Souleymane Brah

Increased Gut Redox and Depletion of Anaerobic and Methanogenic Prokaryotes in Severe Acute Malnutrition

Severe acute malnutrition (SAM) is associated with inadequate diet, low levels of plasma antioxidants and gut microbiota alterations. The link between gut redox and microbial alterations, however, remains unexplored. By sequencing the gut microbiomes of 79 children of varying nutritional status from three centers in Senegal and Niger, we found a dramatic depletion of obligate anaerobes in malnutrition. This was confirmed in an individual patient data meta-analysis including 107 cases and 77 controls from 5 different African and Asian countries. Specifically, several species of the Bacteroidaceae, Eubacteriaceae, Lachnospiraceae and Ruminococceae families were consistently depleted while Enterococcus faecalis, Escherichia coli and Staphylococcus aureus were consistently enriched. Further analyses on our samples revealed increased fecal redox potential, decreased total bacterial number and dramatic Methanobrevibacter smithii depletion. Indeed, M. smithii was detected in more than half of the controls but in none of the cases. No causality was demonstrated but, based on our results, we propose a unifying theory linking microbiota specificity, lacking anaerobes and archaea, to low antioxidant nutrients, and lower food conversion.

Gut Bacteria Missing in Severe Acute Malnutrition, Can We Identify Potential Probiotics by Culturomics?

Severe acute malnutrition is the world-leading cause of children under-fives death. Recent metagenomics studies have established a link between gut microbiota and severe acute malnutrition, describing an immaturity with a striking depletion in oxygen-sensitive prokaryotes. Amoxicillin and therapeutic diet cure most of the children with severe acute malnutrition but an irreversible disruption of the gut microbiota is suspected in the refractory and most severe cases. In these cases, therapeutic diet may be unable to reverse the microbiota alteration leading to persistent impaired development or death. In addition, as enteric sepsis is a major cause of death in this context, identification of missing gut microbes to be tested as probiotics (live bacteria that confer a benefit to the host) to restore rapidly the healthy gut microbiota and prevent the gut pathogenic invasion is of foremost importance. In this study, stool samples of malnourished patients with kwashiorkor and healthy children were collected from Niger and Senegal and analyzed by culturomics and metagenomics. We found a globally decreased diversity, a decrease in the hitherto unknown diversity (new species isolation), a depletion in oxygen-sensitive prokaryotes including Methanobrevibacter smithii and an enrichment in potentially pathogenic Proteobacteria, Fusobacteria and Streptococcus gallolyticus. A complex of 12 species identified only in healthy children using culturomics and metagenomics were identified as probiotics candidates, providing a possible, defined, reproducible, safe, and convenient alternative to fecal transplantation to restore a healthy gut microbiota in malnourished children. Microbiotherapy based on selected strains has the potential to improve the current treatment of severe acute malnutrition and prevent relapse and death by reestablishing a healthy gut microbiota.

Characteristics of patients admitted to internal medicine departments with high serum cobalamin levels: results from a prospective cohort study.

In spite of its limited performance, cobalamin (Cb) level is frequently assessed in inpatients of internal medicine departments [1]. Although Cb testing is mostly ordered because a clinical deficiency is suspected, patientsmay presentwith unexpectedly high Cb levels, but little interest is given by physicians to this result. However, a significant number of screened patients have high Cb levels: high Cb levels have been reported as 14%, 18.5% and 20% in three monocentric studies [2–4]. Importantly, high Cb levels have been associated with several conditions, including cancer, liver and renal diseases, myeloproliferative syndrome and alcoholism [2–4]. The aim of this study was to describe the characteristics of patients hospitalised in internalmedicinedepartment andwhoexhibited high Cb levels in order to identify thepotential underlying causes for this in this population. The BDOSE study is a prospective multicentric study that was conducted in 25 French internal medicine departments within 21 French hospitals [5]. During the 6-week study period, all consecutive inpatients who had undergone a Cb blood-level test were enrolled. Our study was approved by the Ethics Committee of Hospital Necker (Paris, France), which waived the need for written consent because the study protocol did not impact on patient management. The following clinical and biological characteristics of the patients were routinely recorded: age, ethnicity, gender, body-mass index, alcoholism, history of previous or ongoingmalignancies, autoimmune disease, main categories of reasons for hospital admission (see Table 1), complete blood-cell count (including mean corpuscular volume, MCV), creatinine clearance (Modification of Diet in Renal Disease study equation, MDRD) and hepatic parameters. Patients with high Cb levels (i.e. higher than normal values) were compared to patients with normal Cb levels, while those with low Cb levels (i.e. lower than normal values) were excluded from the analysis. Conditions associated with high Cb levels [6] were retrospectively searched for in the charts of patients with a high Cb level. Results are expressed asmeans± SDs ormedians (IQR) according to the distribution of continuous variables. Students t-test was used to compare continuous variables. The χ or Fishers exact test was used to compare categorical variables. Statistical calculations were performed using SPSS V.17.0 (SPSS, Chicago, Illinois, USA) software. For all bilateral statistical tests, a p-value of b0.05 was considered statistically significant. Among 380 patients admitted to internalmedicine departments and for whom a Cb assay had been ordered during the study period, 69 (18%), 40 (10.5%) and 271 (71.5%) had, respectively, high, normal and

Paenibacillus phocaensis sp. nov., isolated from the gut microbiota of a healthy infant

Paenibacillus phocaensis sp. nov. strain mt24T (= CSUR P2238 = DSM 101777) is a Gram-negative, facultative anaerobic, spore-forming and motile bacilli. This strain was isolated from the stool sample of a healthy infant from Niger. Its genome was estimated to a size of 5 521 415 bp with a 53.54% GC content. It contains 4835 protein-coding genes and 89 RNAs, among which two were 16S rRNA genes. There were also 101 genes (2.09%) identified as ORFans.

Tessaracoccus massiliensis sp. nov., a new bacterial species isolated from the human gut

A new Actinobacterium, designated Tessaracoccus massiliensis type strain SIT-7T (= CSUR P1301 = DSM 29060), have been isolated from a Nigerian child with kwashiorkor. It is a facultative aerobic, Gram positive, rod shaped, non spore-forming, and non motile bacterium. Here, we describe the genomic and phenotypic characteristics of this isolate. Its 3,212,234 bp long genome (1 chromosome, no plasmid) exhibits a G+C content of 67.81% and contains 3,058 protein-coding genes and 49 RNA genes.

Campylobacter fetus Bacteremia Revealed by Cellulitis without Gastrointestinal Symptoms in the Context of Acquired Hypogammaglobulinemia: A Report of Three Cases

Campylobacter fetus bacteremia is rare and occurs mainly in patients with immunosuppression. This infection, which often involves secondary localizations has already been reported in some primary humoral immune deficiencies. We describe three cases of severe infection due to C. fetus with cellulitis at presentation, but without any gastrointestinal symptoms, occurring in patients with acquired hypogammaglobulinemia.

‘Urmitella timonensis’ gen. nov., sp. nov., ‘Blautia marasmi’ sp. nov., ‘Lachnoclostridium pacaense’ sp. nov., ‘Bacillus marasmi’ sp. nov. and ‘Anaerotruncus rubiinfantis’ sp. nov., isolated from stool samples of undernourished African children

We report here the main characteristics of five new species ‘Urmitella timonensis’ strain Marseille-P2918T (CSUR P2918), ‘Blautia marasmi’ strain Marseille-P2377T (CSUR P2377), ‘Lachnoclostridium pacaense’ strain Marseille-P3100T (CSUR P3100), ‘Bacillus marasmi’ strain Marseille-P3556T (CSUR P3556) and ‘Anaerotruncus rubiinfantis’ strain MT15T (CSUR P2276), which were isolated recently from stool samples taken from undernourished children in Niger and Senegal using microbial culturomics.

‘Khelaifiella massiliensis’, ‘Niameybacter massiliensis’, ‘Brachybacterium massiliense’, ‘Enterobacter timonensis’, ‘Massilibacillus massiliensis’, new bacterial species and genera isolated from the gut microbiota of healthy infants

The main characteristics of ‘Khelaifiella massiliensis’ strain Mt13T (= CSUR P1935, = DSM100591), ‘Niameybacter massiliensis’ strain Mt14T (= CSUR P1909, = DSM100592), ‘Brachybacterium massiliense’ strain MT5T (= CSUR P2240, = DSM101766), ‘Enterobacter timonensis’ strain mt20T (= CSUR P2201, = DSM 101775) and ‘Massilibacillus massiliensis’ strain Marseille-P2411T (= CSUR P2411, = DSM102838), new species isolated from the gut of healthy African infants, are presented.

Bacillus niameyensis sp. nov., a new bacterial species isolated from human gut

Bacillus niameyensis sp. nov. strain SIT3T (= CSUR P1266 = DSM 29725) is the type strain of B. niameyensis sp. nov. This Gram-positive strain was isolated from the digestive flora of a child with kwashiorkor and is a facultative anaerobic rod and a member of the Bacillaceae family. This organism is hereby described alongside its complete genome sequence and annotation. The 4  286  116 bp long genome (one chromosome but no plasmid) contains 4130 protein-coding and 66 RNA genes including five rRNA genes.

Bacillus kwashiorkori sp. nov., a new bacterial species isolated from a malnourished child using culturomics

Strain SIT6T was isolated from the fecal flora of a severely malnourished child as part of a broad “culturomics” study aiming to maximize the culture conditions for the in‐depth exploration of the human microbiota. An analysis of the 16S rRNA gene sequence showed that strain SIT6T shared 94.1% 16S rRNA gene sequence similarity with Bacillus thermoamylovorans DKPT (NR_029151), the phylogenetically closest type species. Colonies are creamy white, circular, 4–5 mm in diameter after cultivation at 37°C for 24 hr on 5% sheep blood‐enriched Colombia agar. Growth occurs at temperatures in the range of 25–56°C (optimally at 37°C). Strain SIT6T is a gram‐positive, facultative anaerobic rod and motile by means of peritrichous flagella and sporulating; it is catalase and oxidase positive. The 2,784,637‐bp‐long genome, composed of 16 contigs, has a G+C content of 35.19%. Of the 2,646 predicted genes, 2,572 were protein‐coding genes and 74 were RNAs. The major fatty acids are saturated species (15:0 iso, 16:0 and 17:0 anteiso). Of the 14 detected fatty acids, 11 are saturated, either linear or branched (iso and anteiso). Digital DNA–DNA hybridization (dDDH) estimation and average genomic identity of orthologous gene sequences (AGIOS) of the strain SIT6T against genomes of the type strains of related species ranged between 18.6% and 38.3% and between 54.77% and 65.50%, respectively. According to our taxonogenomics results, we propose the creation of Bacillus kwashiorkori sp. nov. that contains the type strain SIT6T (=CSUR P2452T, =DSM 29059T).