NAD⁺ Metabolic Reprogramming: A New Therapeutic Avenue for Colorectal Cancer and Colitis
When we talk about health, the gut is often at the center of the discussion. It is not only responsible for digestion and nutrient absorption, but also represents the largest immune organ in the human body. In recent years, however, the incidence of intestinal diseases such as colorectal cancer and colitis has continued to rise. Conventional treatments frequently face challenges including limited targeting precision and significant side effects, highlighting an urgent need for novel therapeutic strategies.
Recently, a joint research team from Beijing Normal University and the Academy of Military Medical Sciences published a landmark study in the internationally renowned journal Advanced Science. This study systematically revealed, for the first time, how an NAD⁺-dependent enzyme in intestinal epithelial cells—SIRT3—regulates local intestinal immune balance through modulation of NAD⁺ metabolism, opening up new directions for the precision treatment of colorectal cancer and colitis.
Engine of energy metabolism: As a key coenzyme in the cellular respiratory chain, NAD⁺ converts sugars and fats from food into usable cellular energy, serving as a natural “power bank” that keeps the body functioning.
Guardian of DNA repair: Cellular DNA is constantly exposed to damage from free radicals and external stressors. NAD⁺ activates specialized repair enzymes that promptly fix damaged genes, reducing disease risks caused by genetic mutations.
Core regulator of immunity: NAD⁺ directly regulates the differentiation and activity of immune cells, enabling the body to accurately identify and eliminate pathogens and tumor cells while maintaining immune homeostasis.
Key modulator of aging: NAD⁺ levels naturally decline with age, which is one of the major drivers of cellular aging and organ functional deterioration.
In the intestine, the role of NAD⁺ is particularly critical. It not only ensures the normal metabolism and renewal of intestinal epithelial cells, but also strengthens the “protective wall” of the intestinal mucosal barrier against harmful bacteria and toxins. At the same time, it precisely regulates local immune responses, acting as an invisible guardian of gut health.
When intestinal inflammation or tumors occur, SIRT3 expression in IECs is significantly upregulated, leading to a reduction in intracellular NAD⁺ levels and suppression of the pro-inflammatory cytokine IL-1β. As a result, immune cells “lose the signal” and fail to mount an effective defense.
Conversely, when SIRT3 function is deficient, the intestine activates a “self-rescue mechanism,” rapidly replenishing NAD⁺ through alternative metabolic pathways. This activates immune responses, effectively restricting colorectal tumor growth while enhancing resistance to bacterial infections.
As the first line of defense of the intestinal barrier, epithelial cell function depends on sufficient NAD⁺ supply.
When NAD⁺ levels are adequate, intestinal epithelial cells secrete pro-inflammatory factors such as IL-1β, which specifically activate the IL-1R1 receptor on T cells.
Receptor activation promotes the differentiation of IFN-γ–producing CD4⁺ T helper 1 (T_H1) cells and cytotoxic T lymphocytes (CTLs). These immune cells are the main forces responsible for eliminating tumor cells and combating infections.
This ultimately forms a complete regulatory chain:
Intestinal epithelial cells → NAD⁺ → IL-1β → T cell activation.
The study demonstrated that SIRT3 deficiency suppresses colorectal cancer growth precisely because it enhances this regulatory axis by elevating NAD⁺ levels, enabling immune cells to accurately target tumor cells. In contrast, SIRT3 overexpression disrupts this pathway, allowing tumor cells to evade immune surveillance and preventing effective control of inflammation.
Gut microbes produce a metabolite known as 3-hydroxyanthranilic acid (3-HA).
After entering intestinal epithelial cells, 3-HA is converted into quinolinic acid (QA).
QA serves as an efficient precursor for NAD⁺ synthesis, enabling rapid NAD⁺ production via compensatory pathways in the absence of SIRT3 and providing sufficient “energy” for immune regulation.
When researchers eliminated gut microbiota using antibiotics, the NAD⁺ elevation and tumor-suppressive effects associated with SIRT3 deficiency were significantly weakened, directly confirming the crucial role of gut microbiota in NAD⁺ metabolic reprogramming.
Through rigorous animal experiments, cellular studies, and clinical data analyses, the joint research team from Beijing Normal University and the Academy of Military Medical Sciences clearly elucidated the regulatory mechanisms of NAD⁺ metabolism in colorectal cancer and colitis. The key findings can be summarized as “one switch, one pathway, and one collaboration.”
When intestinal inflammation or tumors occur, SIRT3 expression in IECs is significantly upregulated, leading to a reduction in intracellular NAD⁺ levels and suppression of the pro-inflammatory cytokine IL-1β. As a result, immune cells “lose the signal” and fail to mount an effective defense.
Conversely, when SIRT3 function is deficient, the intestine activates a “self-rescue mechanism,” rapidly replenishing NAD⁺ through alternative metabolic pathways. This activates immune responses, effectively restricting colorectal tumor growth while enhancing resistance to bacterial infections.
As the first line of defense of the intestinal barrier, epithelial cell function depends on sufficient NAD⁺ supply.
When NAD⁺ levels are adequate, intestinal epithelial cells secrete pro-inflammatory factors such as IL-1β, which specifically activate the IL-1R1 receptor on T cells.
Receptor activation promotes the differentiation of IFN-γ–producing CD4⁺ T helper 1 (T_H1) cells and cytotoxic T lymphocytes (CTLs). These immune cells are the main forces responsible for eliminating tumor cells and combating infections.
This ultimately forms a complete regulatory chain:
Intestinal epithelial cells → NAD⁺ → IL-1β → T cell activation.
The study demonstrated that SIRT3 deficiency suppresses colorectal cancer growth precisely because it enhances this regulatory axis by elevating NAD⁺ levels, enabling immune cells to accurately target tumor cells. In contrast, SIRT3 overexpression disrupts this pathway, allowing tumor cells to evade immune surveillance and preventing effective control of inflammation.
Gut microbes produce a metabolite known as 3-hydroxyanthranilic acid (3-HA).
After entering intestinal epithelial cells, 3-HA is converted into quinolinic acid (QA).
QA serves as an efficient precursor for NAD⁺ synthesis, enabling rapid NAD⁺ production via compensatory pathways in the absence of SIRT3 and providing sufficient “energy” for immune regulation.
When researchers eliminated gut microbiota using antibiotics, the NAD⁺ elevation and tumor-suppressive effects associated with SIRT3 deficiency were significantly weakened, directly confirming the crucial role of gut microbiota in NAD⁺ metabolic reprogramming.
Based on these groundbreaking findings, targeting NAD⁺ metabolic reprogramming has emerged as a promising new strategy for the treatment of colorectal cancer and colitis. Potential future interventions include:
Regulating gut microbiota: Optimizing gut microbiota composition through probiotic interventions to increase 3-HA production, supply sufficient raw materials for NAD⁺ synthesis, and improve the intestinal metabolic environment at its source.
These strategies overcome the limitations of traditional symptom-focused treatments and instead address disease mechanisms at the fundamental levels of cellular metabolism and immune regulation, offering new possibilities for precision therapy of intestinal diseases.
As a national-level “Little Giant” enterprise specializing in biotechnology, Bontac Bio has long focused on the NAD⁺ field and is a pioneer in the NMN industry. Leveraging world-leading biocatalytic technologies and China’s first—and Guangdong Province’s only—provincial coenzyme engineering technology research center, Bontac Bio provides high-purity, high-activity NAD⁺ precursor ingredients.
Looking ahead, Bontac Bio will continue to closely follow scientific advances in NAD⁺ metabolism, drive continuous technological innovation, and fully unlock the health potential of this “molecule of life,” bringing new hope to patients with intestinal diseases.
Gut health is the foundation of overall health. The discovery of NAD⁺ metabolic reprogramming has deepened our understanding of intestinal disease treatment. From basic research to clinical application, Bontac Bio remains committed to professionalism and scientific rigor, supporting progress in biomedical science and safeguarding public health.
Recently, a joint research team from Beijing Normal University and the Academy of Military Medical Sciences published a landmark study in the internationally renowned journal Advanced Science. This study systematically revealed, for the first time, how an NAD⁺-dependent enzyme in intestinal epithelial cells—SIRT3—regulates local intestinal immune balance through modulation of NAD⁺ metabolism, opening up new directions for the precision treatment of colorectal cancer and colitis.
PART 01
NAD⁺: The “All-Purpose Vital Factor” of Human Cells
Many people may still be unfamiliar with NAD⁺, yet it has long been deeply involved in nearly every core physiological process in the human body and can be regarded as an “all-rounder” within cells:Engine of energy metabolism: As a key coenzyme in the cellular respiratory chain, NAD⁺ converts sugars and fats from food into usable cellular energy, serving as a natural “power bank” that keeps the body functioning.
Guardian of DNA repair: Cellular DNA is constantly exposed to damage from free radicals and external stressors. NAD⁺ activates specialized repair enzymes that promptly fix damaged genes, reducing disease risks caused by genetic mutations.
Core regulator of immunity: NAD⁺ directly regulates the differentiation and activity of immune cells, enabling the body to accurately identify and eliminate pathogens and tumor cells while maintaining immune homeostasis.
Key modulator of aging: NAD⁺ levels naturally decline with age, which is one of the major drivers of cellular aging and organ functional deterioration.
In the intestine, the role of NAD⁺ is particularly critical. It not only ensures the normal metabolism and renewal of intestinal epithelial cells, but also strengthens the “protective wall” of the intestinal mucosal barrier against harmful bacteria and toxins. At the same time, it precisely regulates local immune responses, acting as an invisible guardian of gut health.
PART 02
A Scientific Breakthrough: The Central Link Between NAD⁺ Metabolic Reprogramming and Intestinal Diseases
Through rigorous animal experiments, cellular studies, and clinical data analyses, the joint research team from Beijing Normal University and the Academy of Military Medical Sciences clearly elucidated the regulatory mechanisms of NAD⁺ metabolism in colorectal cancer and colitis. The key findings can be summarized as “one switch, one pathway, and one collaboration.”(1) The Key Switch: Bidirectional Regulation of NAD⁺ by SIRT3
The study found that intestinal epithelial cells (IECs) express an enzyme called SIRT3, which acts as a “core switch” in NAD⁺ metabolism and is closely associated with the progression of colorectal cancer and colitis:When intestinal inflammation or tumors occur, SIRT3 expression in IECs is significantly upregulated, leading to a reduction in intracellular NAD⁺ levels and suppression of the pro-inflammatory cytokine IL-1β. As a result, immune cells “lose the signal” and fail to mount an effective defense.
Conversely, when SIRT3 function is deficient, the intestine activates a “self-rescue mechanism,” rapidly replenishing NAD⁺ through alternative metabolic pathways. This activates immune responses, effectively restricting colorectal tumor growth while enhancing resistance to bacterial infections.
Importantly, analysis of the TCGA (The Cancer Genome Atlas) database showed that colorectal cancer patients with high SIRT3 expression in intestinal epithelial cells had significantly lower survival rates, further confirming the critical role of the SIRT3–NAD⁺ pathway in disease progression.
(2) The Core Pathway: The IEC–NAD⁺–T Cell Immune Regulatory Axis
Immune balance lies at the heart of intestinal health, and NAD⁺ serves as the key “signaling bridge” between intestinal epithelial cells and immune cells:As the first line of defense of the intestinal barrier, epithelial cell function depends on sufficient NAD⁺ supply.
When NAD⁺ levels are adequate, intestinal epithelial cells secrete pro-inflammatory factors such as IL-1β, which specifically activate the IL-1R1 receptor on T cells.
Receptor activation promotes the differentiation of IFN-γ–producing CD4⁺ T helper 1 (T_H1) cells and cytotoxic T lymphocytes (CTLs). These immune cells are the main forces responsible for eliminating tumor cells and combating infections.
This ultimately forms a complete regulatory chain:
Intestinal epithelial cells → NAD⁺ → IL-1β → T cell activation.
The study demonstrated that SIRT3 deficiency suppresses colorectal cancer growth precisely because it enhances this regulatory axis by elevating NAD⁺ levels, enabling immune cells to accurately target tumor cells. In contrast, SIRT3 overexpression disrupts this pathway, allowing tumor cells to evade immune surveillance and preventing effective control of inflammation.
(3) An Essential Collaboration: Gut Microbiota Contribute to NAD⁺ Synthesis
Remarkably, NAD⁺ metabolic reprogramming is not a solo effort by intestinal epithelial cells. The gut microbiota play an indispensable supporting role:Gut microbes produce a metabolite known as 3-hydroxyanthranilic acid (3-HA).
After entering intestinal epithelial cells, 3-HA is converted into quinolinic acid (QA).
QA serves as an efficient precursor for NAD⁺ synthesis, enabling rapid NAD⁺ production via compensatory pathways in the absence of SIRT3 and providing sufficient “energy” for immune regulation.
When researchers eliminated gut microbiota using antibiotics, the NAD⁺ elevation and tumor-suppressive effects associated with SIRT3 deficiency were significantly weakened, directly confirming the crucial role of gut microbiota in NAD⁺ metabolic reprogramming.
PART 02
A Scientific Breakthrough: The Central Link Between NAD⁺ Metabolic Reprogramming and Intestinal Diseases
Through rigorous animal experiments, cellular studies, and clinical data analyses, the joint research team from Beijing Normal University and the Academy of Military Medical Sciences clearly elucidated the regulatory mechanisms of NAD⁺ metabolism in colorectal cancer and colitis. The key findings can be summarized as “one switch, one pathway, and one collaboration.”
(1) The Key Switch: Bidirectional Regulation of NAD⁺ by SIRT3
The study found that intestinal epithelial cells (IECs) express an enzyme called SIRT3, which acts as a “core switch” in NAD⁺ metabolism and is closely associated with the progression of colorectal cancer and colitis:When intestinal inflammation or tumors occur, SIRT3 expression in IECs is significantly upregulated, leading to a reduction in intracellular NAD⁺ levels and suppression of the pro-inflammatory cytokine IL-1β. As a result, immune cells “lose the signal” and fail to mount an effective defense.
Conversely, when SIRT3 function is deficient, the intestine activates a “self-rescue mechanism,” rapidly replenishing NAD⁺ through alternative metabolic pathways. This activates immune responses, effectively restricting colorectal tumor growth while enhancing resistance to bacterial infections.
Importantly, analysis of the TCGA (The Cancer Genome Atlas) database showed that colorectal cancer patients with high SIRT3 expression in intestinal epithelial cells had significantly lower survival rates, further confirming the critical role of the SIRT3–NAD⁺ pathway in disease progression.
(2) The Core Pathway: The IEC–NAD⁺–T Cell Immune Regulatory Axis
Immune balance lies at the heart of intestinal health, and NAD⁺ serves as the key “signaling bridge” between intestinal epithelial cells and immune cells:As the first line of defense of the intestinal barrier, epithelial cell function depends on sufficient NAD⁺ supply.
When NAD⁺ levels are adequate, intestinal epithelial cells secrete pro-inflammatory factors such as IL-1β, which specifically activate the IL-1R1 receptor on T cells.
Receptor activation promotes the differentiation of IFN-γ–producing CD4⁺ T helper 1 (T_H1) cells and cytotoxic T lymphocytes (CTLs). These immune cells are the main forces responsible for eliminating tumor cells and combating infections.
This ultimately forms a complete regulatory chain:
Intestinal epithelial cells → NAD⁺ → IL-1β → T cell activation.
The study demonstrated that SIRT3 deficiency suppresses colorectal cancer growth precisely because it enhances this regulatory axis by elevating NAD⁺ levels, enabling immune cells to accurately target tumor cells. In contrast, SIRT3 overexpression disrupts this pathway, allowing tumor cells to evade immune surveillance and preventing effective control of inflammation.
(3) An Essential Collaboration: Gut Microbiota Contribute to NAD⁺ Synthesis
Remarkably, NAD⁺ metabolic reprogramming is not a solo effort by intestinal epithelial cells. The gut microbiota play an indispensable supporting role:Gut microbes produce a metabolite known as 3-hydroxyanthranilic acid (3-HA).
After entering intestinal epithelial cells, 3-HA is converted into quinolinic acid (QA).
QA serves as an efficient precursor for NAD⁺ synthesis, enabling rapid NAD⁺ production via compensatory pathways in the absence of SIRT3 and providing sufficient “energy” for immune regulation.
When researchers eliminated gut microbiota using antibiotics, the NAD⁺ elevation and tumor-suppressive effects associated with SIRT3 deficiency were significantly weakened, directly confirming the crucial role of gut microbiota in NAD⁺ metabolic reprogramming.
PART 03
New Therapeutic Directions: Targeting NAD⁺ Metabolism for Precision Intervention
Based on these groundbreaking findings, targeting NAD⁺ metabolic reprogramming has emerged as a promising new strategy for the treatment of colorectal cancer and colitis. Potential future interventions include:
Modulating SIRT3 activity: Inhibiting SIRT3 to activate QA-mediated NAD⁺ synthesis pathways, thereby enhancing intestinal immune responses and providing a novel therapeutic target for colorectal cancer.
Supplementing NAD⁺ precursors: Appropriate supplementation with NAD⁺ precursors such as QA or NMN (nicotinamide mononucleotide) to directly increase intracellular NAD⁺ levels in intestinal cells, strengthen the intestinal mucosal barrier, and offer adjunctive treatment options for patients with colitis.Regulating gut microbiota: Optimizing gut microbiota composition through probiotic interventions to increase 3-HA production, supply sufficient raw materials for NAD⁺ synthesis, and improve the intestinal metabolic environment at its source.
These strategies overcome the limitations of traditional symptom-focused treatments and instead address disease mechanisms at the fundamental levels of cellular metabolism and immune regulation, offering new possibilities for precision therapy of intestinal diseases.
PART 04
Bontac Bio: Unlocking the Health Potential of NAD⁺ Through Technology
As a national-level “Little Giant” enterprise specializing in biotechnology, Bontac Bio has long focused on the NAD⁺ field and is a pioneer in the NMN industry. Leveraging world-leading biocatalytic technologies and China’s first—and Guangdong Province’s only—provincial coenzyme engineering technology research center, Bontac Bio provides high-purity, high-activity NAD⁺ precursor ingredients.
Looking ahead, Bontac Bio will continue to closely follow scientific advances in NAD⁺ metabolism, drive continuous technological innovation, and fully unlock the health potential of this “molecule of life,” bringing new hope to patients with intestinal diseases.
Gut health is the foundation of overall health. The discovery of NAD⁺ metabolic reprogramming has deepened our understanding of intestinal disease treatment. From basic research to clinical application, Bontac Bio remains committed to professionalism and scientific rigor, supporting progress in biomedical science and safeguarding public health.
