Spine and Microbiome

How Gut Health Affects Degenerative Disc Disease

Many people are often surprised when realizing how interconnected the body is, and this is no exception for spine patients. Those with degenerative disc disease (DDD) may benefit from further research on how gut health affects this disorder. DDD is a chronic condition, and studies have shown that the disorder has a heavy contribution to lower back pain.1,2 The disease is severely painful for patients and can even impact their daily functions and quality of life.2,3 Moreover, there is minimal research in the field exploring how the gut is connected to the spine, which can contribute unique perspectives to patients struggling with chronic disorders. Studies have shown that modification of traditional treatment strategies is crucial for reducing the painful symptoms of DDD.4 The body’s gut microbiota (GM) communicates with parts of the spine, furthering the need for more research on the gut-spine connection to assist patients suffering from chronic spine disorders. Discoveries in this niche aspect of the field may offer vast improvements in patient quality of life, novel treatment plans, and increased patient-reported outcomes postoperatively.

What is Degenerative Disc Disease?

DDD may be present in different parts of the spine, such as the cervical or lumbar region. However, this condition is more common in those with lower back pain. DDD is fairly common, impacting 20% of adolescents and up to 50% of people aged 50 to 70 years. 2 It is important to note that not all patients with DDD have symptoms. Risk factors for this condition are herniated discs, smoking, high levels of physical labor, little to no physical activity, obesity, etc. 2 Morevoer, genetics is also a risk factor for DDD as mutations in certain genes that encode for matrix molecules may alter the function and processes of the disc attributing to the disease. 2 A study conducted by Sang et al showed around one-third of patients with cervical DDD had anxiety or depression, and those who had severe symptoms were even more susceptible to inferior mental health. 5 Finding ways to alleviate symptoms associated with DDD may have a critical impact on patient mental health and quality of life.

The Role of the Gut Microbiome and Proper Nutrition

The gut microbiome composition shifts throughout one's life based on various factors. Some factors include diet, exposure to the environment, geographical location, drugs and medications taken, and even aging.6 The function of the gut microbiome is to assist in destroying bacteria deemed damaging, monitor the immune system, and support digestion.7 A healthy gut contains anti-inflammatory microbes and maintains a stabilized microbiome composition.8 On the other hand, studies have shown that gut dysbiosis increases inflammation due to a leaky gut, where lipopolysaccharides are diffused into circulation.8 Moreover, nutritional disorders can also impact patients who have DDD, which can be viewed in relation to the aspects of the gut. Since the intervertebral discs are avascular, proper diffusion needs to occur with nutrients and gases passing through the matrix to reach the cells.2 If there are nutritional disorders, this diffusion may not occur appropriately and can lead to degenerative diseases, which would make a patient more susceptible if they also have poor gut health.

Li et al hypothesized the mechanisms by which the gut microbiota can cause intervertebral disc disease, such as the transfer of bacteria across the epithelial barrier of the gut into the intervertebral disc and the irregular production of pro-inf lammatory factors by intervertebral disc cells and immune cells.9 Intervertebral discs are protected by a barrier to keep out bacteria, which can induce inflammatory processes. However, this barrier around intervertebral discs can also block immune cells that are critical for recognizing and eliminating harmful elements.9 Due to intestinal inflammation, bacteria can begin to translocate from the epithelial layer of the gut into the intervertebral disc.9 Immune cells may not be able to receive timely feedback from the microenvironment of the disc, resulting in an adverse inflammatory reaction at the disc.9 The body’s reaction to bacterial invasion is the secretion of inflammatory cytokines such as IL-1α/β, IL-17, TNF-α, and IL-6, which can disrupt the matrix of the intervertebral disc by degrading collagen production.9 Essentially, this chain of reactions provokes chemokine production that further deteriorates the extracellular matrix around an intervertebral disc.9 Therefore, DDD arises from the amplification of inf lammatory processes, specifically from the activation of macrophages, B cells, T cells, and neutrophils from the damaged intervertebral disc.9

Dietary Intervention for a Healthy Gut and Spine

Considering the effects of gut dysbiosis resulting in DDD, it is imperative to maintain a healthy gut microbiome. In particular, diet is a major contributor to the composition of the gut microbiome.10 Rinninella et al studied the effects of a typical Western diet, consisting of elevated levels of saturated fats, refined sugars, and processed foods, and found that this diet resulted in increased levels of bacterial species that correlate with dysbiosis and disease, such as Firmicutes. 10 In contrast, a Mediterranean diet based on regular fiber intake consisting of whole grains, vegetables, fruits, and legumes was associated with a lower Firmicutes-to-Bacteroidetes ratio and a higher level of short-chain fatty acids.10 These findings are particularly relevant for individuals with back pain and degenerative disc conditions, as short-chain fatty acids promote the differentiation of primary CD4++ cells into regulatory T cells that play a role in regulating inflammation.11 Regulatory T cells suppress extreme immune responses to prevent chronic inflammation, which can result in DDD. In particular, regulatory T cells are essential in bone formation as they are located on the endosteal surface and promote osteoblast differentiation while inhibiting osteoclast formation.11 Additionally, bone formation is controlled by regulatory T cells through managing the activity of the parathyroid hormone, which balances calcium and bone metabolism to stimulate bone formation.11 Therefore, it is important to include short-chain fatty acids in one’s diet to maintain bone health and prevent disc degeneration through a leaky gut permeating bacteria and resulting in inflammatory responses. In a study conducted by Rajasekaran et al, 40 patients with disc degeneration were studied, and it was found that short-chain fatty acid-producing bacteria were significantly lower in these individuals in comparison to the healthy volunteers.12 On the other hand, patients who did have disc degeneration had a decreased Firmicutes-to-Bacteroidetes ratio compared to healthy individuals.12 Therefore, further studies are warranted to determine the impact of balancing gut microbiomes based on whether they have harmful or beneficial properties.

Additionally, Ratna et al illustrated that the administration of probiotics can shift inflammatory molecules, such as interleukin (IL) -1, -2, -4, -6, and tumor necrosis factor alpha (TNF- α) into an anti-inflammatory state, which includes markers such as IL-10 and transforming growth factor-beta (TGF-β).13 This finding demonstrates that taking probiotics can be beneficial to reduce inflammation in the spine and potentially slow intervertebral disc degeneration through non-inflammatory mechanisms.

Future Research and Potential Treatments

Current strides are being made in determining the connection between the gut microbiota and the spine. For instance, Yao et al studied the efficacy of fecal microbiota transplantation in rats.14 Elevated levels of inflammatory markers such as TNF-α and IL-6 were found in rats with intervertebral DDD using an enzyme-linked immunosorbent assay.14 Ultimately, fecal microbiota transplantation was shown to inhibit the elevated levels of inflammatory molecules in the rats with intervertebral DDD while also upregulating collagen II expression and restoring the homeostasis in the gut microbiota to gradually show improvements in the mice with degenerative discs.14 Collagen II expression is crucial to prevent disc degeneration as it is a major component of the extracellular matrix, providing strength and structure.14 The study highlights the efficacy of treatment for mice, and future studies should explore the effect of fecal microbiota implementation in humans.

Conclusion

Ultimately, prior studies connecting the mechanisms of gut health and DDD illustrate that the gut plays a pivotal role in influencing even distant areas of the body. Therefore, it is important to maintain a healthy diet to supplement the gut microbiota with beneficial bacteria and ensure that the microbiome is balanced. The disruption of the delicate balance of the gut microbiota can result in adverse effects, such as the translocation of bacteria across the barrier of the spine to the avascular intervertebral disc, where inflammatory processes occur and contribute to pain. Additionally, it is imperative to maintain healthy short-chain fatty acid levels to regulate inflammation and parathyroid hormone activity. Existing studies have paved the way for forthcoming research that can be valuable to establish personalized probiotic treatment plans for individuals to obtain the microbiota they need to keep their bones healthy. Advancements such as 16S rRNA sequencing to determine commensal levels and fecal microbiota are considerable strides to unveiling the future of treatments starting from the gut to potentially slow the degeneration of disks and reduce the need for surgical intervention.14

References

1. Kirnaz S, Singh S, Capadona C, et al. Innovative biological treatment methods for degenerative disc disease. World Neurosurg. 2022;157:282-299.

2. Kos N, Gradisnik L, Velnar T. A brief review of the degenerative intervertebral disc disease. Med Arch. 2019;73(6):421-424.

3. Battié MC, Joshi AB, Gibbons LE; ISSLS Degenerative Spinal Phenotypes Group. Degenerative disc disease: what is in a Name? Spine (Phila Pa 1976). 2019;44(21):1523-1529.

4. Morimoto T, Kobayashi T, Kakiuchi T, et al. Gut-spine axis: a possible correlation between gut microbiota and spinal degenerative diseases. Front Microbiol. 2023;14:1290858.

5. Sang D, Xiao B, Rong T, et al. Depression and anxiety in cervical degenerative disc disease: who are susceptible? Front Public Health. 2023;10:1002837.

6. Bradley E, Haran J. The human gut microbiome and aging. Gut Microbes. 2024;16(1):2359677.

7. Jandhyala SM, Talukdar R, Subramanyam C, Vuyyuru H, Sasikala M, Nageshwar Reddy D. Role of the normal gut microbiota. World J Gastroenterol. 2015;21(29):8787-8803.

8. Mousa WK, Chehadeh F, Husband S. Microbial dysbiosis in the gut drives systemic autoimmune diseases. Front Immunol. 2022;13:906258.

9. Li W, Lai K, Chopra N, Zheng Z, Das A, Diwan AD. Gut-disc axis: a cause of intervertebral disc degeneration and low back pain? Eur Spine J. 2022;31(4):917-925.

10. Rinninella E, Tohumcu E, Raoul P, et al. The role of diet in shaping human gut microbiota. Best Pract Res Clin Gastroenterol. 2023;62-63:101828.

11. Wang K, Liu X, Huang H, et al. A new target for treating intervertebral disk degeneration: gut microbes. Front Microbiol. 2024;15:1452774.

12. Rajasekaran S, Vasudevan G, Tangavel C, et al. Does the gut microbiome influence disc health and disease? The interplay between dysbiosis, pathobionts, and disc inflammation: a pilot study. Spine J. 2024;24(10):1952-1963.

13. Ratna HVK, Jeyaraman M, Yadav S, Jeyaraman N, Nallakumarasamy A. Is dysbiotic gut the cause of low back pain? Cureus. 2023;15(7):e42496.

14. Yao B, Cai Y, Wang W, et al. The effect of gut microbiota on the progression of intervertebral disc degeneration. Orthop Surg. 2023;15(3):858-867.

Contributors:

Shriya Patel, BS

Sloane Ward, BS

Kern Singh, MD

From the Department of Orthopaedic Surgey at Rush University Medical Center in Chicago, Illinois.