Stunted children display ectopic small intestinal colonization by oral bacteria, which cause lipid malabsorption in experimental models.

Environmental enteric dysfunction (EED) is an inflammatory syndrome postulated to contribute to stunted child growth and to be associated with intestinal dysbiosis and nutrient malabsorption. However, the small intestinal contributions to EED remain poorly understood. This study aimed to assess changes in the proximal and distal intestinal microbiota in the context of stunting and EED and to test for a causal role of these bacterial isolates in the underlying pathophysiology. We performed a cross-sectional study in two African countries recruiting roughly 1,000 children aged 2 to 5 years and assessed the microbiota in the stomach, duodenum, and feces. Upper gastrointestinal samples were obtained from stunted children and stratified according to stunting severity. Fecal samples were collected. We then investigated the role of clinical isolates in EED pathophysiology using tissue culture and animal models. We find that small intestinal bacterial overgrowth (SIBO) is extremely common (>80%) in stunted children. SIBO is frequently characterized by an overgrowth of oral bacteria, leading to increased permeability and inflammation and to replacement of classical small intestinal strains. These duodenal bacterial isolates decrease lipid absorption in both cultured enterocytes and mice, providing a mechanism by which they may exacerbate EED and stunting. Further, we find a specific fecal signature associated with the EED markers fecal calprotectin and alpha-antitrypsin. Our study shows a causal implication of ectopic colonization of oral bacterial isolated from the small intestine in nutrient malabsorption and gut leakiness in vitro. These findings have important therapeutic implications for modulating the microbiota through microbiota-targeted interventions.

Stunted childhood growth is associated with decompartmentalization of the gastrointestinal tract and overgrowth of oropharyngeal taxa.

Linear growth delay (stunting) affects roughly 155 million children under the age of 5 years worldwide. Treatment has been limited by a lack of understanding of the underlying pathophysiological mechanisms. Stunting is most likely associated with changes in the microbial community of the small intestine, a compartment vital for digestion and nutrient absorption. Efforts to better understand the pathophysiology have been hampered by difficulty of access to small intestinal fluids. Here, we describe the microbial community found in the upper gastrointestinal tract of stunted children aged 2-5 y living in sub-Saharan Africa. We studied 46 duodenal and 57 gastric samples from stunted children, as well as 404 fecal samples from stunted and nonstunted children living in Bangui, Central African Republic, and in Antananarivo, Madagascar, using 16S Illumina Amplicon sequencing and semiquantitative culture methods. The vast majority of the stunted children showed small intestinal bacterial overgrowth dominated by bacteria that normally reside in the oropharyngeal cavity. There was an overrepresentation of oral bacteria in fecal samples of stunted children, opening the way for developing noninvasive diagnostic markers. In addition, Escherichia coli/Shigella sp. and Campylobacter sp. were found to be more prevalent in stunted children, while Clostridia, well-known butyrate producers, were reduced. Our data suggest that stunting is associated with a microbiome "decompartmentalization" of the gastrointestinal tract characterized by an increased presence of oropharyngeal bacteria from the stomach to the colon, hence challenging the current view of stunting arising solely as a consequence of small intestine overstimulation through recurrent infections by enteric pathogens.

First cases of Burkholderia cenocepacia IIIA neonatal sepsis in Central African Republic.

Bacteria of the Burkholderia cepacia complex cause frequent infections in immunocompromised and hospitalized patients, with a significant mortality rate. Phenotypic identification of those bacteria is difficult and therefore rarely reported from developing countries. This study presents the first ever reported case series of Burkholderia cenocepacia neonatal sepsis in Central African Republic. It demonstrates the superiority of molecular methods to accurately identify B. cenocepacia IIIA species compared to the phenotypic methods.

Burkholderia cepacia meningitis in the Central African Republic.

Burkholderia cepacia causes frequent infections in immunocompromised and hospitalized patients, with a significant mortality rate. This bacterial species has also been associated with epidemic outbreaks due to contamination of antiseptic solutions and parenteral and nebulized medications. In 2016, in the town of Bongonon in the north of the Central African Republic (CAR), a three-year-old boy with febrile meningeal syndrome (fever, neck stiffness and altered general condition) was admitted for a medical consultation provided by the nongovernmental organization MSF-Spain. On 20 March 2016, a sample of the boy's cerebrospinal fluid was sent to the Bacteriology Laboratory of the Pasteur Institute of Bangui for analysis. Conventional bacteriology showed that the isolate was a Gram-negative bacillus, which was identified as B. cepacia by using API 20 NE, with 99.9%confidence. In addition, the strain presented an acquired resistance to ticarcillin-clavulanate, ceftazidime and imipenem but remained susceptible to cotrimoxazole. As B. cepacia had never previously been isolated from cerebrospinal fluid in Africa, we chose to identify the strain by 16S rRNA gene sequencing. The molecular data showed that the isolate belonged to B. cepacia group. This is the first report of a case of meningitis caused by B. cepacia in CAR and developing countries.