Xifaxan (rifaximin)

Xifaxan (rifaximin) is a non-systemic antibiotic primarily used for gastrointestinal conditions such as small intestinal bacterial overgrowth (SIBO), irritable bowel syndrome with diarrhea (IBS-D), and hepatic encephalopathy. Unlike many antibiotics, rifaximin is poorly absorbed into the bloodstream and acts mainly within the gut lumen. Because of this localized action, it is sometimes viewed as lower risk than systemic antibiotics, though it is still a prescription medication with meaningful biological effects.

In PFS/PSSD/PAS communities, rifaximin tends to appear in discussions focused on gut-based theories rather than direct hormonal or serotonergic manipulation. Mechanistically, interest centers on the gut–brain axis: intestinal bacteria can influence inflammation, neuroactive metabolite production, bile acids, tryptophan metabolism, and even neurosteroid signaling indirectly. Some hypotheses propose that persistent dysbiosis or SIBO could contribute to downstream nervous-system dysregulation, and that improving gut balance may relieve certain symptoms in a subset of people.

Anecdotes (Community Reports):

https://www.reddit.com/r/PSSD/comments/speqgn/did_you_try_xifaxan_rifaximin_this_is_the_main/

https://www.reddit.com/r/PSSD/comments/uc1a4w/sibo_and_xifaxan_pssd/

How to Interpret This Page

This page summarizes anecdotal reports and community observations, not medical evidence. “Risk” here refers to how frequently severe or prolonged symptom worsening is reported, not to proven causation or population-wide probability. Individual responses vary widely, and absence of issues in some users does not rule out significant reactions in others.

Community Reports: Mixed Outcomes & Variable Risk Signal

Across anecdotal reports, rifaximin shows mixed but generally modest outcomes. Some individuals report partial improvements after treatment—often described as better cognition, reduced anxiety, improved stress tolerance, or subtle sexual symptom improvement—especially when rifaximin is part of a broader gut-focused approach (diet changes, time, addressing SIBO triggers). Others report no noticeable change at all, and a smaller number report transient flares or worsening (e.g., fatigue, anxiety, GI instability), though reports of severe or permanent deterioration appear uncommon.

Importantly, when improvement is reported, it is rarely framed as a cure. More often, it is described as one contributing factor among many, and timing confounders are common (natural recovery over time, stopping other triggers, concurrent dietary changes). Because rifaximin alters gut ecology, responses can be highly individual, and benefit in one person does not generalize reliably to others.

Reported Risks / Reasons for Caution

Although rifaximin is considered relatively gut-localized, it is still an antibiotic and can meaningfully alter the microbiome. In some individuals, this shift may be neutral or helpful; in others, it may destabilize symptoms or contribute to relapse if underlying issues are not addressed. Repeated or inappropriate use may also contribute to resistance patterns or recurrent dysbiosis.

For people with PFS/PSSD/PAS—who often describe heightened sensitivity to physiological changes—rifaximin is best viewed as a moderate-complexity, clinician-supervised intervention, not a low-risk supplement. It is typically approached as part of a structured SIBO or gut-health evaluation rather than a standalone experiment.