Metabolic Disease: Obesity, Malnutrition, and Intestinal Microbiota

Abstract

Obesity is a worldwide epidemic that is accompanied by a dramatic increase in obesity-related disorders; it threatens both industrialized and developing countries. Recent studies have shown that the gut microbial community (microbiota) is an environmental factor of developmental origins of health and diseases (DOHaD) that regulates obesity by increasing energy harvest from the diet and regulating peripheral metabolism.

Dysbiosis in neonates and infants is caused by a disrupted environment that influences the initial colonization of microbes in the gut; such disruptions include a C-section delivery, formula feeding, excessive use of antibiotics, or the introduction of inappropriate solid foods containing a high amount of saturated fat. Dysbiosis delays the development of mucosal host defense and immunity, leading to a high risk of obesity, metabolic disease, and immune-mediated disease later in life. Bifidobacteria and Bacteroides, which are found in human milk and are predominant mutualists in healthy microbiota, colonize the gut initially as “pioneer” bacteria; in this way, human milk and its oligosaccharides confer benefits, such as reducing the risks of obesity and metabolic syndrome, to the offspring. As the microbial exposure of neonates is provided mainly from the maternal microbiota, maternal obesity with dysbiosis has an impact on infant microbiota development that can lead to major shifts in the microbiota composition of the child in early life and may cause aberrant immune function and priming for harmful responses to postnatal triggers. Alterations in the gut microbiome have been strongly implicated in childhood malnutrition. This paper reviews the evidence linking gut microbiota, obesity, and malnutrition.

Keywords

obesity - dysbiosis - gut microbiota - intestinal colonization - malnutrition - delivery mode - maternal obesity

• References

• 1 Cheng MH. Asia-Pacific faces diabetes challenge. Lancet 2010; 375 (9733) 2207-2210
• 2 Han JC, Lawlor DA, Kimm SY. Childhood obesity. Lancet 2010; 375 (9727) 1737-1748
• 3 Weiss R, Kaufman FR. Metabolic complications of childhood obesity: identifying and mitigating the risk. Diabetes Care 2008; 31 (Suppl. 02) S310-S316
• 4 Ebbeling CB, Pawlak DB, Ludwig DS. Childhood obesity: public-health crisis, common sense cure. Lancet 2002; 360 (9331) 473-482
• 5 Ley RE, Bäckhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI. Obesity alters gut microbial ecology. Proc Natl Acad Sci U S A 2005; 102 (31) 11070-11075
• 6 Cani PD, Bibiloni R, Knauf C , et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 2008; 57 (6) 1470-1481
• 7 Miller AL, Lee HJ, Lumeng JC. Obesity-associated biomarkers and executive function in children. Pediatr Res 2015; 77 (1–2) 143-147
• 8 Yoshimoto S, Loo TM, Atarashi K , et al. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature 2013; 499 (7456) 97-101
• 9 Nieuwdorp M, Gilijamse PW, Pai N, Kaplan LM. Role of the microbiome in energy regulation and metabolism. Gastroenterology 2014; 146 (6) 1525-1533
• 10 Barker DJ. The developmental origins of adult disease. Eur J Epidemiol 2003; 18 (8) 733-736
• 11 Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006; 444 (7122) 1027-1031
• 12 Black RE, Victora CG, Walker SP , et al; Maternal and Child Nutrition Study Group. Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet 2013; 382 (9890) 427-451
• 13 Kau AL, Ahern PP, Griffin NW, Goodman AL, Gordon JI. Human nutrition, the gut microbiome and the immune system. Nature 2011; 474 (7351) 327-336
• 14 Tsuji H, Oozeer R, Matsuda K , et al. Molecular monitoring of the development of intestinal microbiota in Japanese infants. Benef Microbes 2012; 3 (2) 113-125
• 15 Bearfield C, Davenport ES, Sivapathasundaram V, Allaker RP. Possible association between amniotic fluid micro-organism infection and microflora in the mouth. BJOG 2002; 109 (5) 527-533
• 16 Walker WA. Bacterial colonization, probiotics and the development of intestinal host defense. Funct Food Rev 2009; 1: 13-19
• 17 Artis D. Epithelial-cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut. Nat Rev Immunol 2008; 8 (6) 411-420
• 18 Shen L, Turner JR. Role of epithelial cells in initiation and propagation of intestinal inflammation. Eliminating the static: tight junction dynamics exposed. Am J Physiol Gastrointest Liver Physiol 2006; 290 (4) G577-G582
• 19 Frey A, Giannasca KT, Weltzin R , et al. Role of the glycocalyx in regulating access of microparticles to apical plasma membranes of intestinal epithelial cells: implications for microbial attachment and oral vaccine targeting. J Exp Med 1996; 184 (3) 1045-1059
• 20 Salzman NH, Ghosh D, Huttner KM, Paterson Y, Bevins CL. Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin. Nature 2003; 422 (6931) 522-526
• 21 Olivares M, Neef A, Castillejo G , et al. The HLA-DQ2 genotype selects for early intestinal microbiota composition in infants at high risk of developing coeliac disease. Gut 2015; 64 (3) 406-417
• 22 Moro E. Morphologische und biologische Untersuchung über die Darmbakterien des Säuglings. [Morphological and biological study of the intestinal bacteria of infants]. Jahrb F Kinderh 1905; 61: 687-734
• 23 Bode L. Recent advances on structure, metabolism, and function of human milk oligosaccharides. J Nutr 2006; 136 (8) 2127-2130
• 24 Barnes MJ, Powrie F. Immunology. The gut's Clostridium cocktail. Science 2011; 331 (6015) 289-290
• 25 Geuking MB, Cahenzli J, Lawson MA , et al. Intestinal bacterial colonization induces mutualistic regulatory T cell responses. Immunity 2011; 34 (5) 794-806
• 26 Rescigno M, Urbano M, Valzasina B , et al. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol 2001; 2 (4) 361-367
• 27 Schwartz S, Friedberg I, Ivanov IV , et al. A metagenomic study of diet-dependent interaction between gut microbiota and host in infants reveals differences in immune response. Genome Biol 2012; 13 (4) r32
• 28 Wang C, Shoji H, Sato H , et al. Effects of oral administration of bifidobacterium breve on fecal lactic acid and short-chain fatty acids in low birth weight infants. J Pediatr Gastroenterol Nutr 2007; 44 (2) 252-257
• 29 Sanz Y, Rastmanesh R, Agostoni C. Understanding the role of gut microbes and probiotics in obesity: how far are we?. Pharmacol Res 2013; 69 (1) 144-155
• 30 Verdam FJ, Fuentes S, de Jonge C , et al. Human intestinal microbiota composition is associated with local and systemic inflammation in obesity. Obesity (Silver Spring) 2013; 21 (12) E607-E615
• 31 Le Chatelier E, Nielsen T, Qin J , et al; MetaHIT consortium. Richness of human gut microbiome correlates with metabolic markers. Nature 2013; 500 (7464) 541-546
• 32 Bäckhed F, Manchester JK, Semenkovich CF, Gordon JI. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci U S A 2007; 104 (3) 979-984
• 33 Jumpertz R, Le DS, Turnbaugh PJ , et al. Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans. Am J Clin Nutr 2011; 94 (1) 58-65
• 34 Sanz Y, Olivares M, Moya-Pérez Á, Agostoni C. Understanding the role of gut microbiome in metabolic disease risk. Pediatr Res 2015; 77 (1–2) 236-244
• 35 Sato J, Kanazawa A, Ikeda F , et al. Gut dysbiosis and detection of “live gut bacteria” in blood of Japanese patients with type 2 diabetes. Diabetes Care 2014; 37 (8) 2343-2350
• 36 Patro B, Liber A, Zalewski B, Poston L, Szajewska H, Koletzko B. Maternal and paternal body mass index and offspring obesity: a systematic review. Ann Nutr Metab 2013; 63 (1–2) 32-41
• 37 Kristensen J, Vestergaard M, Wisborg K, Kesmodel U, Secher NJ. Pre-pregnancy weight and the risk of stillbirth and neonatal death. BJOG 2005; 112 (4) 403-408
• 38 Triunfo S, Lanzone A. Impact of overweight and obesity on obstetric outcomes. J Endocrinol Invest 2014; 37 (4) 323-329
• 39 Koren O, Goodrich JK, Cullender TC , et al. Host remodeling of the gut microbiome and metabolic changes during pregnancy. Cell 2012; 150 (3) 470-480
• 40 Collado MC, Isolauri E, Laitinen K, Salminen S. Effect of mother's weight on infant's microbiota acquisition, composition, and activity during early infancy: a prospective follow-up study initiated in early pregnancy. Am J Clin Nutr 2010; 92 (5) 1023-1030
• 41 Nagpal R, Ogata K, Tsuji H , et al. Differences in intestinal microbiota of infants between vaginal delivery and C-section, in particular alpha-toxigenic and enterotoxigenic C. perfringens. Paper presented at: the 4th Annual Meeting of the Society of Japan Development Origins of Health and Disease. August 2015
• 42 Nagpal R, Ogata K, Tsuji H , et al. Differences in intestinal microbiota of infants between vaginal delivery and C-section, in particular alpha-toxigenic and enterotoxigenic C. perfringens. The 42nd Annual Meeting of the Japanese Society for Pediatric Gastroenterology, Hepatology and Nutrition. October 2015
• 43 Darmasseelane K, Hyde MJ, Santhakumaran S, Gale C, Modi N. Mode of delivery and offspring body mass index, overweight and obesity in adult life: a systematic review and meta-analysis. PLoS ONE 2014; 9 (2) e87896
• 44 Gibbons L, Belizán JM, Lauer JA , et al. The global numbers and costs of additionally needed and unnecessary caesarean sections performed per year: overuse as a barrier to universal coverage. World Health Report, Background Paper, No 30; 2010
• 45 Gordon JI, Dewey KG, Mills DA, Medzhitov RM. The human gut microbiota and undernutrition. Sci Transl Med 2012; 4 (137) 137ps12
• 46 Subramanian S, Huq S, Yatsunenko T , et al. Persistent gut microbiota immaturity in malnourished Bangladeshi children. Nature 2014; 510 (7505) 417-421
• 47 Kane AV, Dinh DM, Ward HD. Childhood malnutrition and the intestinal microbiome. Pediatr Res 2015; 77 (1–2) 256-262
• 48 Kosek M, Bern C, Guerrant RL. The global burden of diarrhoeal disease, as estimated from studies published between 1992 and 2000. Bull World Health Organ 2003; 81 (3) 197-204
• 49 Yamashiro Y, Nagata S. Beneficial microbes for premature infants, and children with malignancy undergoing chemotherapy. Benef Microbes 2010; 1 (4) 357-365