Weekly Wellness Spotlight

Dear Julie,

May 2019….More than 620 registered attendees from 45 states and 11 countries traveled to Destin, Florida for the 2019 Congress of Clinical Rheumatology. One of the highlights was a lecture presented by James T. Rosenbaum, MD on the intestinal microbiome in rheumatic diseases. Dr. Rosenbaum is Chief of Ophthalmology at the Legacy Devers Eye Institute in Portland, Oregon and he is also Chief of Arthritis and Rheumatic diseases at the Oregon Health and Science University.

“I submit to you that in any disease that has an immune component — whether it’s Alzheimer’s, Parkinson’s, autism, atherosclerosis, obesity, diabetes and any disease that you are seeing in your clinics with an immune component — the microbiome is having some effect,” Rosenbaum told the attendees, “Whether it’s a small effect or a large effect, it is hard to say, but in these experimental rodents, it’s a huge effect. And one day, we will have therapy that is directed toward repairing or changing, or altering, that microbiome.”

Microbiome may contribute to all immune-related disease


Although microbiome research is exploding, we are still at the tip of the iceberg in our understanding of how the microbiome influences health and disease. For this week’s wellness spotlight, please see the attached articles on the microbiome that have been recently published.

Can High-Fiber Diet Influence ImmunoTx Response via Microbiome?
“We found that diet and supplements appear to have an effect on a patient’s ability to respond to cancer immunotherapy, most likely due to changes in their gut microbiome,” said Christine Spencer, PhD, of the Parker Institute for Cancer Immunotherapy in San Francisco, reporting at the American Association for Cancer Research annual meeting. “The gut microbiome plays a big role in moderating the immune system, so the idea that we could potentially change the microbiome — whether by diet or other means — to improve response to immunotherapy treatment is really exciting.”

A Review of Traumatic Brain Injury and the Gut Microbiome: Insights into Novel Mechanisms of Secondary Brain Injury and Promising Targets for Neuroprotection
“We believe the relationship between TBI and the gut microbiome represents an area of study that could lead to a wide range of future research in new clinical intervention strategies. Alterations in the gut microbiome could potentially serve as a biomarker to improve detection of TBI and monitor progression or as a therapeutic target to prevent secondary injury in brain-injured patients. Therapeutic strategies such as FMT and probiotics may offer a neuroprotective benefit by targeting the dysregulated gut-microbiota-brain axis and restoring the gut microbiota to a healthier profile. Leveraging knowledge of the gut microbiome in the setting of TBI holds the exciting potential to influence treatment of brain-injured patients and enhance quality-of-life for patients with TBI.”

Marshaling the Microbiome against Obesity, Infection, and Inflammation
“The above article highlights the key findings of several presentations delivered at the 8th annual Gut Microbiota for Health World Summit. While they are just a sampling of presentations delivered, the reader will notice the diversity of topics currently being examined through a microbiota lens including P-glycoprotein expression and function, diet and C. difficile, prebiotics and radiation, and several matters pertaining to obesity.”

What Does the Microbiome Have to Do with Stress and Depression? | UCSF Science of Caring
An important note from this study was that mothers who experienced depression while pregnant had babies that are depleted of certain health-promoting species of bacteria.

Deciphering the Chemical Lexicon of Host–Gut Microbiota Interactions
“The human intestine harbors an immense, diverse, and critical population of bacteria that has effects on numerous aspects of host physiology, immunity, and disease. Emerging evidence suggests that many of the interactions between the host and the gut microbiota are mediated via the microbial metabolome, or the collection of small-molecule metabolites produced by intestinal bacteria. This review summarizes findings from recent work by focusing on different classes of metabolites produced by the gut microbiota and their effects in modulating host health and disease. These metabolites ultimately serve as a form of communication between the gut microbiome and the host, and a better understanding of this chemical language could potentially lead to novel strategies for treating a wide variety of human disorders.”

Butyrate, neuroepigenetics and the gut microbiome: Can a high fiber diet improve brain health?
“As interest in the gut microbiome has grown in recent years, attention has turned to the impact of our diet on our brain. The benefits of a high fiber diet in the colon have been well documented in epidemiological studies, but its potential impact on the brain has largely been understudied. Here, we will review evidence that butyrate, a short-chain fatty acid (SCFA) produced by bacterial fermentation of fiber in the colon, can improve brain health. Butyrate has been extensively studied as a histone deacetylase (HDAC) inhibitor but also functions as a ligand for a subset of G protein-coupled receptors and as an energy metabolite. These diverse modes of action make it well suited for solving the wide array of imbalances frequently encountered in neurological disorders. In this review, we will integrate evidence from the disparate fields of gastroenterology and neuroscience to hypothesize that the metabolism of a high fiber diet in the gut can alter gene expression in the brain to prevent neurodegeneration and promote regeneration.”

Research deepens understanding of gut bacteria’s connections to human health, disease
“While recent research indicates that human health is affected by the gut microbiome, the functional mechanisms that underlie host-microbiome interactions remain poorly resolved. Metagenomic clinical studies can address this problem by revealing specific microbial functions that stratify healthy and diseased individuals. To improve our understanding of the relationship between the gut microbiome and health, we conducted the first integrative functional analysis of nearly 2,000 publicly available fecal metagenomic samples obtained from eight clinical studies. We identified characteristics of the gut microbiome that associate generally with disease, including functional alpha-diversity, beta-diversity, and beta-dispersion. Using regression modeling, we identified specific microbial functions that robustly stratify diseased individuals from healthy controls. Many of these functions overlapped multiple diseases, suggesting a general role in host health, while others were specific to a single disease and may indicate disease-specific etiologies. Our results clarify potential microbiome-mediated mechanisms of disease and reveal features of the microbiome that may be useful for the development of microbiome-based diagnostics.”

Probiotics Improve Inflammation-Associated Sickness Behavior by Altering Communication between the Peripheral Immune System and the Brain
“Patients with systemic inflammatory diseases (e.g., rheumatoid arthritis, inflammatory bowel disease, chronic liver disease) commonly develop debilitating symptoms (i.e., sickness behaviors) that arise from changes in brain function. The microbiota-gut-brain axis alters brain function and probiotic ingestion can influence behavior. However, how probiotics do this remains unclear. We have previously described a novel periphery-to-brain communication pathway in the setting of peripheral organ inflammation whereby monocytes are recruited to the brain in response to systemic TNF-α signaling, leading to microglial activation and subsequently driving sickness behavior development. Therefore, we investigated whether probiotic ingestion (i.e., probiotic mixture VSL#3) alters this periphery-to-brain communication pathway, thereby reducing subsequent sickness behavior development. Using a well characterized mouse model of liver inflammation, we now show that probiotic (VSL#3) treatment attenuates sickness behavior development in mice with liver inflammation without affecting disease severity, gut microbiota composition, or gut permeability. Attenuation of sickness behavior development was associated with reductions in microglial activation and cerebral monocyte infiltration. These events were paralleled by changes in markers of systemic immune activation, including decreased circulating TNF-α levels. Our observations highlight a novel pathway through which probiotics mediate cerebral changes and alter behavior. These findings allow for the potential development of novel therapeutic interventions targeted at the gut microbiome to treat inflammation-associated sickness behaviors in patients with systemic inflammatory diseases.”

SIGNIFICANCE STATEMENT “This research shows that probiotics, when eaten, can improve the abnormal behaviors (including social withdrawal and immobility) that are commonly associated with inflammation. Probiotics are able to cause this effect within the body by changing how the immune system signals the brain to alter brain function. These findings broaden our understanding of how probiotics may beneficially affect brain function in the context of inflammation occurring within the body and may open potential new therapeutic alternatives for the treatment of these alterations in behavior that can greatly affect patient quality of life.”