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I am grateful to Dr Young Ho Lee1 for response to my article.2 Although my study demonstrated non-causal association between gut microbiome and the risk of rheumatoid arthritis (RA), the author demonstrated significant association between them.
First, the reason why different conclusions were drawn from two studies is that I extracted only ‘Gut microbiota (bacterial taxa) (unit decrease)’ from variables of exposures in harmonised dataset before conducting Mendelian randomisation (MR) (R script is in online supplementary file), because other exposures did not have significant association with the risk of RA in the preliminary analysis. This additional operation brought less single nucleotide polymorphisms as instrumental variables in my study and the different result of ‘leave-one-out analysis’, in particular the influence of rs1230666 (MAGI3) on MR estimate. In addition, although the author demonstrated significant association by both inverse-variance weighted (IVW) and MR-Egger regression analyses, it does not mean that gut dysbiosis might cause the development of RA because beta were less than zero (if dysbiosis has causal effect against the development of RA, beta might be positive value).
More importantly in this instance, as commented in response from Alpizar-Rodriguez et al to my correspondence,3 to conclude causal association of dysbiosis against RA by MR, we need more appropriate genome-wide association study dataset which represent a relevant measure of dysbiosis in RA. To my knowledge, no study has found strong influence of genetics on specific bacterial taxa which is considered to be involved in the pathogenesis of RA, such as Prevotella spp abundance.4 5 Thus, to interpret the result of MR appropriately, we don’t have enough evidence to conclude causal effect of dysbiosis against the risk of RA yet. However, considering gut is one of the main sites of immune response, it is reasonable to accept the concept that dysbiosis could trigger RA. Further investigation with refined approach is required to clarify this question.
Handling editor Josef S Smolen
Contributors All the conceptualisation and writing were conducted by JI.
Funding The author has not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Commissioned; internally peer reviewed.
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