A few weeks ago, I had the opportunity to attend Digestive Disease Week in San Diego, California! DDW is the largest international meeting on digestive health and gastroenterology, and it was great to take a break from writing my dissertation to learn about the latest cutting-edge research in SIBO, IBS, GERD, IBD, the gut microbiome, and more!
This was my first year attending DDW, and it was so nice to meet some of the top researchers and gastroenterologists in the country and see that the microbiome is finally getting the attention it deserves in GI diseases. In fact, there was so much interest in the microbiome talks that several of them were overflowing into the hallways of the conference center!
Many of you told me how much you liked my previous conference write-ups, so I thought I would share some of my highlights from the four-day conference.
1) Individuals with SIBO may in fact have small intestinal dysbiosis
Dr. Gabriela Leite from Cedars-Sinai kicked off the conference by presenting a recent study that attempted to characterize the small intestinal microbiota in individuals with small intestinal bacterial overgrowth (SIBO). Unfortunately, the participants in the study were diagnosed with SIBO based on culture-based criteria, which as I discussed in a recent article, is outdated and unreliable. The research group concluded that patients with SIBO have a distinct small intestinal microbiome characterized by low microbial diversity and a high abundance of Proteobacteria. However, I think the more appropriate conclusion would be hat individuals with dysbiosis characterized by high Proteobacteria will simply appear to have bacterial overgrowth by culture methods that select for facultative anaerobes. A study published in Nature Communications in early May 2019 seems to confirm this notion – that culture simply selects for the growth of certain bacteria, and that small intestinal dysbiosis is more reliably correlated with symptoms.
2) Butyrate supplements can shift the gut microbiota to increase butyrate-producing bacteria!
Dr. Sonia Facchin from Italy presented a fascinating poster on the effects of encapsulated sodium butyrate supplements on the gut microbiota in patients with IBD. Butyrate is a short-chain fatty acid (SCFA) produced in the gut from the fermentation of dietary fiber and is well-known to be anti-inflammatory and help maintain gut barrier function. Many people have argued that butyrate supplementation is equivalent to a band-aid fix, and that we should be using prebiotics to improve our gut’s own endogenous butyrate production. However, this new prospective, randomized, placebo-controlled study suggests that 1800 milligrams per day of butyrate can not only reduce inflammation and improve quality of life, but can also act like a prebiotic, increasing the number of butyrate-producing bacteria in IBD patients! This may be due to the reduction in inflammation, cross-feeding interactions with other SCFA-producers, or direct antimicrobial effects against bacteria that do not produce SCFAs. Regardless of the mechanism, I certainly look forward to a lot more study in this area.
3) Integrative care that includes diet therapy maximizes outcomes in IBS
Dr. William Chey, a gastroenterologist from the University of Michigan, gave an excellent summary of the current evidence of dietary therapies for IBS. He emphasized that, much like IBS in general, non-celiac wheat sensitivity is a heterogeneous group of patients. While some individuals react to gluten itself, other patients may be reacting to fructan or other components in wheat. For yet another subset of patients, customized elimination diets may be beneficial. Still, the greatest weight of the evidence supports the low FODMAP diet, with about half of patients seeing improvements in pain, bloating, and disease-related quality of life. Dr. Chey stressed, however, that the low FODMAP diet should not be utilized as a long-term treatment and should be personalized to allow diversification of the diet. He also highlighted several studies indicating that prebiotics or glutamine could improve symptoms, and closed his talk by emphasizing that “holistic, integrative care maximizes outcomes in IBS patients” and that the “pieces will fit together differently for each patient.” I couldn’t have said it better myself
4) Dietary therapies are also crucial in inflammatory bowel disease
Dr. James Lewis from the University of Pennsylvania followed with a summary of the evidence for dietary therapy in IBD. He primarily focused on the utilization of liquid nutritional formulas, including partial or exclusive enteral nutrition used in hospitals, but also covered the Crohn’s disease exclusion diet, the CD-TREAT diet, and the Specific Carbohydrate Diet (SCD), all of which have shown clinical efficacy in Crohn’s disease. I would have added that many patients with ulcerative colitis or Crohn’s disease may also benefit from the autoimmune protocol (AIP) diet. In a 2016 pilot study of AIP for IBD, 73 percent of the participants achieved clinical remission in just six weeks. In some IBD patients, a ketogenic diet or short-term fasting may be helpful, as beta-hydroxybutyrate may help to overcome poor butyrate uptake in the inflamed mucosa.
5) Short-term 24-hour fasting boosts Akkermansia muciniphila and helps restore the gut barrier
Dr. Suzanne Devkota from Cedars Sinai Medical Center gave an excellent talk about the role of diet, seasonality, and fasting in shaping the gut microbiome. Seasonality plays a large role in shaping gut microbiome composition among hunter-gatherers, but this seasonal cycling and its associated microbial diversity has largely been lost in Western populations. Continuous access to food, the higher energy density of Western foods, and the move away from native diets have led to a shifting microbial landscape. So, could nutrient deprivation be a part of the cure? Recent studies in Dr. Devkota’s lab have sought to determine the potential benefits of short-term fasting on this altered landscape. In mice, a single 24-hour fast resulted in an expansion of Akkermansia muciniphila and significantly reduced inflammation. In a pilot human study, fasting also promoted a bloom of A. muciniphila and suppressed abundance of Proteobacteria, a phylum that has been associated with inflammation and dysbiosis. Their next step will be to try this in patients with IBD, to see if fasting can have benefits for the gut microbiome and gut barrier function in this population.
6) Bacterial production of histamine is key in irritable bowel syndrome
Dr. Premysl Bercik from McMaster University presented some fascinating data on host-microbe interactions related to histamine and IBS. Previous studies have shown that improvement in IBS symptoms on a low FODMAP diet is associated with certain gut microbiota profiles and a decrease in urine histamine levels after the dietary intervention. In a recent study, Dr. Bercik’s lab colonized germ-free mice with the gut microbiome from a healthy control, an IBS patient with low urine histamine (IBS-LH), and an IBS patient with high urine histamine (IBS-HH). After a colonization period, they put these three groups of “humanized” mice on a low or high FODMAP diet. Incredibly, they found that the high fermentable diet altered GI transit, gut permeability, and visceral sensitivity only in mice that had received the “high-histamine” microbiota. This suggests that gut symptoms triggered by FODMAPs in patients with IBS are caused by low-grade gut inflammation and bowel dysfunction, primarily driven by bacterial production of histamine! The group has also identified which bacteria are producing most of the histamine, but were not willing to share until the study is published.
7) Helminths induce fetal reprogramming of the intestinal stem cell niche
Dr. Ophir Kein from the University of California San Francisco spoke about the effects of helminths on the intestinal microenvironment. Infecting billions worldwide, parasitic helminths are often asymptomatic but can cause morbidity or mortality due to malnourishment and anemia. Helminths are also used therapeutically to treat or protect against a number of immune-mediated diseases, including IBD, allergies, asthma, and atopic dermatitis. Using a mouse model of helminth infection, Dr. Kein’s lab was able to study the effects of helminths on the intestinal epithelium near the worm. To their surprise, helminths actually reduced expression of certain genes that are known to be involved in intestinal stem cell proliferation, but instead induced changes in the adult epithelium such that it closely resembled the fetal epithelium. This developmental reprogramming may provide a novel mechanism to help repair mucosal inflammation in adulthood.
(For more on helminths, I recommend the book “The Epidemic of Absence: A New Way of Understanding Allergies and Autoimmune Diseases”)
8) Small intestinal microbes influence the allergenic potential of common dietary proteins
Dr. Elena Verdu presented some fascinating data suggesting that the composition of the small intestinal microbiota may influence the allergenic potential of dietary proteins. One of the most important roles that the gut microbiome plays is aiding in digestion. While our body does produce some protein-degrading enzymes, we rely on bacterial proteases to degrade some of the proteins we consume. Dr. Verdu’s lab has particularly looked at the capacity of different microbes to degrade gluten. They found that the opportunistic pathogen Pseudomonas aeruginosa can break down gluten into large, highly immunogenic peptides. However, if Lactobacillus is also present, it may “detoxify” these peptides, preventing the inflammatory immune response! In other words, gluten sensitivity may in fact be dysbiosis of the small intestine, characterized by high levels of opportunistic pathogens and low levels of protective microbes like Lactobacillus.
9) Evolutionary perspectives bring new insight to FUT2, Faecalibacterium, and gut dysbiosis as risk factors in IBD.
Dr. John Baines from the Precision Medicine in Chronic Inflammation Center in Germany stressed the importance of looking at genetic and microbial risk factors for IBD from an evolutionary perspective. For instance, while FUT2 “non-secretors” have greater protection against norovirus, they also have reduced Bifidobacterium and increased susceptibility to Crohn’s disease, an example of balancing selection in action. Facealibacterium prausnitzii also presents an interesting paradox. Low F. prausnitzii is a universal characteristic of Crohn’s disease in Western populations, yet Malawian and Venezualan populations have very low abundance of this bacterium with low rates of IBD. Dr. Baines suggested that we may be co-evolving a greater dependency on F. prausnitzii in lieu of ancestral diversity. Lastly, we need to consider the evolution of microbes within hosts. The majority of studies have focused on the changes in number and relative proportions of taxa during IBD, but we know little about the nature of bacterial evolution and adaptation to the inflamed gut over the course of the disease. Overall, this kind of evolutionary thinking is what we need to generate new research directions and better understand the long-term dynamics of the gut ecosystem!
10) Mitochondrial dysfunction drives intestinal inflammation in the ileum due to Paneth cell abnormalities.
Dr. Arianne Theiss spoke about how mitochondrial dysfunction can contribute to or even cause intestinal inflammation. Several studies have now shown that mitochondrial DNA can be found in the plasma of IBD patients, a sign of mitochondrial damage and an activator of the immune system. Dr. Theiss’s lab has particularly focused on a protein called PHB1 (prohibitin 1) that is downregulated in IBD patients but is central to mitochondrial function. Through a series of experiments, they determined that PHB1 deficiency and the subsequent mitochondrial dysfunction particularly affects Paneth cells, which are essential for mucosal defense and the maintenance of a healthy intestinal stem cell niche. Paneth cell abnormalities are shortly followed by inflammation in the terminal ileum, the region most commonly associated with Crohn’s disease. This suggests that mitochondrial targeted therapeutics could potentially have benefits for Crohn’s
11) Host-fungi interactions in inflammatory bowel disease
Dr. Iliyan Iliev of Cornell presented on the role of fungi, or the “mycobiota” in IBD. IBD patients tend to have a reduction in fungal diversity and an overgrowth of Candida species. Moreover, greater than 50 percent of Crohn’s disease patients have antifungal antibodies. Dr. Iliev’s lab has identified certain host genetic polymorphisms in the CX3CR1 gene that can result in defective antifungal responses. Genetic ablation of particular immune cells that should normally express this receptor in mice led to changes in gut fungal communities and severe colitis. Treating the mice with antifungals was shown to ameliorate this chronic inflammation, suggesting that there may be ways of overcoming this genetic predisposition. Future studies in the Iliev lab seek to understand how the gut mycobiota might impact the response of patients with UC to fecal microbiota transplant.
12) A new way to sample the small intestinal microbiome
Dr. Gang Wang introduced a new autonomous and minimally-invasive device for sampling the gut microbiome. Due to the relative inaccessibility of the small intestine, this region of the GI tract has been poorly characterized, despite the fact that the small intestinal microbiome has a major impact on health and disease. Dr. Wang’s lab has recently developed what they call an Intestine microbiome aspiration (IMBA) capsule, which is ingested and can collect a sample specifically from the small intestine. The capsule is then excreted and sent back to the lab for analysis. Pilot human studies have already demonstrated the safety and efficacy of this collection method, and it’s likely that we are not too far off from having this in clinical practice!
13) Challenging scientific dogma: the power of persistence
Dr. Balfour Sartor, legendary researcher in the microbiome and IBD, gave an incredibly moving talk describing the challenges and rewards of his research career, and how his lab came to be key in unraveling the pathogenesis of IBD. While the idea that resident bacteria could be triggering inflammation in IBD is now widely accepted, it was initially met with intense scrutiny. Dr. Sartor encouraged anyone with an idea that contradicts current scientific dogma to believe in their message, share their ideas, and know that persistence and hard work will eventually pay off. As someone who tries to bridge the gap between conventional and functional medicine and make my own unbiased interpretation of the evidence, this talk definitely hit home for me.
Favorites in San Diego
I’ve been to San Diego for conferences several times now, and it is definitely one of my favorite cities! Here are a few of the places my husband and I enjoyed during our trip:
Ocean Beach: we got in a day before the conference to get some much-needed sunshine and relax time! We really enjoyed the water and loved watching all of the pelicans here.
Breakfast Republic: amazing breakfast near Ocean Beach. I got the shrimp & ricotta frittata. After so many years avoiding eggs, it’s nice to be able to have breakfast dishes again!
Sunset Cliffs Natural Park: a beautiful cliff-side park and a great place to watch the sunset. We stayed in an Airbnb just a few minutes away and enjoyed the view on our walks to and from the downtown Ocean Beach area.
Lazy Hummingbird Coffee & Tea House: a cute little shop in Ocean Beach where we tried CBD coffee for the first time! It was…interesting. I think I prefer them separate, but Steven loved it.
Meze Greek Fusion: a great stop for lunch not too far from the convention center downtown with open-air seating! I had a really good traditional Greek salad with salmon and feta. (I’m officially obsessed with feta).
Sadaf Restaurant: awesome Persian food and the friendliest staff you’ll ever meet. This is a must visit for me from now on anytime I’m near San Diego. They even have shakers of sumac on the table!
Little Italy Mercato Farmer’s Market: after visiting this awesome market in 2018, I knew I had to go back. We had a lot of fun walking around and got some great mango coconut yogurt.
Balboa Park & Japanese friendship gardens: probably not a surprise that this made my list, but it was my first time visiting this part of San Diego. We really liked the rose and cactus gardens east of Balboa Park!
(For more of my favorite places in San Diego, see my highlights from EB 2018.)
That’s all for now! Hope you enjoyed some of the latest and greatest insights in gut health! For more updates, be sure to subscribe to my newsletter. You can also support my work through Patreon, which helps me to attend conferences like DDW so that I can bring these highlights to you!