Breakthrough in the INSPIRE Trial: Prebiotic Fibres Target Knee Osteoarthritis Pain

The University of Nottingham's latest research has uncovered a promising avenue for managing knee osteoarthritis (OA), a condition affecting millions in the UK and causing chronic pain and mobility issues. Through the INSPIRE trial—lIfestyle iNterventionS for PaIn ReliEf—scientists demonstrated that a simple daily prebiotic fibre supplement, inulin, significantly alleviates pain, enhances grip strength, and reduces overall pain sensitivity. This study, published in the journal Nutrients in February 2026, highlights how modulating the gut microbiome could revolutionise non-pharmacological treatments for this degenerative joint disease.

Knee OA, characterised by cartilage breakdown in the knee joint leading to pain, stiffness, and reduced function, impacts over 5.4 million adults in England alone, according to Versus Arthritis data. Traditional management relies on painkillers with side effects or joint replacements, but adherence to exercise therapies remains low. The Nottingham team's work shifts focus to the gut, where trillions of microbes influence systemic inflammation and pain perception via short-chain fatty acids (SCFAs) like butyrate.

Unpacking the INSPIRE Trial Methodology and Participant Profile

Conducted as a rigorous two-by-two factorial randomised controlled trial (RCT), the INSPIRE study involved 136 community-dwelling adults aged over 50 with symptomatic knee OA, of whom 117 completed the six-week intervention on a per-protocol basis. Participants, averaging 67.5 years old with a body mass index (BMI) of 29.5 kg/m², were randomly assigned to one of four groups: 20 grams per day of inulin powder, digital physiotherapy-supported exercise (PSE) via the Joint Academy app, a combination of both, or a placebo (10 grams maltodextrin).

Inulin, a non-digestible carbohydrate naturally found in chicory root, garlic, onions, and Jerusalem artichokes, was mixed into breakfast yogurt or drinks. PSE consisted of tailored home exercises and educational modules delivered digitally, promoting adherence without clinic visits. Outcomes were measured using validated tools: Numerical Rating Scale (NRS) for pain (primary), 30-second sit-to-stand test (30-CST), timed up-and-go (TUG), handgrip dynamometry, and quantitative sensory testing for pain sensitivity including pressure pain thresholds (PPT) and temporal summation.

Serum levels of SCFAs (acetate, propionate, butyrate) and glucagon-like peptide-1 (GLP-1)—a gut hormone regulating appetite and inflammation—were analysed via liquid chromatography-high resolution mass spectrometry (LC-HRMS) and enzyme-linked immunosorbent assay (ELISA). The trial, blinded for the supplement arm, was approved by the University of Nottingham's ethics committee and registered on ISRCTN (ISRCTN91381296).

Key Results: Inulin's Edge in Pain Relief and Functional Gains

Both interventions independently reduced knee pain, exceeding the minimal clinically important difference (MCID) of two points on the NRS. Inulin yielded a baseline-adjusted mean difference (Δ) of -1.11 (95% CI -2.18 to -0.04, p=0.045) versus placebo, while PSE achieved -1.55 (95% CI -2.52 to -0.58, p=0.002). Notably, inulin uniquely boosted grip strength by 4.62 kg (p=0.002), improved PPT at the knee and forearm (p=0.009), and diminished temporal summation (p=0.025), indicating reduced central pain sensitisation.

• PSE enhanced mobility: 30-CST improved by 2.76 repetitions (p=0.0004), TUG by 0.66 seconds (p=0.02).
• Inulin increased serum butyrate (p=0.025) and GLP-1 (p=0.011), with higher GLP-1 correlating to better grip strength (β=0.25, p=0.006).
• Responder analysis showed 52% in inulin group achieved ≥2-point pain reduction versus 28% placebo.

Adherence shone for inulin, with just 3.6% dropout compared to 21% for PSE (p<0.01), underscoring its practicality for public health.

The Science Behind Inulin: Modulating the Gut Microbiome for Pain Control

Inulin acts as a prebiotic, selectively feeding beneficial gut bacteria like Bifidobacterium and Faecalibacterium, which ferment it into SCFAs. Butyrate, the standout in this study, exerts anti-inflammatory effects by inhibiting histone deacetylases (HDACs), reducing pro-inflammatory cytokines like IL-6 and TNF-α implicated in OA progression. This gut-joint axis influences pain via vagus nerve signalling and blood-brain barrier modulation, dampening hypersensitivity.

GLP-1's role emerged as novel: released by enteroendocrine L-cells in response to SCFAs, it not only curbs appetite but enhances muscle function and analgesia, potentially via central nervous system pathways. Nottingham researchers, building on prior work linking low faecalibacterium to chronic pain, posit a 'gut-muscle-pain axis' where microbial metabolites bolster physical resilience against age-related decline.

For context, the UK hosts 10.5 million OA cases, with knee OA costing the NHS £2.7 billion yearly. Prebiotics offer a low-cost, side-effect-free alternative, aligning with NICE guidelines emphasising lifestyle interventions.

Photo by Andrey Khoviakov on Unsplash

Physiotherapy's Complementary Role and Why Supplements May Win on Adherence

PSE, rooted in evidence-based strengthening and neuromuscular training, improved functional mobility but faltered on adherence—21% dropout reflecting real-world barriers like motivation and access. Digital delivery mitigated some issues, yet inulin's simplicity prevailed, fitting seamlessly into routines without time commitment.

No synergistic effects were observed between arms, suggesting additive potential in clinical practice. This mirrors broader trends: only 30% of OA patients sustain long-term exercise, per Arthritis UK surveys, versus near-perfect supplement compliance here.

Expert Insights from Nottingham's Leading Researchers

Dr Afroditi Kouraki, lead author from the NIHR Nottingham Biomedical Research Centre (BRC), stated: "Our findings suggest that targeting gut health with a prebiotic supplement is a safe, well-tolerated, and effective way to reduce pain in people with knee osteoarthritis. The very low dropout rate compared to the exercise group is also encouraging from a public health perspective—people were able to fit this supplement easily into their daily lives."

Senior author Professor Ana Valdes, Professor of Rheumatic Diseases and expert in gut microbiome-OA links, added: "The link we observed between GLP-1 and grip strength is particularly intriguing and points to a broader gut-muscle-pain axis that warrants further investigation. This could have implications not just for osteoarthritis, but for understanding how gut health influences ageing and physical resilience more broadly."

Professor Lucy Donaldson of Versus Arthritis echoed: "Researchers are starting to explore the role of the gut microbiome in our experience of pain. This exciting preliminary research highlights how diet and physiotherapy can act in different ways to have benefits for people with arthritis."

University of Nottingham's Legacy in Osteoarthritis and Microbiome Research

Nottingham's School of Medicine hosts the Versus Arthritis Pain Centre and NIHR BRC, pioneering OA studies. Professor Valdes' team has linked gut dysbiosis to hand OA symptoms and metabolic syndrome-pain interactions. Prior work includes exercise-induced endocannabinoids for pain relief and gout microbiome insights.

Ranked 7th in UK research power (REF 2021), Nottingham attracts NIHR funding, fostering PhD and postdoc opportunities in nutrigenomics and pain science. This positions it as a hub for translational research, bridging lab discoveries to patient benefits via clinical trials like INSPIRE.

Implications for Arthritis Management and Public Health in the UK

With OA prevalence rising 20% by 2035 due to ageing populations, inulin-like interventions could ease NHS burdens. Costing pennies daily, prebiotics democratise relief, especially for underserved rural patients. Integrating with GP-prescribed apps could enhance holistic care.

Beyond OA, findings suggest gut health's role in sarcopenia and frailty, prompting dietary guidelines updates. Real-world trials and long-term studies are next, potentially reshaping NICE OA pathways.

Photo by The Worthy Goods on Unsplash

Actionable Insights: Incorporating Prebiotics into Daily Life

• Start with 10-20g inulin daily via powder or foods like chicory root; consult GP if IBS-prone.
• Combine with PSE apps for synergistic gains.
• Monitor via food diaries; expect benefits in 4-6 weeks.
• UK sources: health stores or online, £10-15/month.

While promising, supplements complement—not replace—medical advice. Patients should discuss with rheumatologists.

Future Directions: Expanding the Gut-Joint Axis Research

Nottingham plans larger trials testing inulin strains, dosages, and diverse populations including rheumatoid arthritis. Microbiome sequencing and metabolomics will elucidate mechanisms. Collaborations with pharma could yield targeted prebiotics.

For aspiring researchers, Nottingham offers MSc/PhD in Human Nutrition and Pain Science, linking to academic career advice. Discover professor ratings on Rate My Professor.

This study exemplifies UK higher education's impact on global health challenges.