1. Please check and comment entries here.
Table of Contents

    Topic review


    View times: 27
    Submitted by: Ishawu Iddrisu


    Malnutrition refers to deficiencies, excesses or imbalances in a person’s intake and/or use of energy and/or nutrients. Malnutrition in the form of undernutrition affects millions of people across the world, especially children living in developing countries. The major cause of malnutrition is inadequate access to food combined with infections causing diarrhoea. Recent advances in our understanding of the gut microbiota have shown a link between dietary intake and gut microbiota that may affect nutritional status; this suggests a potential link between the gut microbiota and malnutrition. Thus, intervention strategies that target the gut microbiota may offer an enhanced approach for combating malnutrition with respect to those traditionally employed (such as treatment with ready-to-use therapeutic food only). 

    1. Introduction

    The prevalence of malnutrition in children under five years of age in developing nations remains alarming. The World Health Organization (WHO), United Nations Children’s Fund (UNICEF) and the World Bank Group reported that globally in 2017, 150.8 million (22.2%) children under five years of age were stunted, with wasting threatening the lives of 7.5% (50.5 million) of children [1]. Africa and Asia are the continents most affected by such malnutrition, bearing 39% and 55% (respectively) of global stunting prevalence in children under five. It is estimated that about half of all under-five-year-old childhood deaths are as a result of stunting (chronic malnutrition), culminating in about 3 million child deaths every year [1]. The most common and immediate causes of malnutrition/undernutrition in children are inadequate dietary intake and disease (such as diarrhoea), according to the UNICEF conceptual framework of the causes of malnutrition [2], resulting in deficient growth and development. Although inadequate access to sufficient nutrition is the main cause of malnutrition, gut microbiota have also been implicated in this condition [3][4]. Alterations in the gut microbiota, characterized by increases in the phylum Proteobacteria and decreases in Bifidobacterium and Lactobacillus species, are associated with episodes of diarrhoea [5][6][7], and diarrhoea is a major causative factor in malnutrition of children, especially those in low-income countries [8][9]. The causes of malnutrition, together with strategies to counteract malnutrition, are of significant public health interest, and manipulation of the gut microbiota provides a potential opportunity for alleviation of malnutrition [10].

    2. The Human Gut Microbiome in Health and Disease

    2.1. In Health

    The human gastrointestinal tract harbours microbial populations consisting of 1013–1014 cells [11], but the density and composition differ markedly between compartments. In the stomach of healthy people, the bacterial load is relatively low at 102 colony-forming units (CFUs)/mL of contents, but rises in the small intestine to 102–104 CFUs/mL [12]. However, the highest levels (1012 CFUs/mL) are found in the colon, where conditions (pH 5.5–7, slow transit time, and high nutrient availability) are highly conducive for bacterial growth [13]. The colonic bacteria are mainly anaerobic [12] and carry out a range of metabolic processes, some of which are considered of benefit to the host. For example, gut microbes ferment indigestible carbohydrates, generating short-chain fatty acids (SCFAs) for the host. These SCFAs have been reported to have several health benefits to the host, including the provision of energy for epithelial cells and lowering the pH of the intestinal lumen, thus restricting growth of some pathogens [14][15] and providing an anti-inflammatory effect to the host [16]. The gut microbiota has also been observed to play an important role in absorption, storage and expenditure of energy from the diet [17][18][19] as well as synthesis of vitamins K and B12 [20][21]. Energy intake and expenditure are predominantly coordinated by the brain. The gastrointestinal tract (GI), the first site of contact with ingested food, sends important signals (through neuroendocrine and neuroimmune systems) to the brain regarding the composition and size of incoming food [22]. Furthermore, the gut microbiota is involved in the production of metabolites, including SCFAs, secondary bile acids, tryptophan and even neurotransmitters; these play an important role in gut barrier function and also in gut–brain signalling [23][24]. The gut–brain axis is important for maintaining energy balance and controlling energy expenditure, and has also been observed to impact on cognitive function [25]. Such benefits have led to a growing interest in the use of prebiotics, probiotics and other dietary modifications to modulate the gut microbiota to improve nutrition and health [26].
    The role of the gut microbiota of newborns in growth and development may be dependent on the acquired microbial composition [27]. Recent metagenomic analysis of the gut microbiota of infants suggests that in addition to the composition, the functional potential of the microbiota plays a significant role in the nutritional status of the infant. For instance, the development (transmitted from the mother) of bile acid and starch metabolism bacteria may impact nutrient absorption and therefore, affect growth and development of infants [28][29]. In breastfed infants, the gut microbiota is dominated by Bifidobacterium longum subsp. infantis, which is tailored towards the metabolism of human milk oligosaccharides (HMO) [30][31]. For infants fed on formula milk, infant formulae are commonly fortified with prebiotics so as to confer similar beneficial components as those found in breastmilk [32][33][34]. Prebiotics are “substrates that are selectively utilized by host microorganisms conferring health benefits to the host” [35]. The common prebiotics used in infant formula are short-chain galacto-oligosaccharides (GOS) and long-chain fructo-oligosaccharides (FOS). These prebiotics have been shown to beneficially alter the gut microbiota of infants by selectively enhancing the growth of Bifidobacterium and lowering the abundance of Enterococcus and Escherichia coli [36][37]. However, GOS and FOS are structurally different from HMO [38] and so do not entirely replicate the beneficial effects of HMOs on the infant gut microbiota, for example, on a species level [34][39][40]. Nevertheless, it has been noted that an infant diet supported by prebiotic formula results in fewer infections than a placebo formula does, and so non-HMO prebiotics appear to have a positive impact in infants [41].
    Probiotics are defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host” [42]. It is now well established that probiotics can modulate the gut microbiota of the host in a beneficial fashion [43][44][45]. For instance, the addition of probiotics to infant formula has been known to confer numerous benefits to the infant, including the improvement of gut health and immunity, countering the growth of harmful bacteria (pathogens) in the gut and enhancing overall host immune and health status [43]. Moreover, the addition of probiotics including Lactobacillus reuteri, Lactobacillus acidophilus, Bifidobacterium longum, Bacillus clausii and Bifidobacterium lactis in infant formula has been shown to reduce risks associated with diarrhoea resulting from antibiotic use and the symptoms of colic [46][47][48]. In contrast, numerous studies have failed to find any effect of probiotics on diarrhoea outcomes in children [39][49][50]. Indeed, a recent Cochrane review based on large clinical trials with low risk of bias [51] reported little or no effect of probiotics in the reduction of diarrhoea. Such contradictory results are likely linked to the use of different probiotics and target populations. Given the contrasting evidence on the use of probiotics in the management of diarrhoea in children, there remains a need for targeted large-scale trials to follow on from the promising findings of specific probiotics that improve diarrhoea outcomes, especially in children.

    2.2. In Disease

    There is evidence linking the gut microbial community to a range of diseases and disorders, including inflammatory bowel disease (IBD), mood disorders, obesity, autism and psoriatic arthritis [52][53][54][55][56][57], though further research is needed to ascertain the causal link between the gut microbiota and such diseases. In some of these conditions, interventions that impact the gut microbial community have led to improvement of symptoms, further supporting a role for the microbiota [58][59][60]. An altered gut microbiota can be caused by environmental factors such as antibiotic use, diet and stress, as well as genetic factors. These changes can impair the ability of the gut microbiota to maintain good health and may allow the growth of potentially pathogenic bacteria (e.g., Clostridioides difficile), leading to production of metabolites that may cause a disease state in the host [61]. The relative abundance of bifidobacteria in faecal samples of normal-body-weight children was found to be higher than in overweight children of the same age bracket (7 years old). In contrast, Staphylococcus aureus levels were higher in the overweight children than in those with normal body weight [56]. In addition, a recent study reported an increased abundance of Firmicutes and a reduction in bifidobacteria in the gut microbiota of overweight and obese children [62]. Furthermore, it has been observed that children who became overweight/obese at age 10 years had significantly higher levels of Bacteroides fragilis in early infancy (3 to 6 weeks after birth) than those whose body weight remained normal [63]. These studies thus indicate that the microbial community of children may differ according to BMI, suggesting that the microbiota may have a part to play in weight gain, for example, through energy salvage. However, caution is required when considering causal links between the gut microbiota and obesity, as recent meta-analyses failed to find variations in the taxonomic microbial compositions of obese and lean adults, suggesting that microbiota differences observed in other studies could be related to factors such as diet [64][65][66]. Several other conditions, including eczema, asthma, inflammatory bowel disease (IBD) and type 1 diabetes, in infants and young children have been linked to differences in the gut microbiota. For instance, some studies show that infants with eczema have a significant reduction in relative abundance of Bifidobacterium, Blautia, Coprococcus, Eubacterium and Propionibacterium species [67] as well as a reduction in intestinal microbial population diversity [68][69]; although it is worth noting that in healthy infants, there is low microbiota diversity predominated by bifidobacteria. Moreover, an analysis of faecal microbiota of infants (1 to 11 months old) revealed that gut microbiota alteration promotes the disfunction of CD4+ T cells, which is linked to atopy in children [70]. Further, many studies have reported the gut microbiota to be altered in IBD [71][72][73][74], with an increase in Enterobacteriaceae being particularly prominent [75]. In addition, it has been found that children with prediabetes have higher levels of intestinal Bacteroidetes than healthy controls [76].

    The entry is from 10.3390/nu13082727


    1. United Nations Children’s Fund (UNICEF); World Health Organization; International Bank for Reconstruction and Development/The World Bank. Levels and Trends in Child Malnutrition: Key Findings of the 2018 Edition of the Joint Child Malnutrition Estimates; Licence: CC BY-NC-SA 3.0 IGO; World Health Organization: Geneva, Switzerland, 2018.
    2. UNICEF. Strategy for improved nutrition of children and women in developing countries. Indian J. Pediatr. 1991, 58, 13–24.
    3. Smith, M.I.; Yatsunenko, T.; Manary, M.J.; Trehan, I.; Mkakosya, R.; Cheng, J.; Kau, A.L.; Rich, S.S.; Concannon, P.; Mychaleckyj, J.C. Gut microbiomes of Malawian twin pairs discordant for kwashiorkor. Science 2013, 339, 548–554.
    4. Claus, S.P. Fighting undernutrition: Don’t forget the bugs. Cell Host Microbe 2013, 13, 239–240.
    5. Monira, S.; Shabnam, S.A.; Alam, N.H.; Endtz, H.P.; Cravioto, A.; Alam, M. 16S rRNA gene-targeted TTGE in determining diversity of gut microbiota during acute diarrhoea and convalescence. J. Health Popul. Nutr. 2012, 30, 250–256.
    6. Ma, C.; Wu, X.; Nawaz, M.; Li, J.; Yu, P.; Moore, J.E.; Xu, J. Molecular characterization of fecal microbiota in patients with viral diarrhea. Curr. Microbiol. 2011, 63, 259–266.
    7. Solano-Aguilar, G.; Fernandez, K.P.; Ets, H.; Molokin, A.; Vinyard, B.; Urban, J.F.; Gutierrez, M.F. Characterization of fecal microbiota of children with diarrhea in 2 locations in Colombia. J. Pediatr. Gastroenterol. Nutr. 2013, 56, 503–511.
    8. Irena, A.H.; Mwambazi, M.; Mulenga, V. Diarrhea is a major killer of children with severe acute malnutrition admitted to inpatient set-up in Lusaka, Zambia. Nutr. J. 2011, 10, 110.
    9. Talbert, A.; Thuo, N.; Karisa, J.; Chesaro, C.; Ohuma, E.; Ignas, J.; Berkley, J.A.; Toromo, C.; Atkinson, S.; Maitland, K. Diarrhoea complicating severe acute malnutrition in Kenyan children: A prospective descriptive study of risk factors and outcome. PLoS ONE 2012, 7, e38321.
    10. Pekmez, C.T.; Dragsted, L.O.; Brahe, L.K. Gut microbiota alterations and dietary modulation in childhood malnutrition—The role of short chain fatty acids. Clin. Nutr. 2018, 1–16.
    11. Sender, R.; Fuchs, S.; Milo, R. Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLoS Biol. 2016, 14, e1002533.
    12. May, G.A.; Reynolds, N.; Macfarlane, G.T. Effect of pH on an In Vitro Model of Gastric Microbiota in Enteral Nutrition Patients. Appl. Environ. Microbiol. 2005, 71, 4777.
    13. Cummings, J.H.; Macfarlane, G.T. The control and consequences of bacterial fermentation in the human colon. J. Appl. Bacteriol. 1991, 70, 443–459.
    14. Blaut, M. Relationship of prebiotics and food to intestinal microflora. Eur. J. Nutr. 2002, 41 (Suppl. 1), I/11–I/16.
    15. van den Elsen, L.W.J.; Poyntz, H.C.; Weyrich, L.S.; Young, W.; Forbes-Blom, E.E. Embracing the gut microbiota: The new frontier for inflammatory and infectious diseases. Clin. Transl. Immunol. 2017, 6, e125.
    16. Vinolo, M.A.; Rodrigues, H.G.; Nachbar, R.T.; Curi, R. Regulation of inflammation by short chain fatty acids. Nutrients 2011, 3, 858–876.
    17. Duca, F.A.; Lam, T.K.T. Gut microbiota, nutrient sensing and energy balance. Diabetes Obes. Metab. 2014, 16, 68–76.
    18. Blaut, M. Gut microbiota and energy balance: Role in obesity. Proc. Nutr. Soc. 2015, 74, 227–234.
    19. Bakker, G.J.; Zhao, J.; Herrema, H.; Nieuwdorp, M. Gut Microbiota and Energy Expenditure in Health and Obesity. J. Clin. Gastroenterol. 2015, 49, 227–234.
    20. Yatsunenko, T.; Rey, F.E.; Manary, M.J.; Trehan, I.; Dominguez-Bello, M.G.; Contreras, M.; Magris, M.; Hidalgo, G.; Baldassano, R.N.; Anokhin, A.P. Human gut microbiome viewed across age and geography. Nature 2012, 486, 222–227.
    21. LeBlanc, J.G.; Milani, C.; de Giori, G.S.; Sesma, F.; van Sinderen, D.; Ventura, M. Bacteria as vitamin suppliers to their host: A gut microbiota perspective. Curr. Opin. Biotechnol. 2013, 24, 160–168.
    22. Bauer, P.V.; Hamr, S.C.; Duca, F.A. Regulation of energy balance by a gut-brain axis and involvement of the gut microbiota. Cell. Mol. Life Sci. 2016, 73, 737–755.
    23. Martin, C.R.; Osadchiy, V.; Kalani, A.; Mayer, E.A. The Brain-Gut-Microbiome Axis. Cell. Mol. Gastroenterol. Hepatol. 2018, 6, 133–148.
    24. Bonaz, B.; Bazin, T.; Pellissier, S. The Vagus Nerve at the Interface of the Microbiota-Gut-Brain Axis. Front. Neurosci. 2018, 12, 49.
    25. Ringel-Kulka, T.; Kotch, J.B.; Jensen, E.T.; Savage, E.; Weber, D.J. Randomized, Double-Blind, Placebo-Controlled Study of Synbiotic Yogurt Effect on the Health of Children. J. Pediatr. 2015, 166, 1475–1481.e3.
    26. Umu, Ö.C.O.; Rudi, K.; Diep, D.B. Modulation of the gut microbiota by prebiotic fibres and bacteriocins. Microb. Ecol. Health Dis. 2017, 28, 1348886.
    27. Robertson, R.C.; Manges, A.R.; Finlay, B.B.; Prendergast, A.J. The Human Microbiome and Child Growth—First 1000 Days and Beyond. Trends Microbiol. 2019, 27, 131–147.
    28. Chu, D.M.; Ma, J.; Prince, A.L.; Antony, K.M.; Seferovic, M.D.; Aagaard, K.M. Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery. Nat. Med. 2017, 23, 314–326.
    29. Yassour, M.; Jason, E.; Hogstrom, L.J.; Arthur, T.D.; Tripathi, S.; Siljander, H.; Selvenius, J.; Oikarinen, S.; Hyöty, H.; Virtanen, S.M.; et al. Strain-Level Analysis of Mother-to-Child Bacterial Transmission during the First Few Months of Life. Cell Host Microbe 2018, 24, 146–154.e144.
    30. Duranti, S.; Milani, C.; Lugli, G.A.; Turroni, F.; Mancabelli, L.; Sanchez, B.; Ferrario, C.; Viappiani, A.; Mangifesta, M.; Mancino, W.; et al. Insights from genomes of representatives of the human gut commensal Bifidobacterium bifidum. Environ. Microbiol. 2015, 17, 2515–2531.
    31. Sela, D.A.; Chapman, J.; Adeuya, A.; Kim, J.H.; Chen, F.; Whitehead, T.R.; Lapidus, A.; Rokhsar, D.S.; Lebrilla, C.B.; German, J.B.; et al. The genome sequence of Bifidobacterium longum subsp. infantis reveals adaptations for milk utilization within the infant microbiome. Proc. Natl. Acad. Sci. USA 2008, 105, 18964.
    32. Ackerman, D.L.; Craft, K.M.; Townsend, S.D. Infant food applications of complex carbohydrates: Structure, synthesis, and function. Carbohydr. Res. 2017, 437, 16–27.
    33. Craft, K.M.; Townsend, S.D. The Human Milk Glycome as a Defense Against Infectious Diseases: Rationale, Challenges, and Opportunities. ACS Infect. Dis. 2018, 4, 77–83.
    34. Zhu, B.; Zheng, S.; Lin, K.; Xu, X.; Lv, L.; Zhao, Z.; Shao, J. Effects of Infant Formula Supplemented With Prebiotics and OPO on Infancy Fecal Microbiota: A Pilot Randomized Clinical Trial. Front. Cell. Infect. Microbiol. 2021, 11, 194.
    35. Gibson, G.R.; Hutkins, R.; Sanders, M.E.; Prescott, S.L.; Reimer, R.A.; Salminen, S.J.; Scott, K.; Stanton, C.; Swanson, K.S.; Cani, P.D.; et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat. Rev. Gastroenterol. Hepatol. 2017, 14, 491–502.
    36. Borewicz, K.; Suarez-Diez, M.; Hechler, C.; Beijers, R.; de Weerth, C.; Arts, I.; Penders, J.; Thijs, C.; Nauta, A.; Lindner, C.; et al. The effect of prebiotic fortified infant formulas on microbiota composition and dynamics in early life. Sci. Rep. 2019, 9, 2434.
    37. Knol, J.; Scholtens, P.; Kafka, C.; Steenbakkers, J.; Gro, S.; Helm, K.; Klarczyk, M.; Schöpfer, H.; Böckler, H.-M.; Wells, J. Colon Microflora in Infants Fed Formula with Galacto- and Fructo-Oligosaccharides: More Like Breast-Fed Infants. J. Pediatr. Gastroenterol. Nutr. 2005, 40, 36–42.
    38. Ninonuevo, M.R.; Bode, L. Infant Formula Oligosaccharides Opening the Gates (for Speculation): Commentary on the article by Barrat et al. on page 34. Pediatr. Res. 2008, 64, 8–10.
    39. Radke, M.; Picaud, J.C.; Loui, A.; Cambonie, G.; Faas, D.; Lafeber, H.N.; de Groot, N.; Pecquet, S.S.; Steenhout, P.G.; Hascoet, J.M. Starter formula enriched in prebiotics and probiotics ensures normal growth of infants and promotes gut health: A randomized clinical trial. Pediatr. Res. 2017, 81, 622–631.
    40. Moro, G.; Minoli, I.; Mosca, M.; Fanaro, S.; Jelinek, J.; Stahl, B.; Boehm, G. Dosage-Related Bifidogenic Effects of Galacto- and Fructooligosaccharides in Formula-Fed Term Infants. J. Pediatr. Gastroenterol. Nutr. 2002, 34, 291–295.
    41. Milani, C.; Duranti, S.; Bottacini, F.; Casey, E.; Turroni, F.; Mahony, J.; Belzer, C.; Delgado Palacio, S.; Arboleya Montes, S.; Mancabelli, L.; et al. The First Microbial Colonizers of the Human Gut: Composition, Activities, and Health Implications of the Infant Gut Microbiota. Microbiol. Mol. Biol. Rev. 2017, 81, e00036-17.
    42. Hill, C.; Guarner, F.; Reid, G.; Gibson, G.R.; Merenstein, D.J.; Pot, B.; Morelli, L.; Canani, R.B.; Flint, H.J.; Salminen, S.; et al. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat. Rev. Gastroenterol. Hepatol. 2014, 11, 506–514.
    43. Rijkers, G.T.; Bengmark, S.; Enck, P.; Haller, D.; Herz, U.; Kalliomaki, M.; Kudo, S.; Lenoir-Wijnkoop, I.; Mercenier, A.; Myllyluoma, E.; et al. Guidance for Substantiating the Evidence for Beneficial Effects of Probiotics: Current Status and Recommendations for Future Research. J. Nutr. 2010, 140, 671S–676S.
    44. Frese, S.A.; Hutton, A.A.; Contreras, L.N.; Shaw, C.A.; Palumbo, M.C.; Casaburi, G.; Xu, G.; Davis, J.C.C.; Lebrilla, C.B.; Henrick, B.M.; et al. Persistence of Supplemented Bifidobacterium longum subsp. infantis EVC001 in Breastfed Infants. mSphere 2017, 2, e00501-17.
    45. Guarner, F.; Khan, A.G.; Garisch, J.; Eliakim, R.; Gangl, A.; Thomson, A.; Krabshuis, J.; Lemair, T.; Kaufmann, P.; de Paula, J.A.; et al. World Gastroenterology Organisation Global Guidelines: Probiotics and prebiotics October 2011. J. Clin. Gastroenterol. 2012, 46, 468–481.
    46. Sung, V.; D’Amico, F.; Cabana, M.D.; Chau, K.; Koren, G.; Savino, F.; Szajewska, H.; Deshpande, G.; Dupont, C.; Indrio, F.; et al. Lactobacillus reuteri to Treat Infant Colic: A Meta-analysis. Pediatrics 2018, 141, e20171811.
    47. McFarland, L.V. Deciphering meta-analytic results: A mini-review of probiotics for the prevention of paediatric antibiotic-associated diarrhoea and Clostridium difficile infections. Benef. Microbes 2015, 6, 189–194.
    48. McFarland, L.V. Meta-Analysis of Probiotics for the Prevention of Antibiotic Associated Diarrhea and the Treatment of Clostridium difficile Disease. Am. J. Gastroenterol. 2006, 101, 812–822.
    49. Schnadower, D.; Tarr, P.I.; Casper, T.C.; Gorelick, M.H.; Dean, J.M.; O’Connell, K.J.; Mahajan, P.; Levine, A.C.; Bhatt, S.R.; Roskind, C.G.; et al. Lactobacillus rhamnosus GG versus Placebo for Acute Gastroenteritis in Children. N. Engl. J. Med. 2018, 379, 2002–2014.
    50. Nixon, A.F.; Cunningham, S.J.; Cohen, H.W.; Crain, E.F. The effect of Lactobacillus GG on acute diarrheal illness in the pediatric emergency department. Pediatr. Emerg. Care 2012, 28, 1048–1051.
    51. Collinson, S.; Deans, A.; Padua-Zamora, A.; Gregorio, G.V.; Li, C.; Dans, L.F.; Allen, S.J. Probiotics for treating acute infectious diarrhoea. Cochrane Database Syst. Rev. 2020.
    52. Mangiola, F.; Ianiro, G.; Franceschi, F.; Fagiuoli, S.; Gasbarrini, G.; Gasbarrini, A. Gut microbiota in autism and mood disorders. World J. Gastroenterol. 2016, 22, 361–368.
    53. Ridaura, V.K.; Faith, J.J.; Rey, F.E.; Cheng, J.; Duncan, A.E.; Kau, A.L.; Griffin, N.W.; Lombard, V.; Henrissat, B.; Bain, J.R.; et al. Gut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice. Science 2013, 341, 1241214.
    54. Hsiao, E.Y.; McBride, S.W.; Hsien, S.; Sharon, G.; Hyde, E.R.; McCue, T.; Codelli, J.A.; Chow, J.; Reisman, S.E.; Petrosino, J.F.; et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 2013, 155, 1451–1463.
    55. Scher, J.U.; Ubeda, C.; Artacho, A.; Attur, M.; Isaac, S.; Reddy, S.M.; Marmon, S.; Neimann, A.; Brusca, S.; Patel, T.; et al. Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease. Arthritis Rheumatol. 2015, 67, 128–139.
    56. Kalliomaki, M.; Collado, M.C.; Salminen, S.; Isolauri, E. Early differences in fecal microbiota composition in children may predict overweight. Am. J. Clin. Nutr. 2008, 87, 534–538.
    57. Gevers, D.; Kugathasan, S.; Denson, L.A.; Vázquez-Baeza, Y.; Van Treuren, W.; Ren, B.; Schwager, E.; Knights, D.; Song, S.J.; Yassour, M.; et al. The treatment-naive microbiome in new-onset Crohn’s disease. Cell Host Microbe 2014, 15, 382–392.
    58. Matsumoto, S.; Watanabe, N.; Imaoka, A.; Okabe, Y. Preventive effects of Bifidobacterium- and Lactobacillus-fermented milk on the development of inflammatory bowel disease in senescence-accelerated mouse P1/Yit strain mice. Digestion 2001, 64, 92–99.
    59. Mardini, H.E.; Grigorian, A.Y. Probiotic mix VSL#3 is effective adjunctive therapy for mild to moderately active ulcerative colitis: A meta-analysis. Inflamm. Bowel Dis. 2014, 20, 1562–1567.
    60. Ishikawa, H.; Matsumoto, S.; Ohashi, Y.; Imaoka, A.; Setoyama, H.; Umesaki, Y.; Tanaka, R.; Otani, T. Beneficial Effects of Probiotic Bifidobacterium and Galacto-Oligosaccharide in Patients with Ulcerative Colitis: A Randomized Controlled Study. Digestion 2011, 84, 128–133.
    61. Genth, H.; Huelsenbeck, J.; Hartmann, B.; Hofmann, F.; Just, I.; Gerhard, R. Cellular stability of Rho-GTPases glucosylated by Clostridium difficile toxin B. FEBS Lett. 2006, 580, 3565–3569.
    62. Da Silva, C.C.; Monteil, M.A.; Davis, E.M. Overweight and Obesity in Children Are Associated with an Abundance of Firmicutes and Reduction of Bifidobacterium in Their Gastrointestinal Microbiota. Child. Obes. 2020, 16, 204–210.
    63. Scheepers, L.E.J.M.; Penders, J.; Mbakwa, C.A.; Thijs, C.; Mommers, M.; Arts, I.C.W. The intestinal microbiota composition and weight development in children: The KOALA Birth Cohort Study. Int. J. Obes. 2015, 39, 16–25.
    64. Walters, W.A.; Xu, Z.; Knight, R. Meta-analyses of human gut microbes associated with obesity and IBD. FEBS Lett. 2014, 588, 4223–4233.
    65. Sze, M.A.; Schloss, P.D. Looking for a Signal in the Noise: Revisiting Obesity and the Microbiome. mBio 2016, 7, e01018-16.
    66. Finucane, M.M.; Sharpton, T.J.; Laurent, T.J.; Pollard, K.S. A Taxonomic Signature of Obesity in the Microbiome? Getting to the Guts of the Matter. PLoS ONE 2014, 9, e84689.
    67. Reddel, S.; Del Chierico, F.; Quagliariello, A.; Giancristoforo, S.; Vernocchi, P.; Russo, A.; Fiocchi, A.; Rossi, P.; Putignani, L.; El Hachem, M. Gut microbiota profile in children affected by atopic dermatitis and evaluation of intestinal persistence of a probiotic mixture. Sci. Rep. 2019, 9, 4996.
    68. Wang, M.; Karlsson, C.; Olsson, C.; Adlerberth, I.; Wold, A.E.; Strachan, D.P.; Martricardi, P.M.; Åberg, N.; Perkin, M.R.; Tripodi, S.; et al. Reduced diversity in the early fecal microbiota of infants with atopic eczema. J. Allergy Clin. Immunol. 2008, 121, 129–134.
    69. Forno, E.; Onderdonk, A.B.; McCracken, J.; Litonjua, A.A.; Laskey, D.; Delaney, M.L.; DuBois, A.M.; Gold, D.R.; Ryan, L.M.; Weiss, S.T.; et al. Diversity of the gut microbiota and eczema in early life. Clin. Mol. Allergy 2008, 6, 11.
    70. Fujimura, K.E.; Sitarik, A.R.; Havstad, S.; Lin, D.L.; Levan, S.; Fadrosh, D.; Panzer, A.R.; LaMere, B.; Rackaityte, E.; Lukacs, N.W.; et al. Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation. Nat. Med. 2016, 22, 1187–1191.
    71. Casén, C.; Vebø, H.C.; Sekelja, M.; Hegge, F.T.; Karlsson, M.K.; Ciemniejewska, E.; Dzankovic, S.; Frøyland, C.; Nestestog, R.; Engstrand, L.; et al. Deviations in human gut microbiota: A novel diagnostic test for determining dysbiosis in patients with IBS or IBD. Aliment. Pharmacol. Ther. 2015, 42, 71–83.
    72. Walker, A.W.; Sanderson, J.D.; Churcher, C.; Parkes, G.C.; Hudspith, B.N.; Rayment, N.; Brostoff, J.; Parkhill, J.; Dougan, G.; Petrovska, L. High-throughput clone library analysis of the mucosa-associated microbiota reveals dysbiosis and differences between inflamed and non-inflamed regions of the intestine in inflammatory bowel disease. BMC Microbiol. 2011, 11, 7.
    73. Marchesi, J.R.; Holmes, E.; Khan, F.; Kochhar, S.; Scanlan, P.; Shanahan, F.; Wilson, I.D.; Wang, Y. Rapid and Noninvasive Metabonomic Characterization of Inflammatory Bowel Disease. J. Proteome Res. 2007, 6, 546–551.
    74. Zhang, M.; Liu, B.; Zhang, Y.; Wei, H.; Lei, Y.; Zhao, L. Structural shifts of mucosa-associated lactobacilli and Clostridium leptum subgroup in patients with ulcerative colitis. J. Clin. Microbiol. 2007, 45, 496–500.
    75. Hedin, C.R.; McCarthy, N.E.; Louis, P.; Farquharson, F.M.; McCartney, S.; Taylor, K.; Prescott, N.J.; Murrells, T.; Stagg, A.J.; Whelan, K.; et al. Altered intestinal microbiota and blood T cell phenotype are shared by patients with Crohn’s disease and their unaffected siblings. Gut 2014, 63, 1578–1586.
    76. Dunne, J.L.; Triplett, E.W.; Gevers, D.; Xavier, R.; Insel, R.; Danska, J.; Atkinson, M.A. The intestinal microbiome in type 1 diabetes. Clin. Exp. Immunol. 2014, 177, 30–37.