Title: Does occult infection account for disc degeneration with type 1 Modic change in the lumbar spine?
Funder: Versus Arthritis

Abstract: Intervertebral disc degeneration (DD) is an age-related phenomenon and a major risk factor for low back pain (LBP). LBP is a major global issue, rising inexorably up the Lancet global ranking of causes of disability. While degenerative conditions are not generally considered to be caused by infection, there is some evidence that some forms of DD are caused by low grade infection of the spine. Previous studies have examined surgical samples of degenerate disc taken at operation and some suggested bacteria were present, particularly those normally found on the skin, while other studies failed to find bacteria. Some argue that bacteria are not detectable if scrupulous collection techniques which avoid contamination are used. We are a consortium of experts in DD (SR), LBP and DD genetics (FW) and microbiome studies (JM) with decades of track record in our respective fields. Newly available techniques to detect bacterial DNA use gene sequencing methods and provide alternatives and agnostic methods to traditional microbiology in which certain families of bacteria may be ‘cultured’ on a plate, methods having inherent shortcomings. The spine is composed of vertebral bodies with discs in between, separated by the bony endplate. Our recent work shows endplate damage arises early in the degenerative process and is probably the trigger for disc degeneration, and for the vertebral body inflammation called ‘Modic change’ which is visible on spine MR scan. It is postulated that damage to the endplate makes it ‘leaky’. The disc normally receives oxygen and nutrients by diffusion because it is avascular. In DD new blood vessels are seen to grow in, which may provide microbes in the blood-borne bacteria with a route to settle in the immune-privileged disc. Body sites conventionally considered sterile (eg. renal tract) or indeed the gut lying against the spine may contribute microbes causing Modic change. The hypothesis is that the inflammatory Modic change (type 1) is caused by bacteria from elsewhere in the body. In this case-control study we will collect surgical samples and compare bacterial DNA from bacteria in discs having adjacent type 1 Modic change (cases) to discs without Modic change (controls). We will investigate whether bacterial DNA identified in the spine is also evident in other systems by collecting pre-operatively urine, saliva, faeces, skin swabs and blood. The project aims to identify the bacteria(-um) responsible for Modic type 1 change and locate its site of origin in the body. In addition we will examine serum collected pre-operatively for evidence of a low grade inflammatory response. Any bacteria identified will further undergo culture and sensitivity to antibiotics testing. Thus we will demonstrate not only if bacterial DNA is present in DD, but additionally if inflammation is present and potentially identify the bacteria in other anatomical sites suggesting a source. Results from this work will inform future randomised controlled clinical trials of appropriate antibiotics or demonstrate clearly that this is not something that should be attempted, or not, thereby reducing the burden of antibiotic resistance - another issue of global importance.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INFLAMMATORY AND IMMUNE SYSTEM;MUSCULOSKELETAL