due to their less developed immune systems and factors such as undernutrition, especially in low- and [...] Read more.
Cryptosporidium species and Giardia duodenalis are infectious intestinal protozoan pathogens that cause alarming rates of morbidity and mortality worldwide. Children are more likely to have clinical symptoms due to their less developed immune systems and factors such as undernutrition, especially in low- and middle-income countries. The severity of the symptoms and clinical manifestations in children may vary from asymptomatic to life-threatening depending on the Cryptosporidium species/G. duodenalis strains and the resulting complex stepwise interactions between the parasite, the host nutritional and immunologic status, and the gut microbiome profile. Structural damages inflicted by both parasites to epithelial cells in the large and small intestines could severely impair children’s gut health, including the ability to absorb nutrients, resulting in stunted growth, diminished neurocognitive development, and other long-term effects. Clinically approved cryptosporidiosis and giardiasis drugs have broad antimicrobial effects that have incomprehensible impacts on growing children’s gut health. Full article
(This article belongs to the Special Issue Gut Microbiome and Children’s Health)
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17 pages, 960 KiB  
Review
Gut Microbiome and Neurodevelopmental Disorders: A Link Yet to Be Disclosed
by Zoi Iliodromiti, Anastasia-Rafaella Triantafyllou, Marina Tsaousi, Abraham Pouliakis, Chrysa Petropoulou, Rozeta Sokou, Paraskevi Volaki, Theodora Boutsikou and Nicoletta Iacovidou
Microorganisms 2023, 11(2), 487; https://doi.org/10.3390/microorganisms11020487 - 15 Feb 2023
Cited by 11 | Viewed by 3971
Abstract
Τhe importance of the gut microbiome and its functions has only recently been recognized and researched in greater depth. The establishment of the human gut microbiome begins in utero, forming its adult-like phenotype in the first 2–3 years of life. Several factors affect [...] Read more.
Τhe importance of the gut microbiome and its functions has only recently been recognized and researched in greater depth. The establishment of the human gut microbiome begins in utero, forming its adult-like phenotype in the first 2–3 years of life. Several factors affect and alter the gut microbiome composition and its metabolic functions, such as early onset of breastfeeding, mode of delivery, antibiotic administration, or exposure to chemical substances, among others. Existing data support the important connection between health status and gut microbiome homeostasis. In cases when this balance is disturbed, several disorders may arise, such as inflammatory reactions that lead to atopy, eczema, or allergic asthma. The so-called gut-brain axis refers to the complex biochemical pathways between the central nervous system and the gastrointestinal system. One of the most fascinating areas of ongoing research is the broad spectrum of neurodevelopmental disorders (NDDs) and how gut health may be associated with such disorders. The prevalence of NDDs, such as autism spectrum disorder or attention deficit hyperactivity disorder, has increased over recent years. Whether gut microbiota homeostasis plays a role in these disorders is not yet fully understood. The aim of this narrative review is to provide an account of current knowledge on how gut health is linked with these disorders. We performed a literature review in order to identify and synthesize available data that highlights the potential association between NDDs and a balanced gut microbiome in terms of composition and proper function. The connection between the gut microbiome and NDDs offers promising new opportunities for future research. Full article
(This article belongs to the Special Issue Gut Microbiome and Children’s Health)
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29 pages, 1051 KiB  
Review
The Gut Microbiome of Children during the COVID-19 Pandemic
by Mickayla Bacorn, Hector N. Romero-Soto, Shira Levy, Qing Chen and Suchitra K. Hourigan
Microorganisms 2022, 10(12), 2460; https://doi.org/10.3390/microorganisms10122460 - 13 Dec 2022
Cited by 3 | Viewed by 3502
Abstract
The gut microbiome has been shown to play a critical role in maintaining a healthy state. Dysbiosis of the gut microbiome is involved in modulating disease severity and potentially contributes to long-term outcomes in adults with COVID-19. Due to children having a significantly [...] Read more.
The gut microbiome has been shown to play a critical role in maintaining a healthy state. Dysbiosis of the gut microbiome is involved in modulating disease severity and potentially contributes to long-term outcomes in adults with COVID-19. Due to children having a significantly lower risk of severe illness and limited sample availability, much less is known about the role of the gut microbiome in children with COVID-19. It is well recognized that the developing gut microbiome of children differs from that of adults, but it is unclear if this difference contributes to the different clinical presentations and complications. In this review, we discuss the current knowledge of the gut microbiome in children with COVID-19, with gut microbiome dysbiosis being found in pediatric COVID-19 but specific taxa change often differing from those described in adults. Additionally, we discuss possible mechanisms of how the gut microbiome may mediate the presentation and complications of COVID-19 in children and the potential role for microbial therapeutics. Full article
(This article belongs to the Special Issue Gut Microbiome and Children’s Health)
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