1.
Treating the Underlying Causes of Chronic Migraine
As the pioneer and global leader of Functional Medicine, the Institute of Functional Medicine (IFM) leads and catalyses the efforts of a large and expanding Functional Medicine ecosystem, including providers, educators, payers, industry leaders, regulators, and influencers.
2022
Abstract
Pinpointing the exact pathophysiology of migraines is challenging. This insight from the IFM looks at mitochondrial dysfunction, oxidative stress and gastrointestinal disorders as key players in the role of migraine development and progression. Research suggests that the prevalence of migraines can be increased with a number of gastrointestinal conditions such as helicobacter pylori infection, irritable bowel syndrome and coeliac disease. Nutrition interventions that have been shown to improve quality of life in chronic migraine sufferers includes the ketogenic diet and nutrient supplementation with riboflavin, CoQ10 and magnesium.
2.
Crosstalk between the microbiome and epigenome: messages from bugs.
Qin, Y, Wade, PA
Journal of biochemistry. 2018;163(2):105-112
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Plain language summary
Trillions of microbes live symbiotically in and on an individual human being, most of them inside the digestive tract and communally known as the gut microbiome. The gut microbiome plays a vital role in the individual host’s health, not only by helping digest food and harvest energy, but also by regulating immune development and influencing gene expression. Diet and factors, such as infections and the use of antibiotics, can alter the balance of the microbiome and lead to various outcomes. This paper reviewed the current understanding of the ways in which the gut microbiome is capable of altering the host’s gene expression through microbial signals, including metabolites, bile acids, inflammation and altered composition. The studies highlighted in the paper show that gut microbes communicate both with local cells in the intestines and with more distant organs, such as the liver and the cardiovascular system. Through this communication, they can regulate the expression of immune cells, cancer cells, enzymes and inflammation-related molecules. The authors concluded that these interactions, or the crosstalk between the microbes and the host, demonstrate a crucial role of the gut microbiome in the host’s response to environmental signals. However, many of the mechanisms are still unclear, so further studies are needed to explain specific microbe-derived signals, affecting host gene expression, and to deepen our understanding of how lifestyle, health status and environmental exposures, such as antibiotics, regulate the microbiome and its influence.
Abstract
Mammals exist in a complicated symbiotic relationship with their gut microbiome, which is postulated to have broad impacts on host health and disease. As omics-based technologies have matured, the potential mechanisms by which the microbiome affects host physiology are being addressed. The gut microbiome, which provides environmental cues, can modify host cell responses to stimuli through alterations in the host epigenome and, ultimately, gene expression. Increasing evidence highlights microbial generation of bioactive compounds that impact the transcriptional machinery in host cells. Here, we review current understanding of the crosstalk between gut microbiota and the host epigenome, including DNA methylation, histone modification and non-coding RNAs. These studies are providing insights into how the host responds to microbial signalling and are predicted to provide information for the application of precision medicine.
3.
Mucosal microbiome dysbiosis in gastric carcinogenesis.
Coker, OO, Dai, Z, Nie, Y, Zhao, G, Cao, L, Nakatsu, G, Wu, WK, Wong, SH, Chen, Z, Sung, JJY, et al
Gut. 2018;67(6):1024-1032
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Gastric cancer (GC) is the 4th most common cancer and a leading cause of cancer-related deaths worldwide. Infection with Helicobacter pylori is an important risk factor for GC and other changes in gastric microbial composition are thought to play role in gastric carcinogenesis. This observational study aimed to elucidate the microbial changes that are characteristic for the different stages of gastric tumor development. The authors found significant changes in microbial composition in stomach cancer patients compared to patients with pre-cancerous mucosal changes, with an increase of some and a depletion of other bacteria, in particular an increase in oral bacteria, which is also found in other gastrointestinal cancers. They also found that interactions between the depleted and enriched bacterial species progressively increased with progressing carcinogenesis. Whilst there was no difference in the diversity of bacteria between H. pylori-positive and negative samples, more bacterial interactions were observed in H. pylori-negative samples. The authors conclude that significant gastric dysbiosis can be seen in samples of stomach cancer patients, however, they point out that from their study it is impossible to tell whether the bacteria increased in GC are “drivers” or “passengers” of gastric carcinogenesis. Their call for more research focusses on using this knowledge to develop better diagnostic biomarkers, rather than using this information for prevention or treatment of stomach cancer.
Abstract
OBJECTIVES We aimed to characterise the microbial changes associated with histological stages of gastric tumourigenesis. DESIGN We performed 16S rRNA gene analysis of gastric mucosal samples from 81 cases including superficial gastritis (SG), atrophic gastritis (AG), intestinal metaplasia (IM) and gastric cancer (GC) from Xi'an, China, to determine mucosal microbiome dysbiosis across stages of GC. We validated the results in mucosal samples of 126 cases from Inner Mongolia, China. RESULTS We observed significant mucosa microbial dysbiosis in IM and GC subjects, with significant enrichment of 21 and depletion of 10 bacterial taxa in GC compared with SG (q<0.05). Microbial network analysis showed increasing correlation strengths among them with disease progression (p<0.001). Five GC-enriched bacterial taxa whose species identifications correspond to Peptostreptococcus stomatis, Streptococcus anginosus, Parvimonas micra, Slackia exigua and Dialister pneumosintes had significant centralities in the GC ecological network (p<0.05) and classified GC from SG with an area under the receiver-operating curve (AUC) of 0.82. Moreover, stronger interactions among gastric microbes were observed in Helicobacter pylori-negative samples compared with H. pylori-positive samples in SG and IM. The fold changes of selected bacteria, and strengths of their interactions were successfully validated in the Inner Mongolian cohort, in which the five bacterial markers distinguished GC from SG with an AUC of 0.81. CONCLUSIONS In addition to microbial compositional changes, we identified differences in bacterial interactions across stages of gastric carcinogenesis. The significant enrichments and network centralities suggest potentially important roles of P. stomatis, D. pneumosintes, S. exigua, P. micra and S. anginosus in GC progression.
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Dietary sulforaphane-rich broccoli sprouts reduce colonization and attenuate gastritis in Helicobacter pylori-infected mice and humans.
Yanaka, A, Fahey, JW, Fukumoto, A, Nakayama, M, Inoue, S, Zhang, S, Tauchi, M, Suzuki, H, Hyodo, I, Yamamoto, M
Cancer prevention research (Philadelphia, Pa.). 2009;2(4):353-60
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Helicobacter pylori infection is strongly associated with stomach cancer. Broccoli sprouts are rich in glucoraphanin, the precursor of sulforaphane and have been shown to be bactericidal against Helicobacter pylori infections. This study aimed to evaluate efficacy of broccoli sprouts in reducing H. pylori infection in high-salt, H. pylori–infected mice and infected humans. 6-wk-old mice were infected with H-Pylori and consumed a high salt diet for 2 months. High-salt diets exaggerate H. pylori–induced gastritis in mice. Mice were randomised into 2 groups receiving either broccoli sprouts in water or plain drinking water. Mice had free food access. 50 H. pylori–positive human volunteers whose endoscopy showed gastritis were randomised to consume 70 g/d of broccoli sprouts or equivalent of alfalfa sprouts for 8 weeks. Self reported compliance (95%) was confirmed by urine sample. In mice consuming the broccoli sprout water, inflammation was reduced, as were the cytokines unregulated by H. pylori infection. In humans, inflammation in the gastric lumen was significantly reduced in the broccoli sprout group only. Both stool and breath markers of H pylori were significantly lower when compared to control. The authors conclude that intake of sulforaphane-rich broccoli sprouts for 2 months reduces H. pylori colonization in mice and improves infection in H pylori positive mice and humans.
Abstract
The isothiocyanate sulforaphane [SF; 1-isothiocyanato-4(R)-methylsulfinylbutane] is abundant in broccoli sprouts in the form of its glucosinolate precursor (glucoraphanin). SF is powerfully bactericidal against Helicobacter pylori infections, which are strongly associated with the worldwide pandemic of gastric cancer. Oral treatment with SF-rich broccoli sprouts of C57BL/6 female mice infected with H. pylori Sydney strain 1 and maintained on a high-salt (7.5% NaCl) diet reduced gastric bacterial colonization, attenuated mucosal expression of tumor necrosis factor-alpha and interleukin-1beta, mitigated corpus inflammation, and prevented expression of high salt-induced gastric corpus atrophy. This therapeutic effect was not observed in mice in which the nrf2 gene was deleted, strongly implicating the important role of Nrf2-dependent antioxidant and anti-inflammatory proteins in SF-dependent protection. Forty-eight H. pylori-infected patients were randomly assigned to feeding of broccoli sprouts (70 g/d; containing 420 micromol of SF precursor) for 8 weeks or to consumption of an equal weight of alfalfa sprouts (not containing SF) as placebo. Intervention with broccoli sprouts, but not with placebo, decreased the levels of urease measured by the urea breath test and H. pylori stool antigen (both biomarkers of H. pylori colonization) and serum pepsinogens I and II (biomarkers of gastric inflammation). Values recovered to their original levels 2 months after treatment was discontinued. Daily intake of sulforaphane-rich broccoli sprouts for 2 months reduces H. pylori colonization in mice and improves the sequelae of infection in infected mice and in humans. This treatment seems to enhance chemoprotection of the gastric mucosa against H. pylori-induced oxidative stress.