Clinical evidence of the role of Methanobrevibacter smithii in severe acute malnutrition

Abstract

Gut microbial dysbiosis has been shown to be an instrumental factor in severe acute malnutrition (SAM) and particularly, the absence of Methanobrevibacter smithii, a key player in energy harvest. Nevertheless, it remains unknown whether this absence reflects an immaturity or a loss of the microbiota. In order to assess that, we performed a case-control study in Mali using a propensity score weighting approach. The presence of M. smithii was tested using quantitative PCR on faeces collected from SAM children at inclusion and at discharge when possible or at day 15 for controls. M. smithii was highly significantly associated with the absence of SAM, detected in 40.9% controls but only in 4.2% cases (p < 0.0001). The predictive positive value for detection of M. smithii gradually increased with age in controls while decreasing in cases. Among children providing two samples with a negative first sample, no SAM children became positive, while this proportion was 2/4 in controls (p = 0.0015). This data suggests that gut dysbiosis in SAM is not an immaturity but rather features a loss of M. smithii. The addition of M. smithii as a probiotic may thus represent an important addition to therapeutic approaches to restore gut symbiosis.

Figure 1

Study flow-chart. (a) Case selection, malnourished children are selected based on the WHO severity criterion and before any treatment; the presence of any symptoms or infection was not an exclusion criterion, (b) Control selection, healthy children are selected based on WHO standard without symptoms and antibiotics into the last 15 days.

Figure 2

Absolute concentration of Methanobrevibacter smithii and other keys species. Species were quantified using real-time PCR in all samples and compared between healthy controls (green points) and children with severe acute malnutrition (red points).

Figure 3

Age group detection of Methanobrevibacter smithii in malnourished and healthy children. Proportion of positive children is shown in each age range, green bar represents healthy control and red bar malnourished children.

Figure 4

Positive predictive value of Methanobrevibacter smithii in healthy and malnourished children according to age. Probability of detection of M. smithii relating to age is shown in healthy controls (CTL) and severely malnourished children (SAM); spike bars represent all the individuals from whom M. smithii has been detected in each group in the age range from 0 to 59 months. Green spike bars represent healthy controls children in top with the associated predictive value below. Red spike bars represent cases with the associated predictive value below.

Figure 5

DNA concentration of Methanobrevibacter smithii in healthy and severely malnourished children according to age. Linear regression model representing DNA concentrations (log₁₀ DNA copies on the Y axis) according to the age of the subject (in months on the X axis). Regression lines are represented separately for each group and its 95% interval confidence range (coefficient of determination r² of 0.29 and 0.006 for controls samples and SAM samples respectively) with the green points and line representing healthy children and the red points and line representing severely malnourished children.