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. 2019 Jun 24;9(1):9084.
doi: 10.1038/s41598-019-45611-3.

Gut Microbiota Alteration is Characterized by a Proteobacteria and Fusobacteria Bloom in Kwashiorkor and a Bacteroidetes Paucity in Marasmus

Thi-Phuong-Thao Pham  1 , Maryam Tidjani Alou  1   2 , Dipankar Bachar  1 , Anthony Levasseur  1 , Souleymane Brah  3 , Daouda Alhousseini  3 , Cheikh Sokhna  4 , Aldiouma Diallo  4 , Frank Wieringa  5 , Matthieu Million  6 , Didier Raoult  7
Affiliations

Gut Microbiota Alteration is Characterized by a Proteobacteria and Fusobacteria Bloom in Kwashiorkor and a Bacteroidetes Paucity in Marasmus

Thi-Phuong-Thao Pham et al. Sci Rep. .

Retraction in

Abstract

Kwashiorkor and marasmus are considered to be two different clinical diseases resulting from severe malnutrition, but this distinction has been questioned. In a previous study comparing children with kwashiorkor and healthy children from Niger and Senegal, we found a dramatic gut microbiota alteration with a predominant depletion of anaerobes and enrichment in Proteobacteria and Fusobacteria in kwashiorkor. However, it remained unknown whether this association was related to malnutrition or was a specific feature of kwashiorkor. In this continuation study, we added 7 new marasmus subjects and 71,162 new colonies from the same countries. Our results showed that, compared to marasmus, the kwashiorkor gut microbiota was characterized by an increased proportion of Proteobacteria (culturomics, Marasmus 5.0%, Kwashiorkor 16.7%, p < 0.0001; metagenomics, Marasmus 14.7%, Kwashiorkor 22.0%, p = 0.001), but there was a decreased proportion of Bacteroidetes in marasmus (culturomics, Marasmus 0.8%, Kwashiorkor 6.5%, p = 0.001; metagenomics, Marasmus 5.4%, Kwashiorkor 7.0%, p = 0.03). Fusobacterium was more frequently cultured from kwashiorkor. All detected potential pathogenic species were enriched in the kwashiorkor gut microbiota. These results provide a biological basis to support the usage of an antibiotic therapy more effective in suppressing the overgrowth of bacterial communities resistant to penicillin, combined with antioxidants and probiotics for nutritional recovery therapies, particularly for kwashiorkor.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Meta-analysis results of studies analysing the differences in intermediary metabolism patterns between KW and MRS (only significant results are shown).
Figure 2
Figure 2
Analysis of gut microbial diversity revealed a decreasing gradient from controls to children with marasmus and kwashiorkor. Scatter plots visually display gradients across the 3 groups in descending order, from controls (CTL) to children with marasmus (MRS) to kwashiorkor (KW). (A–C) Culturomics: A/global β-diversity (U/T ratio, see methods), Cochran-Armitage trend test, p = 0.0002; B/anaerobic β-diversity, p = 0.0002; C/aerotolerant β-diversity, p = 0.001. (D–F) Metagenomics. The decreasing gradient was significant for culturomics results (A–C) but not for metagenomics results (D–F).
Figure 3
Figure 3
PCoA analysis of gut microbiota diversity among kwashiorkor and marasmus subjects. The 3 charts are allowing us to visualize the proximities between kwashiorkor and marasmus subjects. For culturomics (A), there was a clear distance between 2 groups (KW and MRS) In metagenomics, analysis based on the relative abundance (B) and on the detection (C) of each species in each group showed that the clustering was not observed. The colour coded as red for MRS group and blue for KW group.
Figure 4
Figure 4
Phylum distribution in culturomics and metagenomics. Culturomics and metagenomics results confirmed a significant increase in Proteobacteria in kwashiorkor (uncorrected chi-square test, CTL-KW, MRS-KW, p < 0.001) as well as a significant decrease in Bacteroidetes in marasmus (uncorrected chi-square test, CTL-MRS, MRS-KW, p < 0.0005). Strikingly, the increased Fusobacteria diversity in kwashiorkor observed by metagenomics was also confirmed in kwashiorkor, but not in marasmus, by culturomics (uncorrected chi-square test, CTL-KW, p = 0.004).
Figure 5
Figure 5
Increased frequency of species in kwashiorkor and marasmus samples identified by the culturomics approach. Each bar represents the relative difference for each species, with red bars representing an increased frequency in patients with kwashiorkor and green bars representing an increased frequency in patients with marasmus. The grey bars represent oxygen tolerant species and the black bars represent obligate anaerobes. Proteobacteria (in orange) and potential pathogenic bacteria (p) were enriched in kwashiorkor but not in marasmus. **p-value ranging from 0.001–0.01; *p-value ranging from 0.01–0.05 (two-tailed chi-square test, Fisher’s exact test).
Figure 6
Figure 6
Increased frequency of species in kwashiorkor and marasmus samples identified by the metagenomics approach. Mean rank values of species representing differences in relative abundance were compared between kwashiorkor and marasmus samples. The red bars represent an increased abundance in patients with kwashiorkor, while the green bars represent an increased abundance in Marasmus. The grey bars represent oxygen tolerant species and the black bars represent obligate anaerobes. Proteobacteria (in orange) and potential pathogenic bacteria (p) were enriched in kwashiorkor but not in marasmus. *p-value ranging from 0.01–0.05 (Mann-Whitney test).
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