This is a very interesting and potentially impactful study. It is good to see such translational human studies. However, there is a major scientific criticism central to this report regarding measurement of endotoxin from experimental subjects:

1. The methods of endotoxin detection are far to brief. Measurement of endotoxin in serum is challenging and not described in the product literature (in fact, the manufacturer states it is NOT designed to be used for in vivo measurement of endotoxin). Thus specifics of how this was done is critical for both scientific transparency and to assure scientific reproducibility.

2. An important control is lacking. What is the effect of ethanol on the limulus (LAL) endotoxin assay. At the least an in-vitro evaluation of the effect of ethanol on this assay should have been performed.

3. Similarly, as the "standard" curve for endotoxin quantitation is performed in endotoxin-free water, it is not clear what effect might be imparted by measurement in protein-rich serum (i.e. is absolute quantitation of endotoxin reliable in serum). At the least, endotoxin levels should have been measured again in LPS-spiked serum/plasma which was used to stimulate whole blood. This would assure similar LPS levels were produced in vitro as those endotoxin levels measured as in serum of experimental subjects.

Though the 16S RNA clearly support the translocation of bacteria, the levels of endotoxin are claimed to be "physiologic" based on the subsequent whole blood stimulation experiments and thus the study results overall rely heavily on the published serum endotoxin measurements.