Diabetic kidney disease (DKD) is one of the most common microvascular complications of diabetes and a leading cause of chronic kidney disease and end-stage renal failure worldwide. Conventional therapeutic strategies remain limited, prompting increasing interest in novel approaches targeting the gut microbiota–kidney axis. A study published in Food Bioscience in July 2025 reported that the next-generation probiotic Akkermansia muciniphila (Akk) significantly improved diabetic kidney disease in db/db mice by modulating gut microbiota composition and reducing oxidative stress and inflammatory responses. These findings provide new scientific evidence supporting microecological interventions for DKD. Accordingly, probiotic products containing Akkermansia muciniphila or incorporating this bacterium may represent a promising strategy for supporting metabolic health and managing multiple diseases.
Akkermansia muciniphila Improves Diabetic Kidney Disease
Diabetic kidney disease (DKD), one of the most common microvascular complications of diabetes, has become a leading cause of chronic kidney disease (CKD) and end-stage renal failure worldwide, significantly affecting quality of life and increasing mortality risk. Traditional intervention strategies remain limited, while the gut microbiota–kidney axis is emerging as a promising new direction in the field of metabolic kidney diseases.
A study published in Food Bioscience in July 2025 reported that a novel human-derived strain of Akkermansia muciniphila (Akk) significantly improved diabetic kidney disease in db/db mice by regulating the gut microbiota and suppressing oxidative stress and inflammation. These findings provide new scientific evidence for microecological interventions in DKD. Therefore, probiotic products based on Akkermansia muciniphila or containing an appropriate amount of Akk may become a new approach for improving various diseases.
Food Bioscience
Improvement Effects of AKK on DKD
The study established a type 2 diabetes and diabetic kidney disease model in db/db mice and administered AKK by gavage for eight weeks to evaluate its renal protective effects. The results showed that AKK not only significantly reduced fasting blood glucose levels and improved glucose intolerance in mice, but also effectively decreased serum triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels while increasing high-density lipoprotein cholesterol levels, demonstrating both glucose-lowering and lipid-regulating effects.
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Further findings showed that AKK significantly reduced blood urea nitrogen, serum creatinine, urinary albumin excretion, and the urinary albumin-to-creatinine ratio in mice, thereby improving renal function. At the same time, it alleviated structural abnormalities in the kidneys, including glomerular hypertrophy, renal tubular dilation, mesangial proliferation, and renal interstitial fibrosis, effectively reversing pathological kidney damage caused by diabetic kidney disease.
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Mechanisms by Which AKK Improves DKD
AKK exerts protective effects by reducing oxidative stress damage in the kidneys. It significantly decreases the level of malondialdehyde (MDA) in renal tissues while increasing the activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), thereby restoring the body's antioxidant defense system.
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In addition, AKK significantly inhibits activation of the renal TLR4/NF-κB inflammatory signaling pathway, downregulating the expression of phosphorylated NF-κB, TLR4, and MMP9 proteins, and reducing the secretion of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), thereby alleviating chronic inflammatory responses in the kidneys.
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At the gut microbiota level, AKK significantly alters the intestinal microbial structure of db/db mice, increasing species richness and diversity. It also regulates the abundance of specific gut microbes associated with renal function and glucose-lipid metabolism, reversing diabetes-induced gut microbiota dysbiosis.
“Next-Generation Probiotic” Akkermansia muciniphila
Akkermansia muciniphila (Akk) is a Gram-negative anaerobic bacterium that colonizes the intestinal mucus layer and plays an important role in maintaining the intestinal barrier, mucus production, and mucus layer thickness. Akk belongs to the phylum Verrucomicrobia and the genus Akkermansia. It is also one of the relatively abundant mucin-degrading bacteria in the human gut, accounting for approximately 0.5%–5.0% of the total intestinal bacterial population. Its optimal growth temperature is 37 °C and its optimal pH is 6.5.
Current research indicates that Akk is closely associated with multiple diseases and shows negative correlations with conditions such as inflammatory bowel disease, amyotrophic lateral sclerosis, hypertension, and diabetes. Due to its unique physiological and metabolic characteristics and probiotic functions, Akk demonstrates diverse biological activities in regulating host health and has become a highly promising next-generation probiotic.
1) Regulation of the Intestinal Barrier
The intestinal barrier regulatory capacity of Akk mainly derives from its colonization in the intestinal mucus layer and its mucin-degrading metabolic characteristics. This bacterium can break down mucin to provide energy for intestinal epithelial cells, promoting intestinal mucosal renewal and mucus secretion while maintaining mucus layer thickness. At the same time, it supplies nutrients to other gut microbes to stabilize microbial structure and reduce the invasion of pathogens and toxic substances, thereby repairing intestinal barrier damage, lowering intestinal permeability, and alleviating various intestinal diseases associated with barrier dysfunction.
2) Improvement of Metabolic Disorders
Studies have shown that both live and pasteurized Akk can reduce body weight and fat mass gain induced by a high-fat diet. This occurs through upregulation of the endogenous cannabinoid 2-AG and downregulation of the lipid droplet regulatory factor perilipin2, which reduces energy absorption. In addition, Akk can improve insulin resistance by lowering β-muricholic acid levels and enhancing FGF15/19 expression to stimulate insulin secretion. It can also reduce oxidative damage, improve liver function, and alleviate glucose and lipid metabolic disorders associated with diabetes and obesity.
3) Neuroprotective Effects
The neuroprotective effects of Akk mainly arise from its regulation of the gut–brain axis and the mediating effects of its metabolites. Studies have shown that Akk can restore neuronal development and synaptic plasticity impaired by a high-fat diet, reduce hypothalamic inflammation, and improve cognitive deficits. The metabolite nicotinamide produced by Akk can enter the central nervous system through the bloodstream, protect motor neurons, and delay the progression of amyotrophic lateral sclerosis. At the same time, Akk supplementation can reduce TNF-α levels in mice, weaken autism-related behaviors, and improve neurodevelopmental disorders caused by increased intestinal permeability.
4) Regulation of Inflammatory Responses
Specific components of Akk and its derived extracellular vesicles also possess anti-inflammatory activity. The outer membrane protein Amuc_1100 from Akk can reduce intestinal infiltration of macrophages and CD8+ cytotoxic T lymphocytes, thereby inhibiting the occurrence of colitis-associated tumors. Extracellular vesicles derived from Akk can enhance colon stability in colitis mouse models and reduce inflammatory cell infiltration. In addition, this bacterium can suppress gene expression of pro-inflammatory cytokines such as IFN-γ, TNF-α, and IL-6 in intestinal epithelial cells. By regulating signaling pathways such as FPR1 and ERK, it promotes mucosal wound repair and exerts anti-inflammatory effects on inflammatory bowel disease and irritable bowel syndrome.
Market Prospects of Akkermansia muciniphila
Akkermansia muciniphila is the first microorganism to translate the scientific concept of “microbiota regulation–metabolic control” into a perceivable consumer experience. Due to its stable colonization, broad biological effects, and retained functionality even after inactivation, Akk demonstrates significant advantages in the development of innovative probiotic products. It is currently driving a new wave of innovation in the global probiotic food industry, with its market size experiencing rapid growth.
According to authoritative statistics and forecasts from QYResearch, the global market size of Akk exceeded USD 320 million in 2024 and is expected to surpass USD 638 million by 2031. Its applications are mainly concentrated in functional foods, foods for special medical purposes, and high-end dietary supplements, with functional foods accounting for 55% of the application share. Data Bridge Market Research predicts that the global gut health supplement market will achieve a compound annual growth rate (CAGR) of 8.5% between 2023 and 2029, while the Chinese market is expected to grow at 28.7%, mainly driven by functional foods and foods for special medical purposes.
Currently, multiple biopharmaceutical companies and research institutions are investing heavily in Akk research. According to the QYResearch 2025 report, the top five global probiotic strain companies collectively account for more than 50% of the market share, with major players including DuPont, Chr. Hansen, DSM-Firmenich, Lallemand, and IFF. These companies dominate the high-end probiotic strain market, including functional strains, pharmaceutical-grade strains, and internationally branded raw material supply.