Intestinal microbiome changes in an infant with right atrial isomerism and recurrent necrotizing enterocolitis: A case report and review of literature.

BACKGROUND: Necrotizing enterocolitis (NEC) is a multifactorial disease that predominantly affects premature neonates. Intestinal dysbiosis plays a critical role in NEC pathogenesis in premature neonates. The main risk factor for NEC in term infants is mesenteric hypoperfusion associated with ductal-dependent congenital heart disease (CHD) that eventually leads to intestinal ischemia. The incidence of NEC in neonates with critical CHD is 6.8%-13%. However, the role of the intestinal microbiome in NEC pathogenesis in infants with ductal-dependent CHD remains unclear. CASE SUMMARY: A male term neonate with right atrial isomerism underwent modified Blalock-Taussig shunt placement on the 14th day of life and had persistent mesenteric hypoperfusion after surgery. The patient had episodes of NEC stage IIA on the 1st and 28th days after cardiac surgery. Fecal microbial composition was analyzed before and after cardiac surgery by sequencing region V4 of the 16S rRNA gene. Before surgery, species belonging to genera Veillonella and Clostridia and class Gammaproteobacteria were detected, Bifidobacteriaceae showed a low abundance. The first NEC episode was associated with postoperative hemodynamic instability, intestinal ischemia-reperfusion injury during cardiopulmonary bypass, and a high abundance of Clostridium paraputrificum (Clostridium sensu stricto I) (56.1%). Antibacterial therapy after the first NEC episode resulted in increased abundance of Gammaproteobacteria, decreased abundance of Firmicutes, and low alpha diversity. These changes in the microbial composition promoted the growth of Clostridium sensu stricto I (72.0%) before the second NEC episode. CONCLUSION: A high abundance of Clostridium sensu stricto I and mesenteric hypoperfusion may have contributed to NEC in the present case.

NMDA and GABA receptor presence in rat heart mitochondria.

The purpose of this study is to demonstrate the presence of three more receptors in mitochondria. Two N-methyl-d-aspartate receptor (NMDAR) subunits (NR1 and NR2B) are found by protein immunoblot and immunogold labeling in mitochondria fraction isolated from rat heart. These data allow supposing NMDAR presence and functioning in the inner mitochondrial membrane. There are no signs of receptor presence obtained in heart tissue lysate, that indicates the receptor localization exactly in mitochondria. The possible receptor functions discussed are its participation in calcium transport and in excitation-metabolism coupling. Besides, preliminary evidence is obtained of GABAA and GABAB receptors presence in heart mitochondria. One can surmise their role in metabolism regulation and their possible co-operation with NMDAR just as in the nervous system.

On the regulative role of the glutamate receptor in mitochondria.

The purpose of this work was to study the regulative role of the glutamate receptor found earlier in the brain mitochondria. In the present work a glutamate-dependent signaling system with similar features was detected in mitochondria of the heart. The glutamate-dependent signaling system in the heart mitochondria was shown to be suppressed by γ-aminobutyric acid (GABA). The GABA receptor presence in the heart mitochondria was shown by golding with the use of antibodies to α- and ß-subunits of the receptor. The activity of glutamate receptor was assessed according to the rate of synthesis of hydrogen peroxide. The glutamate receptor in mitochondria could be activated only under conditions of hypoxic stress, which in model experiments was imitated by blocking Complex I by rotenone or fatty acids. The glutamate signal in mitochondria was shown to be calcium- and potential-dependent and the activation of the glutamate cascade was shown to be accompanied by production of hydrogen peroxide. It was discovered that H2O2 synthesis involves two complexes of the mitochondrial electron transfer system - succinate dehydrogenase (SDH) and fatty acid dehydrogenase (ETF:QO). Thus, functions of the glutamate signaling system are associated with the system of respiration-glycolysis switching (the Pasteur-Crabtree) under conditions of hypoxia.