Resistant starch (RS) consumption can have beneficial effects on human health, but the response, in terms of effects on the gut microbiota and host physiology, varies between individuals. Factors predicting the response to RS are not yet established and would be useful for developing precision nutrition approaches that maximize the benefits of dietary fiber intake. We sought to identify predictors of gut microbiota response to RS supplementation. We enrolled 76 healthy adults into a seven-week crossover study. Participants consumed RS type 2 (RS2), RS type 4 (RS4), and a digestible starch, for ten days each with five-day washout periods in between. We collected fecal and saliva samples and food records before and during each treatment period. We performed 16S rRNA gene sequencing and measured fecal short-chain fatty acids (SCFAs), salivary amylase gene copy number, and salivary amylase activity (SAA). Dietary fiber intake was predictive of relative abundance of several amplicon sequence variants (ASVs) at the end of both RS treatments. Treatment order (the order of consumption of RS2 and RS4), alpha diversity, and a subset of ASVs were predictive of SCFA changes after RS supplementation. SAA was only predictive of the relative abundance of ASVs after digestible starch supplementation. Based on our findings, dietary fiber intake and gut microbiome composition would be informative if assessed prior to recommending RS supplementation. Using a precision nutrition approach to optimize the benefits of dietary fibers such as RS could be an effective strategy to compensate for the low consumption of dietary fiber nationwide.

The authors have declared no competing interest.

NCT05743790

This study was funded in part by a President's Council of Cornell Women Award (ACP) and the National Institutes of Health under award T32-DK007158 (DKS).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

All human-related procedures and sample and data collection were approved by the Cornell University Institutional Review Board for Human Participant Research (Protocol Number: 1902008575) prior to recruitment and enrollment of participants.

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I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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The raw fastq sequences generated from the 16S rRNA amplicon sequencing will be available in the National Center for Biotechnology Information Sequence Read Archive via the project number PRJNA944997 upon publication of the manuscript in a peer-reviewed journal.

http://www.ncbi.nlm.nih.gov/bioproject/944997