JPGN Journal Club: March 2025
Are we all recovered from January, of all months the most Monday-ish? Experience might teach us how to cope with, dear Lord, the first of three more months of winter. But no. Instead, the older one becomes, the more burdensome January is.
Well, take heart: In the wonderland of JPGN Journal Club, led by Dr. Jake Mann, as the accompanying podcast is recorded, we’re deep into February. Listeners, keep on keeping on! Spring WILL arrive – just not soon enough.
Despite this horrid winter, ESPGHAN continues to work tirelessly for you. Visit https://www.espghan.org/knowledge-center – on III.05 there’s the GI Immunology Master Class: From pathogenesis to clinical management of EGID, coeliac disease, and IBD; on IV.02–04, there’s the Nutritional Assessment in Artificially Fed Children with Chronic Intestinal Disorders meeting; and, of course, the Helsinki annual meeting, V.14–17, is coming up. The calendar contains a clutch of further opportunities, beginning in early September. Not listed through ESPGHAN, but surely of interest to some in this podcast’s audience, will be the Congress on Pediatric Neurogastroenterology and Motility (Amsterdam, IX.11–13; www.pnm2025.nl).
Jake’s choices for discussion today: From J Pediatr Gastroenterol Nutr, by Mallhi et al., writing from five USA institutions, “The change of alanine aminotransferase distributions among US youths, NHANES 1988–2020”, and from Nat Commun, by Portlock et al., with co-authors at institutions that circle the globe, “Interconnected pathways link faecal microbiota plasma lipids and brain activity to childhood malnutrition-related cognition.”
The JPGN article prompts two queries: What is NHANES? And why should one care about serum alanine aminotransferase (ALT) activity values (15,000 determinations) over 30 years in USA adolescents?
Easy answer first: NHANES is the National Health and Nutrition Examination Survey, which in USA residents collects demographic, socio-economic, dietary, and health-related data together with findings on physical examination and results of clinical-laboratory studies.
Tougher answer now: ALT values have been posited to track metabolic-dysfunction-associated steatotic liver disease (MASLD). Might population-wide ALT-value shifts allow assessment of effects of public-health interventions (reduction in consumption of ethanol/high-fructose sweeteners among adolescents)? Might they indicate sub-populations in whom further interventions are needed if MASLD incidence is to be reduced?
Using NHANES cohorts defined by age and by body-weight status (obese, overweight, normal, underweight), the authors identified across-the-board rises in ALT values when obesity increased among teenagers – and across-the-board falls in ALT values after access to ethanol and high-fructose sweeteners was restricted. Whilst ALT values fell overall, however, the incidence of MASLD did not. As always, then, more work is to be done if the burden of MASLD is to be reduced.
Malnutrition in childhood is, in survivors, associated with subnormal intelligence. What are the links between these two phenomena? The article from Nat Commun describes attempts to identify correlations among the enterobiome, stool composition, plasma lipid profiles, and evidence for impaired brain growth, development, and function, as assessed in two cohorts of Bangladeshi infants aged 11–13 months: 75 well-nourished (WN) and 159 with moderate acute malnutrition (MAM).
The enterobiome of infants with MAM was less diverse than that of WN infants, with an increased proportion of oral flora (although stool composition did not differ significantly between the cohorts). Among 792 plasma lipids assessed, differences between the cohorts were seen in 40 – some higher in MAM infants, some lower. Circulating odd-chain fatty acids and ceramides, in particular, were depleted in MAM.
Resting electroencephalography found decreased temporofrontal beta (12–30 Hz) and gamma (30–45 Hz) band activity, associated with concentration and alertness, in infants with MAM, who also, on behavioural assessment, lagged behind WN infants.
Network analyses found that Bacteroides fragilis abundance, in particular, was decreased in MAM. B. fragilis synthesizes several lipids important in nervous-system growth and development, and these lipids were depleted in MAM infants.
A mechanistic link remains to be tested in animal models, but the association is suggestive. Whether early intervention to prevent MAM – by provision of sufficient calories, perhaps – could generate changes in the enterobiome and, possibly in consequence, restoration of normal plasma lipid profiles, increases in electroencephalographic band activity, and regaining of age-appropriate neurodevelopmental milestones remains to be seen.
Literature
Mallhi AK et al. The change of alanine aminotransferase distributions among US youths, NHANES 1988–2020. J Pediatr Gastroenterol Nutr. 2025 Jan 13. PMID: 39803838 DOI: 10.1002/jpn3.12460
Portlock T et al. Interconnected pathways link faecal microbiota plasma lipids and brain activity to childhood malnutrition-related cognition. Nat Commun. 2025 Jan; 816(1):473. PMID: 39773949 PMCID: PMC11707170 DOI: 10.1038/s41467-024-55798-3