This study will test whether inulin, a type of dietary fiber, can reduce inflammation in older adults with knee osteoarthritis. Inflammation in the body may contribute to both joint pain and the progression of osteoarthritis. Inulin is a prebiotic fiber that may improve gut health and reduce lipopolysaccharide (LPS), a marker of bacterial products in the blood that is linked to inflammation.

In this trial, participants with knee osteoarthritis will be randomly assigned to receive either inulin or a placebo (maltodextrin) for 8 weeks. The study will measure changes in blood LPS levels, knee pain, and other markers of inflammation. The goal is to determine whether inulin supplementation can improve pain and reduce inflammation in people with knee osteoarthritis.

Knee osteoarthritis (OA) is a leading cause of pain and disability among older adults. Low-grade systemic inflammation has been implicated in OA pathogenesis, and bacterial products such as lipopolysaccharide (LPS) translocated from the gut microbiome may contribute to joint inflammation. Inulin-type fructans are non-digestible carbohydrates classified as prebiotic fibers. By modulating the gut microbiome, inulin has been shown to promote the growth of beneficial bacteria and to increase short-chain fatty acid (SCFA) production, which may help reduce systemic LPS levels and inflammation.

This is a single-center, randomized, double-blind, placebo-controlled clinical trial of participants aged 40 years or older with radiographically confirmed knee OA and significant knee pain. Participants will be randomized in a 1:1:1 ratio to receive 10 g/day inulin, 15 g/day inulin, or placebo (maltodextrin) for 8 weeks. The primary outcome is change in serum LPS from baseline to 8 weeks in the combined inulin groups compared to placebo.

The study hypothesis is that inulin supplementation will reduce circulating LPS and improve knee pain outcomes, supporting the role of gut microbiome modulation in the management of OA-related inflammation.

Inclusion Criteria:

• Provision of signed and dated informed consent form.
• Stated willingness to comply with all study procedures and availability for the duration of the study (8 weeks).
• Male or female, aged ≥ 40 years.
• Established patient in the VA Connecticut Healthcare System
• At least one knee with pain severity in the past week ≥ 4/10 on numerical rating scale (NRS)
• Self-reported knee pain on most days of the prior month.
• Diagnosed with knee osteoarthritis (Kellgren-Lawrence grade 2-4 on radiographic imaging within the past 2 years).
• Ability to take oral powder supplements and willingness to adhere to the inulin/placebo daily regimen.
• Agreement to adhere to lifestyle considerations (see Section 5.3) throughout study duration, including maintenance of current diet, physical activity, and avoidance of new dietary supplements or complementary therapies.
• English-speaking and able to provide informed consent.
• For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to continue such method during study participation.

Exclusion Criteria:

• Current diagnosis of pre-diabetes (impaired glucose tolerance) or diabetes mellitus (Type 1 or Type 2).
• Use of antibiotics within the past 6 months.
• Current use of medications known to significantly impact the gut microbiome (e.g., proton pump inhibitors, disease-modifying antirheumatic drugs, GLP-1 receptor agonists).
• Use of anti-inflammatory dietary supplements (e.g., turmeric, omega-3 fatty acids) within the past 30 days.
• Participation in another interventional study or use of an investigational drug within the past 30 days.
• Current use of complementary or integrative therapies for knee OA including tai chi, acupuncture or yoga.
• Known allergy or intolerance to components of the study intervention, including inulin or maltodextrin.
• The presence of significant gastrointestinal disease that may interfere with the intervention or outcomes, such as inflammatory bowel disease or active peptic ulcer disease.
• Any medical, psychological, or behavioral condition that, in the opinion of the investigators, would place the participant at undue risk, interfere with study participation or adherence, or compromise data integrity.
• Current diagnosis of alcohol use disorder
• Pregnancy

Individual participant data will not be shared because the study is conducted within the Veterans Affaire system, which prohibits release of participant-level data outside of the VA firewall. However, de-identified aggregate group-level data, study protocol, data collection instruments, and analytic code will be made available to qualified researchers upon request in accordance with NIH Data Management and Sharing policy.

Inulin and placebo are identical in appearance, taste, and packaging. Randomization is managed by the investigational pharmacy; study staff, investigators, and participants remain blinded.