Intestinal Mucosal Permeability of Severely Underweight and Nonmalnourished Bangladeshi Children and Effects of Nutritional Rehabilitation

Hossain, Iqbal; Nahar, Baitun; Hamadani, Jena D.; Ahmed, Tahmeed; Roy, Anjan Kumar; Brown, Kenneth H.

doi:10.1097/mpg.0b013e3181eb3128

Cited by 38 publications

(49 citation statements)

References 31 publications

(54 reference statements)

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“…However, the mucosal atrophy and functional changes did not only occur in malnourished children. Although sometimes found to be most severe in malnourished children [33] [35]–[36] [46]–[47], similar abnormalities were present in apparently well-nourished children from the same environment [38]–[40] [43] [50], and frequently persisted after nutritional recovery [34] [37] [51].…”

Section: Resultsmentioning

confidence: 95%

The Immune System in Children with Malnutrition—A Systematic Review

et al. 2014

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BackgroundMalnourished children have increased risk of dying, with most deaths caused by infectious diseases. One mechanism behind this may be impaired immune function. However, this immune deficiency of malnutrition has not previously been systematically reviewed.ObjectivesTo review the scientific literature about immune function in children with malnutrition.MethodsA systematic literature search was done in PubMed, and additional articles identified in reference lists and by correspondence with experts in the field. The inclusion criteria were studies investigating immune parameters in children aged 1–60 months, in relation to malnutrition, defined as wasting, underweight, stunting, or oedematous malnutrition.ResultsThe literature search yielded 3402 articles, of which 245 met the inclusion criteria. Most were published between 1970 and 1990, and only 33 after 2003. Malnutrition is associated with impaired gut-barrier function, reduced exocrine secretion of protective substances, and low levels of plasma complement. Lymphatic tissue, particularly the thymus, undergoes atrophy, and delayed-type hypersensitivity responses are reduced. Levels of antibodies produced after vaccination are reduced in severely malnourished children, but intact in moderate malnutrition. Cytokine patterns are skewed towards a Th2-response. Other immune parameters seem intact or elevated: leukocyte and lymphocyte counts are unaffected, and levels of immunoglobulins, particularly immunoglobulin A, are high. The acute phase response appears intact, and sometimes present in the absence of clinical infection. Limitations to the studies include their observational and often cross-sectional design and frequent confounding by infections in the children studied.ConclusionThe immunological alterations associated with malnutrition in children may contribute to increased mortality. However, the underlying mechanisms are still inadequately understood, as well as why different types of malnutrition are associated with different immunological alterations. Better designed prospective studies are needed, based on current understanding of immunology and with state-of-the-art methods.

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Section: Resultsmentioning

confidence: 95%

The Immune System in Children with Malnutrition—A Systematic Review

et al. 2014

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“…This amino acid is an important component of mucin-2 that is secreted by goblet cells to maintain the intestinal barrier (31). The lower threonine in those with kwashiorkor may reflect a more severe barrier dysfunction, which is known to be severely compromised in children with SAM (32). …”

Section: Discussionmentioning

confidence: 99%

Metabolomic Changes in Serum of Children with Different Clinical Diagnoses of Malnutrition

Giovanni¹,

Bourdon²,

Wang³

et al. 2016

The Journal of Nutrition

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Background: Mortality in children with severe acute malnutrition (SAM) remains high despite standardized rehabilitation protocols. Two forms of SAM are classically distinguished: kwashiorkor and marasmus. Children with kwashiorkor have nutritional edema and metabolic disturbances, including hypoalbuminemia and hepatic steatosis, whereas marasmus is characterized by severe wasting. The metabolic changes underlying these phenotypes have been poorly characterized, and whether homeostasis is achieved during hospital stay is unclear.Objectives: We aimed to characterize metabolic differences between children with marasmus and kwashiorkor at hospital admission and after clinical stabilization and to compare them with stunted and nonstunted community controls.Methods: We studied children aged 9–59 mo from Malawi who were hospitalized with SAM (n = 40; 21 with kwashiorkor and 19 with marasmus) or living in the community (n = 157; 78 stunted and 79 nonstunted). Serum from patients with SAM was obtained at hospital admission and 3 d after nutritional stabilization and from community controls. With the use of targeted metabolomics, 141 metabolites, including amino acids, biogenic amines, acylcarnitines, sphingomyelins, and phosphatidylcholines, were measured.Results: At admission, most metabolites (128 of 141; 91%) were lower in children with kwashiorkor than in those with marasmus, with significant differences in several amino acids and biogenic amines, including those of the kynurenine-tryptophan pathway. Several phosphatidylcholines and some acylcarnitines also differed. Patients with SAM had profiles that were profoundly different from those of stunted and nonstunted controls, even after clinical stabilization. Amino acids and biogenic amines generally improved with nutritional rehabilitation, but most sphingomyelins and phosphatidylcholines did not.Conclusions: Children with kwashiorkor were metabolically distinct from those with marasmus, and were more prone to severe metabolic disruptions. Children with SAM showed metabolic profiles that were profoundly different from stunted and nonstunted controls, even after clinical stabilization. Therefore, metabolic recovery in children with SAM likely extends beyond discharge, which may explain the poor long-term outcomes in these children. This trial was registered at isrctn.org as ISRCTN13916953.

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“…It is further hypothesized to contribute to a reciprocal cycle of childhood malnutrition and infection and to mitigate the efficacy of oral vaccines against gut or gut-acquired pathogens (32,39,47,61). The typical pathological features of malnutrition enteropathy include small bowel villous atrophy, crypt hyperplasia, and lamina propria lymphoplasmacytic inflammation; however, the pathogenesis of these changes is only partially understood, as are optimal approaches to prevention and therapy (6,24,28,34,39,43,45,60,66).…”

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confidence: 98%

Alanyl-glutamine promotes intestinal epithelial cell homeostasis in vitro and in a murine model of weanling undernutrition

Ueno

Oriá²,

Maier

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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Alanyl-glutamine (Ala-Gln) has recently been shown to enhance catch-up growth and gut integrity in undernourished children from Northeast Brazil. We hypothesized that the intestinal epithelial effects of Ala-Gln in malnourished weanling mice and mouse small intestinal epithelial (MSIE) cells would include modulation of barrier function, proliferation, and apoptosis. Dams of 10-day-old suckling C57BL/6 pups were randomized to a standard diet or an isocaloric Northeast Brazil "regional basic diet," moderately deficient in protein, fat, and minerals. Upon weaning to their dam's diet on day of life 21, pups were randomized to Ala-Gln solution or water. At 6 wk of age, mice were killed, and jejunal tissue was collected for morphology, immunohistochemistry, and Ussing chamber analysis of transmucosal resistance and permeability. Proliferation of MSIE cells in the presence or absence of Ala-Gln was measured by MTS and bromodeoxyuridine assays. MSIE apoptosis was assessed by annexin and 7-amino-actinomycin D staining. Pups of regional basic diet-fed dams exhibited failure to thrive. Jejunal specimens from undernourished weanlings showed decreased villous height and crypt depth, decreased transmucosal resistance, increased permeability to FITC-dextran, increased claudin-3 expression, and decreased epithelial proliferation and increased epithelial apoptosis (as measured by bromodeoxyuridine and cleaved caspase-3 staining, respectively). Undernourished weanlings supplemented with Ala-Gln showed improvements in weight velocity, villous height, crypt depth, transmucosal resistance, and epithelial proliferation/apoptosis compared with unsupplemented controls. Similarly, Ala-Gln increased proliferation and reduced apoptosis in MSIE cells. In summary, Ala-Gln promotes intestinal epithelial homeostasis in a mouse model of malnutrition-associated enteropathy, mimicking key features of the human disease.

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Intestinal Mucosal Permeability of Severely Underweight and Nonmalnourished Bangladeshi Children and Effects of Nutritional Rehabilitation

Cited by 38 publications

References 31 publications

The Immune System in Children with Malnutrition—A Systematic Review

The Immune System in Children with Malnutrition—A Systematic Review

Metabolomic Changes in Serum of Children with Different Clinical Diagnoses of Malnutrition

Alanyl-glutamine promotes intestinal epithelial cell homeostasis in vitro and in a murine model of weanling undernutrition

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