RESEARCH

1. How the Microbiome Could Be the Key to New Cancer Treatments

Chemical engineer Stephanie Culler was just 13 years old when both her grandmothers died of cancer within six months of each other. Confronting the cruel randomness of the disease is tough for any young teenager, but Culler was further confused by an American Cancer Society poster on her parents’ refrigerator. “These good food choices may help protect you against certain cancers,” read the poster text accompanying 30 beautifully photographed fruits and vegetables. But Culler’s grandmothers, one who had lung cancer and the other colon cancer, already ate most of those foods. In fact, her maternal grandmother, an immigrant from Iran, stuck to the traditional Persian cuisine of chopped salads, grilled veggies and pomegranates that would rival any American diet in sheer anti-oxidant glory. Her diet also included gut-friendly fermented foods like homemade yogurt and pickled vegetables. As far as Culler could tell at the time, her grandmothers should have been spared. Culler and other oncology researchers hope to answer one of the most pressing questions in current cancer research: Does the quality and diversity of human gut bacteria determine whether people will successfully respond to cancer treatment? “When we looked at stool from breast and lung cancer patients, we discovered that important bacteria were missing from the microbiome,” Culler says. Over the last decade, there’s been a flurry of research exploring the microbiome’s role in everything from depression to autism to Parkinson’s disease. Studying the microbiome can help determine which patients are likely to respond to different pain and heart drugs, according to Rob Knight, founding director of the Center for Microbiome Innovation at the University of California San Diego. “We’re extremely interested in the interplay between food, drugs and the gut microbiome,” says Knight, who also cofounded the American Gut Project, a citizen science effort that has collected fecal samples from more than 11,300 participants in 42 countries. While the connection between gut bacteria and health is becoming clearer, scientists have struggled to successfully manipulate the microbiome as a form of treatment. “We know more than ever about how the microbiome influences chronic disease,” Knight says, “but what we don’t know yet is how to change your microbiome in a particular direction.” (Researchers do agree, however, that probiotics aren’t the godsend some people think they are.) In the meantime, Culler joins a chorus of researchers trying to bring attention to the biggest barrier to their research: lack of stool samples. Scientists need donations from cancer patients, cancer survivors, people with a family history of cancer and everyone else. “I’m always surprised why it’s so difficult to get samples,” Culler says. “People think it’s gross and are embarrassed. But I’m grateful for the cultural acceptance of the poop emoji for destigmatizing it.” Culler even launched “Poop for the Cure”, a research project that offers $50 Visa gift cards for samples. “Hopefully there will be a day when collecting stool will be as routine as collecting blood. Until then, we need everyone to help out.”

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2. Clues about autism may come from the gut

Bacterial flora inhabiting the human gut have become one of the hottest topics in biological research. Implicated in a range of important activities including digestion, fine-tuning body weight, regulating immune response, and producing neurotransmitters affect that brain and behavior, these tiny workers form diverse communities. Hundreds of species inhabit the gut, and although most are beneficial, some can be very dangerous. In new research appearing in the journal PLOS ONE, a team led by Rosa Krajmalnik-Brown, a researcher at Arizona State University's Biodesign Institute, present the first comprehensive bacterial analysis focusing on commensal or beneficial bacteria in children with autism spectrum disorder (ASD). After publishing earlier research exploring crucial links between intestinal microflora and gastric bypass, Krajmlanik-Brown convinced James Adams— director of the ASU Autism/Asperger's Research Program—that similar high throughput techniques could be used to mine the microbiome of patients with autism. (Previously, Adams had been studying the relationship between the gut microbiome and autism using traditional culturing techniques.) Following up on these tantalizing hints, the group hypothesized the existence of distinctive features in the intestinal microflora found in autistic subjects compared to typical children. The current study confirmed these suspicions, and found that children with autism had significantly fewer types of gut bacteria, probably making them more vulnerable to pathogenic bacteria. Autistic subjects also had significantly lower amounts of three critical bacteria, Prevotella, Coprococcus, and Veillonellaceae. Krajmalnik-Brown and lead author Dae-Wook Kang are researchers in the Biodesign Institute's Swette Center for Environmental Biotechnology, which is devoted to the use of microbial communities for the benefit of human and environmental health. Their new study is the first to approach autism from a different angle, by examining the possible role of so-called commensal or beneficial bacteria. Up to a quadrillion (1014) bacteria inhabit the human intestine, contributing to digestion, producing vitamins and promoting GI health. Genes associated with human intestinal flora are 100 times as plentiful as the body's human genes, forming what some have referred to as a second genome. Various environmental factors can destabilize the natural microbiome of the gut, including antibiotics and specific diets. Lower diversity of gut microbes was positively correlated with the presence of autistic symptoms in the study. The authors stress that bacterial richness and diversity are essential for maintaining a robust and adaptable bacterial community capable of fighting off environmental challenges. "We believe that a diverse gut is a healthy gut," Krajmalnik-Brown says. Among the fully classified genera in the study, Prevotella was the most conspicuously reduced in autistic subjects. Prevotella is believed to play a key role in the composition of the human gut microbiome. For this reason, the group undertook a sub-genus investigation of autistic subjects. They found that a species known as Prevotella copri occurred only in very low levels in the autistic samples. The species is a common component in normal children exhibiting more diverse and robust microbial communities.

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3. Influence of Probiotic Supplementation on Brain Function: Involvement of Gut Microbiome, Inflammation, and Stress Pathway

Probiotics were reported for several physical and psychological health benefits. Probiotics can positively alter the gut microbiome and nourish the commensal microbial load. Recent studies revealed that the cognitive functions (anxiety and depression) of human beings are meticulously associated with their genetic makeup, food habits, and gut microbiome. The gut microbiome may communicate with the brain through neural and humoral pathways, while involving several neurotransmitters and signaling molecules. The immune response, especially inflammatory system, plays a critical role in the microbiome and in mental health. Thus, many studies were conducted to explore the beneficial effect of probiotic, single and multistrain, formulations. Fruitful results were observed, but the underlying mechanism of probiotic-mediated improvement of mental health is not fully illustrated, even though some studies explained that the production of neurotransmitter-like metabolites by the probiotic strain could be the possible mediator of gut-brain axis. The present chapter summarizes the outcome of probiotic-based treatment for the improvement of stress and depression with respect to microbiome change, inflammation, and stress pathway.

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