Altered Bile Acid Profiles Linked to Advanced Chronic Kidney Disease

ALTERATIONS in bile acid metabolism may play an underappreciated role in the progression of chronic kidney disease (CKD), according to new research analysing serum and urine bile acid profiles in patients with advanced disease.

Dysbiosis of the gut microbiota is increasingly recognised as a contributor to systemic inflammation and the accumulation of uremic toxins in CKD. Bile acids, which are key metabolic products of gut bacteria, have been implicated in metabolic and inflammatory pathways, but their specific involvement in CKD remains poorly defined. To address this gap, researchers conducted a cross-sectional study comparing bile acid profiles in patients with advanced CKD and individuals with normal renal function.

The study included 29 patients with advanced CKD and 30 age- and sex-matched controls with normal renal function. Comprehensive profiling of serum and urinary bile acids was performed to assess differences between the groups and explore associations with kidney function.

Sulfate-Conjugated Bile Acids Increased in CKD

Total serum bile acid concentrations did not differ significantly between patients with CKD and controls. However, marked differences were observed in bile acid composition. Patients with CKD had significantly lower serum levels of unconjugated bile acids and substantially higher levels of sulfate-conjugated bile acids compared with individuals with normal renal function. These findings suggest altered bile acid processing or clearance in advanced kidney disease.

In contrast to serum findings, urinary bile acid excretion was markedly reduced in CKD. Total urinary bile acid levels, along with most bile acid subgroups, were significantly lower in patients with CKD, consistent with impaired renal handling of these metabolites.

Importantly, several specific serum bile acids showed significant associations with declining kidney function. Higher levels of ursodeoxycholic acid, chenodeoxycholic acid, and sulfate-conjugated bile acids were independently associated with lower estimated glomerular filtration rate, even after adjusting for demographic factors and diabetes status.

The authors conclude that while overall serum bile acid levels may remain unchanged, the composition and conjugation patterns of bile acids are significantly altered in advanced CKD. These findings support the concept that disrupted bile acid metabolism is linked to kidney disease progression.

Implications for Future CKD Research

Although limited by its small sample size and cross-sectional design, the study provides novel insights into bile acid dysregulation in CKD. The authors suggest that bile acid profiling could help clarify disease mechanisms and may point towards new therapeutic targets aimed at modulating gut–kidney metabolic pathways.

 

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Glycolytic Pathways Drive Systemic Inflammation in Dermatomyositis

METABOLIC reprogramming in the skin may fuel systemic inflammation in patients with dermatomyositis (DM), according to a new study, opening potential paths to novel therapies. Researchers used single-cell RNA sequencing and proteomic analysis to dissect the cellular landscape of DM skin lesions and link it to broader systemic immune activation.

Systemic Inflammation Rooted in Skin Fibroblasts

By mapping skin samples from adults with DM at single-cell resolution, the team uncovered that fibroblasts, not immune cells, emerge as the main signalling hub within inflamed skin. These so-called “inflammatory fibroblasts” showed strong activation of the type I interferon (IFN-I) pathway, a hallmark of immune dysregulation, and were linked to elevated expression of the chemokine CXCL10.

Importantly, the study identified a novel “CXCL10–glycolysis axis” as a core mechanism driving inflammation. Proteomic and transcriptomic data from both skin and blood suggested that increased glycolytic activity in inflammatory fibroblasts correlates with systemic inflammatory signals. This metabolic shift appears to amplify immune activation beyond the skin, linking local pathology to systemic disease burden.

In a preclinical model of autoimmune myositis, inhibiting glycolysis using 2‑deoxy‑D‑glucose (2DG) significantly reduced inflammation, supporting the idea that metabolic reprogramming is not just a bystander but a driver of disease. These findings suggest that targeting cellular metabolism, particularly glycolysis, might offer a promising new therapeutic avenue for DM.

Implications for Clinical Care and Future Research

The study challenges the traditional view that immune cells are the main culprits in DM skin inflammation, highlighting instead a central role for fibroblasts and metabolic dysfunction. The link between skin-level changes and systemic inflammation underscores the importance of holistic disease management. The authors call for further research into metabolism-targeted treatments and suggest integrating metabolomic and proteomic profiling into routine care to better stratify patients and personalise therapy.

 

 

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Diabetes Breakthrough: Fish Oil May Reverse Insulin Resistance

 Fish oil supplementation modified the profile of defense cells, shifting them from a pro-inflammatory to an anti-inflammatory state, effectively reversing a condition resembling type 2 diabetes.

A Brazilian study published in Nutrients suggests that fish oil may help reduce insulin resistance and improve glucose tolerance by influencing the body’s inflammatory response.

Funded by FAPESP, the study was conducted on rats that, while not obese, exhibited a condition resembling type 2 diabetes—a disorder marked by high blood sugar levels due to diminished insulin effectiveness.

As the authors explain, supplementation with omega-3 fatty acids such as those present in fish oil has been prescribed for individuals with cardiovascular problems and type 2 diabetes, but the effects of these nutrients on insulin resistance without obesity are poorly understood.

In this study, the researchers observed that administration of 2 grams of fish oil per kilogram of body weight (equivalent to 540 mg/g of eicosapentaenoic acid, or EPA, and 100 mg/g of docosahexaenoic acid, or DHA) three times per week for eight weeks reduced insulin resistance in non-obese rats, which also displayed improved levels of blood sugar, inflammatory markers and lipid features, including total cholesterol, LDL (“bad cholesterol”) and triglycerides.

Potential Implications for Diabetes Treatment

Although the findings resulted from preclinical trials, they offer hope for non-obese type 2 diabetes patients, or 10%-20% of the worldwide total with the disease.

“Our experiments involved Goto-Kakizaki [GK] rats, an animal model for non-obese type 2 diabetes. We found that insulin resistance can be reduced in these animals by modulating the inflammatory response so as to change the profile of defense cells [lymphocytes] from a pro-inflammatory state to an anti-inflammatory state. This process parallels the response of obese individuals with insulin resistance to omega-3 fatty acid supplementation,” said Rui Curi, Director of Butantan Institute’s Education Center, Professor of Interdisciplinary Graduate Studies in Health Sciences at Cruzeiro do Sul University (UNICSUL), and coordinator of the study.

Alterations in lymphocytes, white blood cells that orchestrate the adaptive immune response, tend to have an impact on other immune system cells, triggering a cascade effect. “In previous studies, we observed alterations in both lymphocytes and macrophages [large white blood cells that often reside in adipose tissue and are part of the innate immune system, engulfing and destroying pathogens] in non-obese rats with insulin resistance. In such cases, these cells produce more pro-inflammatory cytokines, as is central in obese people with diabetes,” Curi explained.

“The main aim of the study, therefore, was to find out whether supplementation with fish oil [rich in omega-3] could reverse specific alterations in lymphocytes that had been observed in previous research. Our findings increased our knowledge of the link between inflammation and insulin resistance in non-obese animals, confirming that this is a key factor in diabetes even in the absence of obesity,” said Renata Gorjão, last author of the article, and Co-Director of UNICSUL’s Program of Graduate Studies in Health Sciences.

Systemic inflammation

The investigation described in the Nutrients article, conducted during the PhD candidacy of Tiago Bertola Lobato, was part of a larger project  that is deepening scientists’ understanding of insulin resistance in non-obese animals.

According to Curi, obesity is a major risk factor for diabetes, albeit not the only one. In the case of non-obese diabetes patients, the primary hypothesis is that the cause is genetic. In an article published in the journal describe an investigation into the possibility that insulin resistance in the non-obese may also be linked to delayed intestinal transit.

“Most obese people have chronic low-level inflammation, which is known to affect the insulin signaling pathways. Adipose tissue, which is augmented in obesity, releases pro-inflammatory cytokines that affect the insulin signaling pathways, promoting insulin resistance. In the non-obese model, this impactful characteristic of adipose tissue is absent, but systemic inflammation is present,” Curi said.

Systemic inflammation in non-obese GK rats with insulin resistance was demonstrated by the group in a previous study published in the International Journal of Molecular Sciences.

In another article relating to the same project, the researchers reported an early breakdown of anti-inflammatory mechanisms in non-obese GK rats with insulin resistance. Lymph nodes (part of the immune system) in newly weaned 21-day-old GK pups already exhibited a reduction in markers of regulatory T-cells (Tregs, cells with anti-inflammatory characteristics). Other early inflammatory alterations were also observed in the rats. 

“Fish oil supplementation reversed this pro-inflammatory profile, displaying a significant anti-inflammatory effect and reducing polarization of Th1 and Th17 cells [lymphocyte subtypes that perform crucial functions in inflammation], followed by a rise in the percentage of Tregs, which can inhibit the activation of pro-inflammatory lymphocytes. Thus the action of omega-3 fatty acids on lymphocytes, modulating them from a pro-inflammatory state to an anti-inflammatory state, may have triggered the reduction in insulin resistance in these animals,” Lobato said.

Despite the good news, the researchers stressed that more research is needed to confirm their findings. “These studies involved well-established experimental models that mimic insulin resistance in non-obese individuals. Trials in humans are needed to estimate the ideal dose and the most indicated type of omega-3 fatty acid,” Curi said.

 

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