A pilot study to disentangle the infant gut microbiota composition and identification of bacteria correlates with high fat mass

Abstract

Background: At birth, the human intestine is colonized by a complex community of microorganisms known as gut microbiota. These complex microbial communities that inhabit the gut microbiota are thought to play a key role in maintaining host physiological homeostasis. For this reason, correct colonization of the gastrointestinal tract in the early stages of life could be fundamental for human health. Furthermore, alterations of the infant microbiota are correlated with the development of human inflammatory diseases and disorders. In this context, the possible relationships between intestinal microbiota and body composition during infancy are of great interest.

Methods: In this study, we have performed a pilot study based on 16S rRNA gene profiling and metagenomic approaches on repeatedly measured data on time involving a cohort of 41 Italian newborns, which is aimed to investigate the possible correlation between body fat mass percentage (FM%) and the infant gut microbiota composition.

Results and conclusion: The taxonomical analysis of the stool microbiota of each infant included in the cohort allowed the identification of a specific correlation between intestinal bacteria, such as Bifidobacterium and Veillonella, and the increase in FM%. Moreover, the analysis of the infant microbiome’s metabolic capabilities suggested that the intestinal microbiome functionally impacts the human host and its possible influence on host physiology.

Keywords

Infant gut microbiota / microbiome / fat mass % / body weight

References

[1] Milani C,Bottacini F.The first microbial colonizers of the human gut: composition, activities, and health implications of the infant gut microbiota.Microbiol Mol Biol Rev2017;81:e00036-17 PMCID:PMC5706746

[2] Rooks MG.Gut microbiota, metabolites and host immunity.Nat Rev Immunol2016;16:341-52 PMCID:PMC5541232

[3] Zheng D,Elinav E.Interaction between microbiota and immunity in health and disease.Cell Res2020;30:492-506 PMCID:PMC7264227

[4] Valdes AM,Segal E.Role of the gut microbiota in nutrition and health.Brit Med J2018;361:k2179 PMCID:PMC6000740

[5] Dahl WJ,Lambert JM.Diet, nutrients and the microbiome.Prog Mol Biol Transl Sci2020;171:237-63

[6] Fassarella M,Penders J,Smidt H.Gut microbiome stability and resilience: elucidating the response to perturbations in order to modulate gut health.Gut2021;70:595-605

[7] Reyman M,van Baarle D.Impact of delivery mode-associated gut microbiota dynamics on health in the first year of life.Nat Commun2019;10:4997 PMCID:PMC6825150

[8] Zhang C,Jin B.The effects of delivery mode on the gut microbiota and health: state of art.Front Microbiol2021;12:724449 PMCID:PMC8733716

[9] Mancabelli L,Milani C.Multi-population cohort meta-analysis of human intestinal microbiota in early life reveals the existence of infant community state types (ICSTs).Comput Struct Biotechnol J2020;18:2480-93 PMCID:PMC7516180

[10] Ventura M,Lugli GA.Health benefits conferred by the human gut microbiota during infancy.Microb Biotechnol2019;12:243-8 PMCID:PMC6389842

[11] Turroni F,Ventura M.The human gut microbiota during the initial stages of life: insights from bifidobacteria.Curr Opin Biotechnol2022;73:81-7

[12] Yao Y,Ye Y,Chen F.The role of microbiota in infant health: from early life to adulthood.Front Immunol2021;12:708472 PMCID:PMC8529064

[13] Browne HP,Lawley TD.Mother-infant transmission of human microbiota.Curr Opin Microbiol2022;69:102173

[14] Hoang DM,Vandenplas Y.The impact of caesarean section on the infant gut microbiome.Acta Paediatr2021;110:60-7

[15] Callaway E.C-section babies are missing key microbes.Nature2019;

[16] Gregory KE,Natale KM,Van Marter LJ.Necrotizing enterocolitis in the premature infant: neonatal nursing assessment, disease pathogenesis, and clinical presentation.Adv Neonatal Care2011;11:155-64; quiz 165 PMCID:PMC3759524

[17] Baranowski JR.Necrotizing enterocolitis and the preterm infant microbiome.Adv Exp Med Biol2019;1125:25-36

[18] El Manouni El Hassani S,Berkhout DJC.Profound pathogen-specific alterations in intestinal microbiota composition precede late-onset sepsis in preterm infants: a longitudinal, multicenter, case-control study.Clin Infect Dis2021;73:e224-32

[19] Liu Y,Zhai S,Liu C.Gut microbiota and atopic dermatitis in children: a scoping review.BMC Pediatr2022;22:323 PMCID:PMC9161518

[20] Yu L,Huang YH,Guo Y.Comparison of gut microbiota between infants with atopic dermatitis and healthy controls in Guangzhou, China.J Asthma Allergy2021;14:493-500 PMCID:PMC8121685

[21] Reddel S,Quagliariello A.Gut microbiota profile in children affected by atopic dermatitis and evaluation of intestinal persistence of a probiotic mixture.Sci Rep2019;9:4996 PMCID:PMC6428866

[22] Cong X,Xu W.Influence of feeding type on gut microbiome development in hospitalized preterm infants.Nurs Res2017;66:123-33 PMCID:PMC5334772

[23] Parra-Llorca A,Alcántara C.Preterm gut microbiome depending on feeding type: significance of donor human milk.Front Microbiol2018;9:1376 PMCID:PMC6030370

[24] Guaraldi F.Effect of breast and formula feeding on gut microbiota shaping in newborns.Front Cell Infect Microbiol2012;2:94 PMCID:PMC3472256

[25] Unger S,Shah P,O’Connor DL.Gut microbiota of the very-low-birth-weight infant.Pediatr Res2015;77:205-13 PMCID:PMC7094749

[26] Alderete TL,Shaffer JP.Early life gut microbiota is associated with rapid infant growth in Hispanics from Southern California.Gut Microbes2021;13:1961203 PMCID:PMC8386720

[27] Luoto R,Laitinen K.The impact of perinatal probiotic intervention on the development of overweight and obesity: follow-up study from birth to 10 years.Int J Obes2010;34:1531-7

[28] Chouraqui JP,Labaune JM.Assessment of the safety, tolerance, and protective effect against diarrhea of infant formulas containing mixtures of probiotics or probiotics and prebiotics in a randomized controlled trial.Am J Clin Nutr2008;87:1365-73

[29] Soderborg TK,Mulligan CE.The gut microbiota in infants of obese mothers increases inflammation and susceptibility to NAFLD.Nat Commun2018;9:4462 PMCID:PMC6203757

[30] Koleva PT,Kozyrskyj AL.The infant gut microbiome: evidence for obesity risk and dietary intervention.Nutrients2015;7:2237-60 PMCID:PMC4425142

[31] Roggero P,Amato O.Evaluation of air-displacement plethysmography for body composition assessment in preterm infants.Pediatr Res2012;72:316-20

[32] Mancabelli L,Fontana F.Untangling the link between the human gut microbiota composition and the severity of the symptoms of the COVID-19 infection.Environ Microbiol2022;24:6453-62 PMCID:PMC9538590

[33] Milani C,Foroni E.Assessing the fecal microbiota: an optimized ion torrent 16S rRNA gene-based analysis protocol.PLoS One2013;8:e68739 PMCID:PMC3711900

[34] Bolyen E,Dillon MR.Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2.Nat Biotechnol2019;37:852-7 PMCID:PMC7015180

[35] Caporaso JG,Stombaugh J.QIIME allows analysis of high-throughput community sequencing data.Nat Methods2010;7:335-6 PMCID:PMC3156573

[36] Milani C,Lugli GA.Tracing mother-infant transmission of bacteriophages by means of a novel analytical tool for shotgun metagenomic datasets: METAnnotatorX.Microbiome2018;6:145 PMCID:PMC6102903

[37] Milani C,Fontana F.METAnnotatorX2: a comprehensive tool for deep and shallow metagenomic data set analyses.mSystems2021;6:e0058321 PMCID:PMC8269244

[38] Langmead B.Fast gapped-read alignment with bowtie 2.Nat Methods2012;9:357-9 PMCID:PMC3322381

[39] Langmead B,Antonescu V.Scaling read aligners to hundreds of threads on general-purpose processors.Bioinformatics2019;35:421-32 PMCID:PMC6361242

[40] Chen Y,Zhang Y.High speed BLASTN: an accelerated MegaBLAST search tool.Nucleic Acids Res2015;43:7762-8 PMCID:PMC4652774

[41] Caspi R,Ferrer L.The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of pathway/genome databases.Nucleic Acids Res2016;44:D471-80 PMCID:PMC4702838

[42] Zhao Y,Ye Y.RAPSearch2: a fast and memory-efficient protein similarity search tool for next-generation sequencing data.Bioinformatics2012;28:125-6 PMCID:PMC3244761

[43] Ye Y,Tang H.RAPSearch: a fast protein similarity search tool for short reads.BMC Bioinformatics2011;12:159 PMCID:PMC3113943

[44] Spearman's rank correlation coefficient.BMJ2018;362:k4131

[45] Benjamini Y,Elmer G,Golani I.Controlling the false discovery rate in behavior genetics research.Behav Brain Res2001;125:279-84

[46] Rutayisire E,Liu Y.The mode of delivery affects the diversity and colonization pattern of the gut microbiota during the first year of infants’ life: a systematic review.BMC Gastroenterol2016;16:86 PMCID:PMC4967522

[47] Alessandri G,Mancabelli L.Exploring species-level infant gut bacterial biodiversity by meta-analysis and formulation of an optimized cultivation medium.NPJ Biofilms Microbiomes2022;8:88 PMCID:PMC9622858

[48] Matharu D,Dikareva E.Bacteroides abundance drives birth mode dependent infant gut microbiota developmental trajectories.Front Microbiol2022;13:953475 PMCID:PMC9583133

[49] Mitchell CM,Hogstrom L.Delivery mode affects stability of early infant gut microbiota.Cell Rep Med2020;1:100156 PMCID:PMC7762768

[50] Gao X,Xue J.Body mass index differences in the gut microbiota are gender specific.Front Microbiol2018;9:1250 PMCID:PMC6023965

[51] Lv Y,Jia H,Sun W.The association between gut microbiota composition and BMI in Chinese male college students, as analysed by next-generation sequencing.Br J Nutr2019;122:986-95

[52] Kim MH,Kim J.Gut microbiota and metabolic health among overweight and obese individuals.Sci Rep2020;10:19417 PMCID:PMC7655835

[53] Palmas V,Madau V.Gut microbiota markers associated with obesity and overweight in Italian adults.Sci Rep2021;11:5532 PMCID:PMC7943584

[54] Ignacio A,Rodrigues VA.Correlation between body mass index and faecal microbiota from children.Clin Microbiol Infect2016;22:258.e1-8

[55] Greathouse KL,Padgett RN.Gut microbiome meta-analysis reveals dysbiosis is independent of body mass index in predicting risk of obesity-associated CRC.BMJ Open Gastroenterol2019;6:e000247 PMCID:PMC6398873

[56] Barratt MJ,Ahsan K.Bifidobacterium infantis treatment promotes weight gain in Bangladeshi infants with severe acute malnutrition.Sci Transl Med2022;14:eabk1107 PMCID:PMC9516695

[57] Michael DR,Masetti G.A randomised controlled study shows supplementation of overweight and obese adults with lactobacilli and bifidobacteria reduces bodyweight and improves well-being.Sci Rep2020;10:4183 PMCID:PMC7060206

[58] Alessandri G,Tarracchini C.Disclosing the genomic diversity among members of the bifidobacterium genus of canine and feline origin with respect to those from human.Appl Environ Microbiol2022;88:e0203821 PMCID:PMC9004377

[59] Turroni F,Duranti S.The infant gut microbiome as a microbial organ influencing host well-being.Ital J Pediatr2020;46:16 PMCID:PMC7003403

[60] Tanaka M.Development of the gut microbiota in infancy and its impact on health in later life.Allergol Int2017;66:515-22

[61] van Beijsterveldt IALP, de Fluiter KS, Breij LM, van der Steen M, Hokken-Koelega ACS. Fat mass and fat-free mass track from infancy to childhood: new insights in body composition programming in early life.Obesity2021;29:1899-906 PMCID:PMC9292756

[62] Leunissen RW,Stijnen T.Timing and tempo of first-year rapid growth in relation to cardiovascular and metabolic risk profile in early adulthood.J Am Med Assoc2009;301:2234-42

[63] de Fluiter KS, van Beijsterveldt IALP, Breij LM, Acton D, Hokken-Koelega ACS. Association between fat mass in early life and later fat mass trajectories.JAMA Pediatr2020;174:1141-8 PMCID:PMC7432277