Walnuts Up Insulin Response, Cut Gut Permeability in Obesity

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Walnut consumption modified the fecal microbiota and metabolome, improved insulin response and reduced gut permeability in adults with obesity, a small study showed.

“Less than 10% of adults are meeting their fiber needs each day, and walnuts are a source of dietary fiber, which helps nourish the gut microbiota,” study coauthor Hannah Hoscher, PhD, associate professor at the University of Illinois at Urbana-Champaign, told Medscape Medical News.

Hoscher and her colleagues previously conducted a study on the effects of walnut consumption on the human intestinal microbiota “and found interesting results,” she said. Among 18 healthy men and women with a mean age of 53 years, “walnuts enriched intestinal microorganisms, including Roseburia that provide important gut-health promoting attributes, like short-chain fatty acid production. We also saw lower proinflammatory secondary bile acid concentrations in individuals that ate walnuts.”

The current study, presented at NUTRITION 2025 in Orlando, Florida, found similar benefits among 30 adults with obesity but without diabetes or gastrointestinal disease.

Walnut Halves, Walnut Oil, Corn Oil — Compared

The researchers aimed to determine the impact of walnut consumption on the gut microbiome, serum and fecal bile acid profiles, systemic inflammation, and oral glucose tolerance to a mixed-meal challenge.

Participants were enrolled in a randomized, controlled, crossover, complete feeding trial with three 3-week conditions, each identical except for walnut halves (WH), walnut oil (WO), or corn oil (CO) in the diet. A 3-week washout separated each condition.

“This was a fully controlled dietary feeding intervention,” Hoscher said. “We provided their breakfast, lunch, snacks and dinners — all of their foods and beverages during the three dietary intervention periods that lasted for 3 weeks each. Their base diet consisted of typical American foods that you would find in a grocery store in central Illinois.”

Fecal samples were collected on days 18-20. On day 20, participants underwent a 6-hour mixed-meal tolerance test (75 g glucose + treatment) with a fasting blood draw followed by blood sampling every 30 minutes.

The fecal microbiome and microbiota were assessed using metagenomic and amplicon sequencing, respectively. Fecal microbial metabolites were quantified using gas chromatography-mass spectrometry.

Blood glucose, insulin, and inflammatory biomarkers (interleukin-6, tumor necrosis factor-alpha, C-reactive protein, and lipopolysaccharide-binding protein) were quantified. Fecal and circulating bile acids were measured via liquid chromatography tandem mass spectrometry.

Gut permeability was assessed by quantifying 24-hour urinary excretion of orally ingested sucralose and erythritol on day 21.

Linear mixed-effects models and repeated measures ANOVA were used for the statistical analysis.

The team found that Roseburia spp were greatest following WH (3.9%) vs WO (1.6) and CO (1.9); Lachnospiraceae UCG-001 and UCG-004 were also greatest with WH vs WO and CO.

WH fecal isobutyrate concentrations (5.41 µmol/g) were lower than WO (7.17 µmol/g) and CO (7.77). Similarly, fecal isovalerate concentrations were lowest with WH (7.84 µmol/g) vs WO (10.3µmol/g) and CO (11.6 µmol/g).

In contrast, indoles were highest in WH (36.8 µmol/g) vs WO (6.78 µmol/g) and CO (8.67µmol/g).

No differences in glucose concentrations were seen among groups. The 2-hour area under the curve (AUC) for insulin was lower with WH (469 µIU/mL/min) and WO (494) vs CO (604 µIU/mL/min).

The 4-hour AUC for glycolithocholic acid was lower with WH vs WO and CO. Furthermore, sucralose recovery was lowest following WH (10.5) vs WO (14.3) and CO (14.6).

“Our current efforts are focused on understanding connections between plasma bile acids and glycemic control (ie, blood glucose and insulin concentrations),” Hoscher said. “We are also interested in studying individualized or personalized responses, since people had different magnitudes of responses.”

In addition, she said, “as the gut microbiome is one of the factors that can underpin the physiological response to the diet, we are interested in determining if there are microbial signatures that are predictive of glycemic control.”

Because the research is still in the early stages, at this point, Hoscher simply encourages people to eat a variety of fruits, vegetables, whole grains, legumes and nuts to meet their daily fiber recommendations and support their gut microbiome.

This study was funded by a USDA NIFA grant. No competing interests were reported.

Marilynn Larkin, MA, is an award-winning medical writer and editor whose work has appeared in numerous publications, including Medscape Medical News and its sister publication MDedge, The Lancet (where she was a contributing editor), and Reuters Health.