The Gut Microbiome: What is it?
The gut microbiome is an entire ecosystem within the gastrointestinal tract and is considered an immune and metabolic organ (Suchodolski 2022). This ecosystem interacts closely with the host and influences host health (Suchodolski 2021). The gut microbiome acts as an organ in the body, that when altered may impact the heath of distant organs and disease processes.
Microbial Diversity Within the Gut
The health of the gut microbiome results from the balance of bacteria, fungi, archaea, viruses, and protozoa (Suchodolski 2021; Pilla and Suchodolski 2018) that reside in the gut. For many reasons, the health of the gut microbiome is primarily measured and assessed through the balance and diversity of the bacteria that reside in the gastrointestinal tract. The bacterial microbiome is altered by factors that are both internal and external to the gut itself and similarly impact the health of the gut and non-gut organs and processes (Amon P, Sanderson I. 2017).
The Gut Microbiome Matters
The gut microbiome is an organ in the body with multiple functions. It contributes to the metabolism and affects the physiologic functions of the host. It plays a role in many processes in the body, such as the metabolism of nutrients as well as immunomodulation (Jandhyala 2015). When the gut microbiome is abnormal, the effects are seen throughout the body and the host can develop a series of symptoms as a consequence. This is a representation of the multitude of functions, and the marked effects, that changes in the population of bacteria within the gastrointestinal tract can have on a host. As with any other organ system, any failure or change in this organ leads to changes in the body.
The Association Between the Gut Microbiome and Gut Health
An alteration in the gut bacteria can be associated with dysfunction of the gastrointestinal tract. These alterations can cause changes in the permeability of the small intestines and their overall function (Suchodolski 2022). An important question to ask is whether alterations in gut bacteria are associated with certain diseases. Dysbiosis, which is an alteration in the gut microbiota, is usually associated with disease. The Dysbiosis Index (DI), a PCR-based algorithm, is used to quantify gastrointestinal dysbiosis. The DI can be used to monitor disease progression and therapeutic response. (Pilla and Suchodolski 2018). Certain types of bacteria have been associated with systemic inflammation, which is often associated with disease (Zongyu, et al 2020).
The Association Between the Gut Microbiome and Cancer
The gut microbiome plays a role in the immune function of the host (Suchodolski 2022; Zongyu, et al 2020). Next-generation sequencing (NGS) has been used for gene profiling and to research microbiota in fecal samples. Fecal samples can be analyzed via NGS to determine the relationships and interactions between hosts and the microbiota, allowing us to determine if there is a link between specific bacterial populations and specific disease processes, such as cancer (Zongyu, et al 2020). Studies have shown that dogs with distinct fecal microbiota profiles as compared to control dogs, had neoplastic disease (Herstad KMV, 2018). For instance, in a 2018 study comparing control dogs to dogs with multicentric lymphoma, the gastrointestinal microbes differed significantly in dogs with multicentric lymphoma as compared to control dogs (Gavazza et al 2018). Studies in mice revealed that the bacteria within the gastrointestinal tract can influence the therapeutic effects of cancer treatment (Zhua, 2020). With the constant addition of new technologies in the field of science and medicine, there is a new tool being used to look at metabolites. Metabolomics is the field that does a comprehensive measurement of all metabolites in a biological specimen (Clish 2015). This is useful because it allows clinicians to look for different biomarkers that may be associated with disease and the response to therapeutics. There is current research being done in this field, including through Ethos Discovery, which is looking at the systemic consequences that occur in patients with intestinal dysbiosis.
Beyond Cancer to Metastases
The process of metastasis in complex and consists of a sequence of events. The gut microbiome’s influence on the immune system can be used as an indirect method of affecting metastasis in cancer patients. This has yet to be proven, but several mechanisms have been proposed, such as whether the gut microbiota themselves, or a metabolite produced by the gut microbiota signal a break in metastatic dormancy (Mallery, K. et al, 2021). There are still many unanswered questions when it comes to cancer metastasis and the influence of the gut microbiota, but hopefully we can start to make progress in this field.
A Clinical Study of the Link Between Altered Gut Health and Cancer Spread in Dogs
Cancer is a multifactorial disease with multiple components that lead to neoplasia and metastasis. The gut microbiome has been associated with a multitude of disease processes in many species, including cancer. However, the association between the microbial population in the gastrointestinal tract and cancer is not so clear cut, and in fact, it is quite complex. Cancer metastasis is affected by the microenvironment of the tumor, as well as systemic factors in the patient. Ethos Discovery has multiple projects relating the gut microbiome and cancer, including a study looking at dogs with appendicular osteosarcoma and the gut microbiome. Preliminary data suggests that there is a difference in the population of the gut bacteria in dogs with metastasis as compared to dogs without metastasis. This study is in the early stages of data collection and evaluation but there appears to be some influence of the bacteria within the gut and the progression of cancer.