Gut bacteria and sarcopenia link questioned in Iranian aging study

A new correspondence published in Aging Clinical and Experimental Research raises pointed statistical and biological objections to a cross-sectional analysis that reported associations between twelve gut bacterial genera and sarcopenia among 293 older adults from the second wave of the Birjand Longitudinal Aging Study in Iran. The original study, published on 30 April 2026, had identified Akkermansia and Lactobacillus as positively associated with sarcopenia and Roseburia as inversely associated, and its authors framed the findings as evidence for a gut–muscle connection in aging.

The correspondence, written by Maajid Mohi Ud. Din Malik and Supriya S. Desai, acknowledges that the Iranian setting and the use of qPCR-derived absolute abundances are useful additions to a literature dominated by East Asian and European cohorts relying on 16S amplicon sequencing. But it argues that three distinct problems complicate the interpretation the original authors advanced, and that each one points toward a more mundane explanation than a genuine microbial role in muscle loss.

The first problem is an internal tension in the statistical evidence. After false discovery rate correction of the twelve Wilcoxon comparisons, none of the genera differed significantly between sarcopenic and non-sarcopenic participants, with the lowest adjusted p-value standing at 0.16 for Escherichia. Meanwhile, the multivariate logistic odds ratios for Akkermansia (1.07), Lactobacillus (1.08) and Roseburia (0.89) all cluster tightly around 1.00, with confidence intervals that just touch the null value. The correspondents argue that the gap between the FDR-null univariate results and the nominally significant regression terms is more likely a multiple-comparison artefact than a robust signal.

They also challenge the compositional statistics underlying the analysis. Although the study used qPCR log-CFU values for a fixed twelve-genus panel, the correspondents contend these remain compositional in the relevant sense: within a single DNA extract, the abundances are not independent of one another, and an increase in one taxon mechanically constrains the others. A centred log-ratio sensitivity analysis, they write, would show whether the reported coefficients survive appropriate scaling, but no such analysis was performed.

The second objection concerns body mass index. Sarcopenic participants in the dataset were considerably leaner than their non-sarcopenic counterparts, at 26.5 versus 30.7 kg/m², and BMI carried a large adjusted effect on sarcopenia (odds ratio 0.78) and on low skeletal muscle mass index (odds ratio 0.58, p < 0.001). The correspondents identify this as a known artefact of the AWGS height-squared adjustment: appendicular skeletal muscle mass divided by height squared is positively correlated with BMI, so leaner older adults are mechanically reclassified as having low muscle mass regardless of true sarcopenic biology, while BMI- or weight-adjusted indices behave in the opposite direction.

Combining this with a separate observation—that Akkermansia is inversely associated with BMI in most cohorts, including those the original authors themselves cite—the correspondents suggest the Akkermansia–sarcopenia link in this dataset could be partly a leanness signal masquerading as a muscle signal. They propose repeating the regression using ASM/BMI or ASM/weight as the muscle-mass index, ideally adding waist circumference or fat mass as covariates, and reporting whether the Akkermansia coefficient still reaches conventional significance.

The third objection is biological. The correspondents point to interventional evidence that runs counter to the cross-sectional pattern: in a placebo-controlled trial of 100 adults aged 60 and older, pasteurised Akkermansia muciniphila HB05 at 1.0 × 10¹⁰ cells per day for 12 weeks improved peak knee-extensor torque and circulating follistatin, and frail older adults showed increases in muscle mass and grip strength after 18 weeks of supplementation with Lactobacillus plantarum TWK10. The observation that higher abundance of these same genera tracks with sarcopenia is, at face value, the opposite of what those trials would predict.

As a more parsimonious interpretation, the correspondents invoke reverse causation: worsening gut barrier integrity in sarcopenia could drive compensatory mucin turnover and Akkermansia expansion, while decreased colonic transit and dietary monotony could reposition the Lactobacillus niche upward. In other words, sarcopenia may shape the microbiota rather than the other way around—a reframing that, they note, would change the claim of the original abstract and its proposed therapeutic implication.

Finally, the correspondence questions what the reported prediction models actually demonstrate. The published areas under the curve for sarcopenia (0.796) and low skeletal muscle mass index (0.899) appear, on inspection of the coefficient sizes, to be driven by age, sex and BMI rather than by the bacterial panel. The correspondents call for reporting the incremental AUC contributed by the microbiota alone, with or without the demographic block, so readers can see what the genera add. They close by outlining three steps by which the dataset could speak more clearly to the gut–muscle hypothesis: recasting the Akkermansia and Roseburia associations against a BMI-independent muscle index, applying compositional log-ratio analysis, and quantifying the panel’s incremental discrimination over demographics alone.

Subject of Research: Critique of a cross-sectional study linking gut microbiota genera to sarcopenia in older adults

Article Title: Correspondence for the article: “Association between gut microbiota and sarcopenia in older adults: a cross-sectional analysis from the second wave of the Birjand Longitudinal Aging Study (BLAS)”

Article References: Malik, M. M. U. D., & Desai, S. S. (2026). Correspondence for the article: “Association between gut microbiota and sarcopenia in older adults: a cross-sectional analysis from the second wave of the Birjand Longitudinal Aging Study (BLAS)”. Aging Clinical and Experimental Research, 38(1), Article 206. https://doi.org/10.1007/s40520-026-03430-3

Image Credits: AI Generated

DOI: 10.1007/s40520-026-03430-3

Keywords: gut microbiota, sarcopenia, older adults, Akkermansia, Lactobacillus, Roseburia, qPCR, compositional data, BMI adjustment, reverse causation, Birjand Longitudinal Aging Study, correspondence