ESPE Abstracts (2022) 95 P1-483

ESPE2022 Poster Category 1 Fat, Metabolism and Obesity (73 abstracts)

The ecology of the microbiome in children with congenital generalized lipodystrophy type 4 (CGL4) is quickly modified after metreleptin treatment

Valentina Mancioppi 1 , Tommaso Daffara 2 , Marina Caputo 2 , Simonetta Bellone 1 , Nadia Massa 3 , Alice Caramaschi 3,4 , Flavio Mignone 3,5 , Martina Romanisio 2 , Ivana Rabbone 1 , Mara Giordano 6 , Gianluca Aimaretti 2,6 , Elisa Bona 3,4 & Flavia Prodam 2,6

1SCDU Pediatrics, Department of Health Sciences, Novara, Italy; 2Endocrinology Unit, Department of Translational Medicine, Novara, Italy; 3Department of Sciences and Technological Innovation, Alessandria, Italy; 4Department for Sustainable Development and Ecological Transition, Vercelli, Italy; 5SmartSeq s.r.l., spin-off of the Università del Piemonte Orientale, Novara, Italy; 6Department of Health Sciences, Novara, Italy

Introduction: Lipodystrophy syndromes are characterized by a progressive metabolic impairment secondary to adipose tissue dysfunction and genetic background. The role of microbiota is still uninvestigated.

Objective: Evaluate the gut microbiome ecology in relation to dietary and clinical parameters in two infant siblings with congenital generalized lipodystrophy type 4 (CGL4) before and after treatment with recombinant leptin.

Methods: Two siblings (male, 5.5 years; female 2.5 years) with CGL4 caused by a new homozygous PTRF mutation (NM_012232 eson1:c T21A:p. Y7X) were identified and followed after the starting of leptin treatment. We collected auxological, metabolic, nutritional parameters, and stool samples at baseline and every 3 months. Two baseline stool samples were pooled. DNA was extracted directly from 0.25 g of stool using the QIAamp PowerFecal Pro DNA Kit. DNA was amplified with primers for the V3 and V6 regions of 16S rDNA tagged with Multiplex Identifier sequences using Microbiota Solution B Kit optimized for Illumina Miseq sequencing. Raw FastQ sequences were analyzed using MicrobAT Software. Statistical analyses were performed using MicrobiomeAnalyst and R software.

Results: At baseline, reduced subcutaneous fat, muscular hypertrophy, distinct facial features, myopathy, atlantoaxial instability were observed. Stature and BMI were normal. Blood tests showed elevated CK, mildly elevated levels of liver enzymes and triglycerides, low leptin and adiponectin levels. Fasting glucose and HbA1c were normal; HOMA-IR was mildly elevated in the female, and continuous glucose monitoring often detected glucose higher than 180 mg/dl after meals in male. They were hyperphagic, mainly for foods rich in fats and sugars. The 2 subjects showed a Bacteroides enterotype (F/M): 46%/44% Bacteroidetes, 49%/42% Firmicutes, 0.02%/0.04 other Bacteria, 3.2%/1.9% Actinobacteria, 0.7%/0.4% Proteobacteria; 0%/11%Verrucomicrobia. Treatment with metreleptin was started at standard dose according to age and weight. Metabolic parameters and hyperphagia improved, and they were more adherent to dietary indications. The male subject lost 0.8 Kg after 3 months, female weight was stable. We present microbiome ecology after 3-month treatment, before starting also medium-chain triglyceride oil formulas. Alfa-diversity increased in both children. Ecology was modified (P<0.06) with a reproducible signature with decreased and increased relative abundance of species linked to metabolic homeostasis.

Discussion: These preliminary results highlight as dietary adherence and leptin treatment were soon followed by improvements in metabolic alterations and changes in microbiome ecology. Whether microbiota composition and function have a role in the lipodystrophy phenotype needs further investigation. Our preliminary data should be validated in a wide cohort.

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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