Elevated fecal calprotectin is associated with gut microbial dysbiosis, altered serum markers and clinical outcomes in older individuals Original paper

What was studied?

This study examined fecal calprotectin gut dysbiosis in older adults by testing whether higher fecal calprotectin (a stool marker of intestinal neutrophil-driven inflammation) is linked to specific gut microbiome shifts, systemic serum signals, and real-world clinical outcomes. In 728 participants from the TREND cohort, investigators stratified fecal calprotectin into low (≤50 μg/g), moderate (>50–100 μg/g), and high (>100 μg/g) groups, then compared gut microbial genera (16S rRNA sequencing), inferred microbial functional pathways (PICRUSt2), serum inflammatory proteins (92-marker Olink panel), and targeted serum metabolomics (135 detected metabolites). They also assessed lifestyle variables, medication exposures (notably PPIs and NSAIDs), and clinical phenotypes, including BMI/obesity and cardiovascular history.

Who was studied?

Participants were community-dwelling older adults from the prospective TREND study, with stool and serum collected at wave 4 (2015/2016). The analytic sample included 728 individuals (mean age ~68.7 years; range 53–86) after excluding samples missing calprotectin and excluding extreme outliers (>400 μg/g) to reduce the chance that acute infection or undiagnosed inflammatory bowel disease dominated results. The cohort was recruited from the general population but enriched for neurodegenerative risk factors (e.g., lifetime depression, olfactory loss, REM sleep behavior disorder), which the authors accounted for when interpreting clinical associations.

Most important findings

High fecal calprotectin was associated with a clear dysbiosis pattern characterized by increased pro-inflammatory or inflammation-tolerant genera (notably gram-negative Haemophilus and Veillonella, and increased Streptococcus) and decreased short-chain fatty acid (SCFA)–producing taxa (including Blautia, Turicibacter, and multiple Clostridium groups). Despite these compositional shifts, α- and β-diversity did not significantly differ after covariate adjustment, suggesting that the key signal was which taxa changed, not overall diversity. Functionally, inferred pathways suggested reduced fermentation routes linked to SCFA generation (e.g., heterolactic fermentation and Bifidobacterium shunt), alongside mixed shifts in other carbohydrate and energy pathways. Systemically, the high-calprotectin group showed increased serum IL-17C and CCL19, consistent with heightened epithelial/immune signaling, and a strong increase in indoxyl sulfate, a microbiome-derived tryptophan metabolite with cardiotoxic/uremic properties. Importantly, the calprotectin–indoxyl sulfate association showed significant microbiome mediation (global and genus-specific), implicating taxa such as Haemophilus, Veillonella, Blautia, Clostridium XIVa, and Turicibacter in linking gut inflammation to circulating toxin burden. Clinically, higher calprotectin tracked with higher BMI and obesity prevalence and a greater history of heart attack, aligning gut inflammatory activity with cardiometabolic risk.

Key implications

For clinicians, fecal calprotectin in older adults may function as more than an IBD screening marker: levels >100 μg/g can flag a pro-inflammatory microbiome signature with depletion of SCFA-producing genera and enrichment of potential pathobionts, coupled to systemic immune signaling and elevated indoxyl sulfate. This pattern supports a plausible gut-cardiometabolic axis in aging, especially since obesity, PPI/NSAID exposure, and prior heart attack clustered with higher calprotectin. Practically, an elevated result could justify a structured evaluation of reversible drivers (medications, diet/fiber patterns, constipation/inactivity), cardiometabolic risk optimization, and—when clinically appropriate—further GI workup to exclude occult pathology while recognizing that moderate elevations may still carry systemic relevance.

Citation

Heinzel S, Jureczek J, Kainulainen V, et al. Elevated fecal calprotectin is associated with gut microbial dysbiosis, altered serum markers and clinical outcomes in older individuals. Sci Rep. 2024;14:13513. doi:10.1038/s41598-024-63893-0