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around abdominal organs raises the risk of heart disease, hypertension, and stroke","The microbes in our gut can influence how much energy we extract from food",1,{"id":36,"data":37,"type":38,"maxContentLevel":19,"version":34},"d3bfe66e-dbad-4b25-a1d2-14b0a870e3cf",{"type":38,"intro":39},10,[40,41],"How do gut microbes influence energy extraction from food?","What did Peter Turnbaugh's experiments with germ-free mice reveal about obesity?",[43,58,73],{"id":44,"data":45,"type":34,"maxContentLevel":19,"version":24,"reviews":48},"8ba3ad6f-9155-43b1-a0aa-b90931ead18e",{"type":34,"markdownContent":46,"audioMediaId":47},"We are living in an age of obesity. In *10% Human*, evolutionary biologist and science writer Alanna Collen notes that over half of the people in the Western world are either overweight or obese. When future generations learn about the twentieth century, she says, it will be remembered not only as the century in which two world wars were fought, or for the invention of the internet, but also as the age of obesity.\n\nOur collective struggle with obesity has disastrous consequences for our health. Being obese puts you at risk of developing type 2 diabetes and other endocrine disorders such as polycystic ovarian syndrome (PCOS), which affects female fertility. It even increases the risk of some cancers.","b6dbc27d-5292-48af-935b-adcb7e56abd5",[49],{"id":50,"data":51,"type":52,"version":34,"maxContentLevel":19},"804de11e-7084-4faa-b464-e67852a2db34",{"type":52,"reviewType":53,"spacingBehaviour":34,"clozeQuestion":54,"clozeWords":56},11,4,[55],"Alanna Collen argues that our era will be remembered as the era of obesity.",[57],"obesity",{"id":59,"data":60,"type":34,"maxContentLevel":19,"version":19,"reviews":63},"8936c399-a9a5-4c69-8d13-3dae361ff2bd",{"type":34,"markdownContent":61,"audioMediaId":62},"Visceral fat – fat accumulated and stored around the abdominal organs, typical of fat distribution in obese people – increases the risk of heart disease, hypertension, and stroke. But the struggle is not only personal: public health-care systems all over the world are groaning under the weight of the obesity epidemic.\n\n![Graph](image://8bdfed32-e1d5-4ac5-b607-ee21becc69bc \"Obesity rates around the world. Ly.n0m, CC BY 4.0 \u003Chttps://creativecommons.org/licenses/by/4.0>, via Wikimedia Commons\")\n\nIn response to the alarming rise in obesity levels worldwide, in the past few decades we have seen a societal obsession with restrictive diets and calorie counting. The age-old debate, according to Professor Tim Spector, author of *The Diet Myth*, has been whether low-fat or low-sugar diets yield better results.","c21d577d-eebb-4f44-bf09-900197461fd1",[64],{"id":65,"data":66,"type":52,"version":24,"maxContentLevel":19},"adb5bddc-cc00-444e-808b-a7372f8edec3",{"type":52,"reviewType":24,"spacingBehaviour":34,"binaryQuestion":67,"binaryCorrect":69,"binaryIncorrect":71},[68],"What is associated with visceral fat, commonly found in obese individuals?",[70],"Increased risk of heart disease, hypertension, and stroke",[72],"Decreased risk of type 2 diabetes and endocrine disorders",{"id":74,"data":75,"type":34,"maxContentLevel":19,"version":24,"reviews":78},"271d575a-4495-40b8-a104-33b288c5b461",{"type":34,"markdownContent":76,"audioMediaId":77},"But the rise in obesity has taken place against the backdrop of 60 years of scientific research into effective strategies for weight loss and weight maintenance. Some studies suggest that there may be more to the obesity struggle than calories in, calories out – and that it is not simply the calories we consume that make a difference to our weight, but the calories we absorb.\n\nWe can look, once again, to our microbiota for clues. In experiments with germ-free mice, former PhD student Peter Turnbaugh, now a professor at UCSF, discovered that it’s the particular set of microbes we harbor that determines our ability to extract energy from our food.","3e5feb01-598c-4e2a-8d9f-fc204c5ea90c",[79],{"id":80,"data":81,"type":52,"version":34,"maxContentLevel":19},"afa51e21-0d15-4d6f-b58e-83e3713dd032",{"type":52,"reviewType":24,"spacingBehaviour":34,"binaryQuestion":82,"binaryCorrect":84,"binaryIncorrect":86},[83],"What factor determines our ability to extract energy from food, according to Peter Turnbaugh's experiments with germ-free mice?",[85],"Our microbiota",[87],"Calorie counting",{"id":89,"data":90,"type":24,"version":24,"maxContentLevel":19,"summaryPage":92,"introPage":100,"pages":106},"a7e06193-e280-4bb4-8de6-96272c2c5444",{"type":24,"title":91},"The Role of the Microbiome in Metabolic Health",{"id":93,"data":94,"type":19,"maxContentLevel":19,"version":34},"d0518b3f-823e-4471-819e-f2ed89f5a9d4",{"type":19,"summary":95},[96,97,98,99],"Gut microbiota acts like an endocrine organ, maintaining body balance","Disruptions in gut microbiota can lead to chronic inflammation and insulin resistance","Higher LPS levels in the gut are linked to obesity and lower leptin production","Probiotics and prebiotic fibers can reduce LPS levels and improve metabolic health",{"id":101,"data":102,"type":38,"maxContentLevel":19,"version":34},"539a4ed3-77fd-43d2-8139-b8f09479ffa4",{"type":38,"intro":103},[104,105],"How does LPS influence insulin resistance?","What effect does LPS have on leptin production?",[107,133,168,185],{"id":108,"data":109,"type":34,"maxContentLevel":19,"version":24,"reviews":112},"5e9bd147-d07c-4822-a2db-1efefaf80f09",{"type":34,"markdownContent":110,"audioMediaId":111},"The gut microbiota is, in fact, considered a separate endocrine organ involved in maintaining systemic homeostasis within the host, much like the main endocrine organs – pituitary, thyroid, and adrenal glands. In this sense, our tiny hitchhikers are shapeshifters, able to emulate the functions of other organs.\n\nShifts in the composition of the gut microbiota caused by external factors (such as diet and antibiotics) can dramatically alter the symbiotic relationship between gut microbes and host. Common anti-bacterial household cleaning products like those containing triclosan can also disrupt the microbial composition of the gut. Triclosan has also been found to interfere with the action of thyroid hormones, and to block the action of estrogen and testosterone in human cells in petri dishes.","1fa56ab3-8d36-4d44-ad46-2fd9f8f52108",[113],{"id":114,"data":115,"type":52,"version":34,"maxContentLevel":19},"29079da0-6960-4cbb-b661-ad7bb4b231d1",{"type":52,"reviewType":19,"spacingBehaviour":34,"collapsingSiblings":116,"multiChoiceQuestion":120,"multiChoiceCorrect":122,"multiChoiceIncorrect":124,"multiChoiceMultiSelect":6,"multiChoiceRevealAnswerOption":6,"matchPairsQuestion":128,"matchPairsPairs":130},[117,118,119],"a69c9d0e-b186-4cf2-b3cd-a8958fb1f61e","df670885-0279-45f1-8f16-aadf765969f6","3cbbd6c9-1799-48dd-8ce3-a8e81d5d70fa",[121],"Which of the following best describes systemic homeostasis?",[123],"Balance within the body's systems",[125,126,127],"Overproduction of immune cells","Associated with the development of cancer cells","A classification of bacteria cell-wall types",[129],"Match the pairs below:",[131],{"left":132,"right":123,"direction":19},"Systemic homeostasis",{"id":134,"data":135,"type":34,"maxContentLevel":19,"version":24,"reviews":138},"e0142c71-1396-445d-bf5a-8092084f9de3",{"type":34,"markdownContent":136,"audioMediaId":137},"This disruption to immune homeostasis – referred to as dysbiosis – promotes the development of metabolic disease. In a state of dysbiosis, the immune system is activated by the production of cytokines, which leads to chronic, low-grade inflammation (this is called a ‘cytokine storm’). Mature immune cells are then recruited and activated in metabolic tissues – in particular, adipose tissues (body fat).\n\nThe result is that insulin signaling pathways are desensitized and the affected individual develops insulin resistance. The lipopolysaccharide (LPS) molecule is a major component of the outer membrane of certain bacteria, and its levels in the gut can influence metabolic health. Studies have shown that higher LPS levels are associated with increased inflammation and obesity.","25182305-0bdc-4371-9363-f4387f99835f",[139,148,159],{"id":140,"data":141,"type":52,"version":34,"maxContentLevel":19},"fa29c1b6-28a3-40ae-b15c-bdabc17e12cb",{"type":52,"reviewType":24,"spacingBehaviour":34,"binaryQuestion":142,"binaryCorrect":144,"binaryIncorrect":146},[143],"What is the term used to describe the disruption of immune homeostasis caused by shifts in gut microbiota composition?",[145],"Dysbiosis",[147],"Symbiosis",{"id":117,"data":149,"type":52,"version":34,"maxContentLevel":19},{"type":52,"reviewType":19,"spacingBehaviour":34,"collapsingSiblings":150,"multiChoiceQuestion":151,"multiChoiceCorrect":153,"multiChoiceIncorrect":154,"multiChoiceMultiSelect":6,"multiChoiceRevealAnswerOption":6,"matchPairsQuestion":155,"matchPairsPairs":156},[114,118,119],[152],"Which of the following best describes a cytokine storm?",[125],[123,126,127],[129],[157],{"left":158,"right":125,"direction":19},"Cytokine storm",{"id":160,"data":161,"type":52,"version":34,"maxContentLevel":19},"1f154427-c76a-4311-b6d7-23630962e326",{"type":52,"reviewType":24,"spacingBehaviour":34,"binaryQuestion":162,"binaryCorrect":164,"binaryIncorrect":166},[163],"What is the potential effect of lipopolysaccharide (LPS) on metabolic health and appetite regulation?",[165],"Increased inflammation and interference with leptin production",[167],"Decreased inflammation and enhanced insulin sensitivity",{"id":169,"data":170,"type":34,"maxContentLevel":19,"version":24,"reviews":173},"b07fcada-7e68-4238-b93f-184bde9c3c99",{"type":34,"markdownContent":171,"audioMediaId":172},"Additionally, research suggests that LPS may interfere with leptin production - a hormone which helps regulate appetite - leading to overeating and weight gain. Interestingly, some studies suggest that probiotics may help reduce LPS levels in the gut by competing for nutrients with pathogenic bacteria. This could potentially lead to improved metabolic health as well as reduced inflammation.\n\nFurthermore, prebiotic fibers such as those found in fruits and vegetables can also help promote healthy microbial populations which produce beneficial metabolites like short-chain fatty acids (SCFAs). SCFAs have been linked to improved insulin sensitivity and decreased risk of type 2 diabetes. The relationship between LPS levels and leptin production is complex, but it appears that higher levels of LPS can lead to decreased leptin production.","d30d72ab-87ed-4144-8ce8-a057c1b0709c",[174],{"id":175,"data":176,"type":52,"version":34,"maxContentLevel":19},"714367d6-d4a5-4d49-83ae-e59610f30ecf",{"type":52,"reviewType":19,"spacingBehaviour":34,"multiChoiceQuestion":177,"multiChoiceCorrect":179,"multiChoiceIncorrect":181,"multiChoiceMultiSelect":6,"multiChoiceRevealAnswerOption":6},[178],"Which molecules are associated with higher levels of obesity?",[180],"LPS",[182,183,184],"PDS","SIBO","FODMAP",{"id":186,"data":187,"type":34,"maxContentLevel":19,"version":24,"reviews":190},"c235130e-9147-4f19-8466-12345096cf00",{"type":34,"markdownContent":188,"audioMediaId":189},"This could explain why some people with obesity have lower than normal levels of the hormone. Additionally, research suggests that certain probiotics may help reduce LPS levels in the gut by competing for nutrients with pathogenic bacteria. For example, a study on mice found that supplementing their diet with Bifidobacterium longum reduced their body fat mass and improved glucose tolerance compared to those without supplementation. Interestingly, prebiotic fibers such as those found in fruits and vegetables can also help promote healthy microbial populations which produce beneficial metabolites like short-chain fatty acids (SCFAs).\n\nSCFAs are thought to play an important role in regulating energy metabolism by increasing insulin sensitivity and decreasing inflammation associated with metabolic disorders. In fact, one study showed that consuming a high-fiber diet was linked to lower concentrations of circulating LPS molecules - suggesting fiber intake may be beneficial for reducing inflammation related to metabolic diseases.","8cb7e6c2-d987-43d8-98d0-7437aa0323e6",[191],{"id":192,"data":193,"type":52,"version":34,"maxContentLevel":19},"0bae3f10-efef-470d-be5b-cefe8d24fea5",{"type":52,"reviewType":24,"spacingBehaviour":34,"binaryQuestion":194,"binaryCorrect":196,"binaryIncorrect":198},[195],"What is the potential benefit of consuming a high-fiber diet in relation to metabolic diseases?",[197],"Decreasing inflammation by lowering circulating LPS molecules",[199],"Increasing leptin production directly",{"id":201,"data":202,"type":24,"version":19,"maxContentLevel":19,"summaryPage":204,"introPage":212,"pages":218},"ae20a07a-561d-4388-9e95-abbecae53831",{"type":24,"title":203},"Microbes and Energy Storage",{"id":205,"data":206,"type":19,"maxContentLevel":19,"version":34},"6ddab3b0-b17b-4930-b1fd-b89609a2f1a2",{"type":19,"summary":207},[208,209,210,211],"LPS in the blood triggers inflammation and prevents new fat cells from forming","Obese people overfill existing fat cells instead of making new ones","Akkermansia bacteria boost mucus production, reducing LPS in the blood","Mice given Akkermansia lost weight and stored fat healthily",{"id":213,"data":214,"type":38,"maxContentLevel":19,"version":34},"41583f69-16da-46eb-87d0-af8f4aadea8e",{"type":38,"intro":215},[216,217],"How does LPS affect fat cells in obese people?","What role does Akkermansia play in weight regulation?",[219,234,249],{"id":220,"data":221,"type":34,"maxContentLevel":19,"version":24,"reviews":224},"3ec2cc7a-0eb5-4360-83f7-88d4882c2cca",{"type":34,"markdownContent":222,"audioMediaId":223},"When lipopolysaccharide (LPS) gets into the blood, it behaves like a toxin. Through his research Cani learned that obese people had high levels of LPS in their blood, and it was the LPS that was responsible for triggering inflammation in their fat cells. More importantly, he discovered that LPS was preventing new fat cells from forming – existing fat cells were simply being overfilled.\n\nThis tied in with the existing knowledge that when lean people store energy, they make new cells and fill them with small amounts of fat, whereas when obese people gain weight, they overfill existing fat cells, making the fat cells larger.","0b3a8bd4-2ce4-4d07-a7ce-cef634f2c909",[225],{"id":226,"data":227,"type":52,"version":34,"maxContentLevel":19},"381f1b44-dce5-4750-909b-612bcab43e0b",{"type":52,"reviewType":24,"spacingBehaviour":34,"binaryQuestion":228,"binaryCorrect":230,"binaryIncorrect":232},[229],"What is the role of lipopolysaccharide (LPS) in obesity according to Cani's research?",[231],"It triggers inflammation in fat cells and prevents new fat cells from forming",[233],"It helps in the formation of new fat cells and reduces inflammation in existing ones",{"id":235,"data":236,"type":34,"maxContentLevel":19,"version":24,"reviews":239},"76596f70-33d5-4fac-bad7-7ec2ebeb4ae5",{"type":34,"markdownContent":237,"audioMediaId":238},"This was an important discovery, because it showed that the fat of obese people was not just layers of stored energy, it was fat tissue that had biochemically malfunctioned, and LPS seemed to be causing that malfunction to occur.\n\nCani’s findings also challenged the traditional thinking about weight gain, by demonstrating that 'obesity is not always a lifestyle disease caused by overeating and being under-active. Rather, it is a dysfunction of the body’s energy-storage system.' If lipopolysaccharide (LPS) was causing the fat tissue of obese people to malfunction, the logical next step in the obesity puzzle was to figure out how to prevent LPS from seeping into the blood.","870de7d0-9fbc-4760-a0ab-c69fcbd88cec",[240],{"id":241,"data":242,"type":52,"version":34,"maxContentLevel":19},"f0a37502-4d97-4e51-885e-cb1fca46c1b7",{"type":52,"reviewType":24,"spacingBehaviour":34,"binaryQuestion":243,"binaryCorrect":245,"binaryIncorrect":247},[244],"Which of these would be a good way of preventing obesity, according to Cani?",[246],"Preventing LPS from entering the blood",[248],"Encouraging more LPS production in the gut",{"id":250,"data":251,"type":34,"maxContentLevel":19,"version":19,"reviews":254},"76b29536-b378-458c-bec4-792a45dae742",{"type":34,"markdownContent":252,"audioMediaId":253},"Akkermansia muciniphila is a bacterium that lives on the mucosal layer of the gut lining (‘muciniphila’ means mucus-loving). This mucus forms a protective barrier that prevents the microbiota from sneaking into the blood. In healthy individuals, Akkermansia accounts for about 4% of the intestinal bacteria. The more you have, the thicker your mucus layer, and the less LPS you’ll have in your blood. Akkermansia is responsible for persuading the cells in the gut lining to produce more mucus.\n\nCani tried supplementing the diets of a group of mice with Akkermansia. Their LPS levels dropped, they started to store fat in healthy ways, and – most importantly, they lost weight. Akkermansia also made the mice more sensitive to leptin, so their appetites decreased. Cani’s work showed that mice had gained weight not because they ate too much, but because the LPS was forcing their bodies to store energy instead of expending it.","0ada3c20-462b-4e8b-b9b6-71b57e9f07da",[255],{"id":256,"data":257,"type":52,"version":34,"maxContentLevel":19},"14feb7ee-9e5d-4e9d-bdab-177eed218095",{"type":52,"reviewType":19,"spacingBehaviour":34,"multiChoiceQuestion":258,"multiChoiceCorrect":260,"multiChoiceIncorrect":262,"multiChoiceMultiSelect":6,"multiChoiceRevealAnswerOption":6},[259],"Which bacteria is good for strengthening the mucus on the gut lining?",[261],"Akkermansia",[263,264,265],"Lactobacilli","H. Pylori","Bifidobacterium",{"id":267,"data":268,"type":24,"version":24,"maxContentLevel":19,"summaryPage":270,"introPage":278,"pages":284},"75e8a631-5c97-4f01-95d0-26671d519973",{"type":24,"title":269},"Antibiotics and Obesity",{"id":271,"data":272,"type":19,"maxContentLevel":19,"version":34},"6f782425-bcc4-4c14-9a64-b742b5f1eb72",{"type":19,"summary":273},[274,275,276,277],"Obesity rates spiked after antibiotics became widespread post-WWII","Antibiotics in farming likely ended up in our food, contributing to obesity","Early childhood antibiotic use can lead to obesity later in life","Gut bacteria influence weight more than genes, and can be changed",{"id":279,"data":280,"type":38,"maxContentLevel":19,"version":34},"d211e768-944a-4bfd-ba87-e41c14695482",{"type":38,"intro":281},[282,283],"How do antibiotics in early childhood affect obesity risk later in life?","What did Ruth Ley discover about the microbiota of obese vs. lean individuals?",[285,302,317],{"id":286,"data":287,"type":34,"maxContentLevel":19,"version":24,"reviews":290},"dc627166-aad4-4a17-97cb-a5afaff92b26",{"type":34,"markdownContent":288,"audioMediaId":289},"If you track the trajectory of the obesity epidemic, you’ll notice a rise in obesity levels worldwide starting in the 1950s, followed by a dramatic spike in the 1980s. In 10% Human, Collen surmises that this is no accident, as the timing of our expanding waistlines coincided with the mass roll-out of antibiotics after the end of the Second World War.\n\nLikewise, the spike in the 1980s occurred around the same time that we switched to intensive farming operations, which relied heavily on feeding antibiotics to livestock to promote growth. Collen speculates that the antibiotics used to fatten farm animals probably made their way onto our plates and into our tissues. Her view is backed up by Martin Blaser, whose studies showed a correlation between increased size (in terms of both weight and height) of humans and the accelerated use of antibiotics in farming, in the past few decades.","d52f258c-5ea3-4116-bc50-236cf19f8048",[291],{"id":292,"data":293,"type":52,"version":34,"maxContentLevel":19},"d0f2bebc-d61a-495c-9f8a-cdcb85b73175",{"type":52,"reviewType":19,"spacingBehaviour":34,"multiChoiceQuestion":294,"multiChoiceCorrect":296,"multiChoiceIncorrect":298,"multiChoiceMultiSelect":6,"multiChoiceRevealAnswerOption":6},[295],"What factor is believed to have contributed to the rise in obesity levels worldwide starting in the 1950s and spiking in the 1980s?",[297],"Mass roll-out of antibiotics and their use in intensive farming operations",[299,300,301],"Increased consumption of painkillers","The development of opioids such as Oxycontin","Mass roll-out of chemical pesticides",{"id":303,"data":304,"type":34,"maxContentLevel":19,"version":24,"reviews":307},"11b63e78-0942-42a5-92c1-540c7d637092",{"type":34,"markdownContent":305,"audioMediaId":306},"Blaser’s studies also showed that antibiotic use in young childhood predisposes you to obesity in later life. This is especially true before age 3, which is a critical period for early life development.\n\nIn 2004, Fredrik Bäckhed, a professor of microbiology at Gothenburg University in Sweden, cultivated germ-free mice in his lab. They were delivered by Caesarean-section, then kept in sterile chambers. Each mouse was a blank canvas – bred without microbiota, which meant that his team could colonize them with whichever microbes they wished to test their theories.\n\nBäckhed observed that the germ-free mice were leaner and had lower body fat than mice colonized with conventional microbiota. When colonized with the conventional gut microbiota, the germ-free mice gained weight and their body fat increased by 50%, despite the fact that they were eating less. This proved that the gut microbiota are essential for helping us extract energy from food and deposit fat in the body.","0e8106c9-1fca-4d56-bc10-b03d49fa1f7c",[308],{"id":309,"data":310,"type":52,"version":34,"maxContentLevel":19},"ad6bffab-da90-4399-ab56-f3df288ac331",{"type":52,"reviewType":24,"spacingBehaviour":34,"binaryQuestion":311,"binaryCorrect":313,"binaryIncorrect":315},[312],"What was the significant observation made by Fredrik Bäckhed in his germ-free mice experiment?",[314],"The germ-free mice were leaner and had lower body fat than mice with conventional microbiota",[316],"The germ-free mice had higher body fat and gained weight despite eating less",{"id":318,"data":319,"type":34,"maxContentLevel":19,"version":24,"reviews":322},"a32483bc-0bcb-469e-a1b0-8751effea0e1",{"type":34,"markdownContent":320,"audioMediaId":321},"Bäckhed’s research was furthered by microbiologist Ruth Ley in 2005. Using DNA sequencing, Ley compared the microbiotas of obese and lean mice. In both types of mice, two groups of bacteria were dominant: the Bacteroidetes and the Firmicutes. But the obese mice contained half as many Bacteroidetes as the lean mice. Ley then checked the microbiotas of lean and obese humans and found the same ratio – the obese people had far more Firmicutes and the lean people had a greater proportion of Bacteroidetes.\n\nPeter Turnbagh, a PhD student from the same lab, took the experiment one step further by transplanting the microbes of the obese mice into germ-free mice. At the same time, he transferred the microbes of lean mice into a second set of germ-free mice. Both sets of mice were fed exactly the same amount of food, but fourteen days later, the mice colonized with the ‘obese’ microbiota had gotten fat, and those with the ‘lean’ microbiota had not.\n\nThese findings were promising because they showed that our microbiota have a bigger influence on our metabolism than our genes – and our microbiota can be altered.","2f3b6982-b781-4118-96d8-ff6fb6803669",[323],{"id":324,"data":325,"type":52,"version":34,"maxContentLevel":19},"5b222b0f-15f8-4e7f-88ea-0e27668bc249",{"type":52,"reviewType":19,"spacingBehaviour":34,"multiChoiceQuestion":326,"multiChoiceCorrect":328,"multiChoiceIncorrect":330,"multiChoiceMultiSelect":6,"multiChoiceRevealAnswerOption":6},[327],"What was the difference in the proportion of Bacteroidetes and Firmicutes between obese and lean mice in Ruth Ley's research?",[329],"Obese mice had half as many Bacteroidetes as lean mice.",[331,332,333],"Obese mice had twice as many Bacteroidetes as lean mice","Obese mice had equal amounts of Bacteroidetes and Firmicutes","Lean mice had three times as many Bacteroidetes as obese mice",[335,419,489,542],{"id":22,"data":23,"type":24,"version":19,"maxContentLevel":19,"summaryPage":26,"introPage":35,"pages":336},[337,368,402],{"id":44,"data":45,"type":34,"maxContentLevel":19,"version":24,"reviews":48,"parsed":338},{"data":339,"body":342,"toc":366},{"title":340,"description":341},"","We are living in an age of obesity. In 10% Human, evolutionary biologist and science writer Alanna Collen notes that over half of the people in the Western world are either overweight or obese. When future generations learn about the twentieth century, she says, it will be remembered not only as the century in which two world wars were fought, or for the invention of the internet, but also as the age of obesity.",{"type":343,"children":344},"root",[345,361],{"type":346,"tag":347,"props":348,"children":349},"element","p",{},[350,353,359],{"type":351,"value":352},"text","We are living in an age of obesity. In ",{"type":346,"tag":354,"props":355,"children":356},"em",{},[357],{"type":351,"value":358},"10% Human",{"type":351,"value":360},", evolutionary biologist and science writer Alanna Collen notes that over half of the people in the Western world are either overweight or obese. When future generations learn about the twentieth century, she says, it will be remembered not only as the century in which two world wars were fought, or for the invention of the internet, but also as the age of obesity.",{"type":346,"tag":347,"props":362,"children":363},{},[364],{"type":351,"value":365},"Our collective struggle with obesity has disastrous consequences for our health. Being obese puts you at risk of developing type 2 diabetes and other endocrine disorders such as polycystic ovarian syndrome (PCOS), which affects female fertility. It even increases the risk of some cancers.",{"title":340,"searchDepth":24,"depth":24,"links":367},[],{"id":59,"data":60,"type":34,"maxContentLevel":19,"version":19,"reviews":63,"parsed":369},{"data":370,"body":372,"toc":400},{"title":340,"description":371},"Visceral fat – fat accumulated and stored around the abdominal organs, typical of fat distribution in obese people – increases the risk of heart disease, hypertension, and stroke. But the struggle is not only personal: public health-care systems all over the world are groaning under the weight of the obesity epidemic.",{"type":343,"children":373},[374,378,388],{"type":346,"tag":347,"props":375,"children":376},{},[377],{"type":351,"value":371},{"type":346,"tag":347,"props":379,"children":380},{},[381],{"type":346,"tag":382,"props":383,"children":387},"img",{"alt":384,"src":385,"title":386},"Graph","image://8bdfed32-e1d5-4ac5-b607-ee21becc69bc","Obesity rates around the world. Ly.n0m, CC BY 4.0 \u003Chttps://creativecommons.org/licenses/by/4.0>, via Wikimedia Commons",[],{"type":346,"tag":347,"props":389,"children":390},{},[391,393,398],{"type":351,"value":392},"In response to the alarming rise in obesity levels worldwide, in the past few decades we have seen a societal obsession with restrictive diets and calorie counting. The age-old debate, according to Professor Tim Spector, author of ",{"type":346,"tag":354,"props":394,"children":395},{},[396],{"type":351,"value":397},"The Diet Myth",{"type":351,"value":399},", has been whether low-fat or low-sugar diets yield better results.",{"title":340,"searchDepth":24,"depth":24,"links":401},[],{"id":74,"data":75,"type":34,"maxContentLevel":19,"version":24,"reviews":78,"parsed":403},{"data":404,"body":406,"toc":417},{"title":340,"description":405},"But the rise in obesity has taken place against the backdrop of 60 years of scientific research into effective strategies for weight loss and weight maintenance. Some studies suggest that there may be more to the obesity struggle than calories in, calories out – and that it is not simply the calories we consume that make a difference to our weight, but the calories we absorb.",{"type":343,"children":407},[408,412],{"type":346,"tag":347,"props":409,"children":410},{},[411],{"type":351,"value":405},{"type":346,"tag":347,"props":413,"children":414},{},[415],{"type":351,"value":416},"We can look, once again, to our microbiota for clues. In experiments with germ-free mice, former PhD student Peter Turnbaugh, now a professor at UCSF, discovered that it’s the particular set of microbes we harbor that determines our ability to extract energy from our food.",{"title":340,"searchDepth":24,"depth":24,"links":418},[],{"id":89,"data":90,"type":24,"version":24,"maxContentLevel":19,"summaryPage":92,"introPage":100,"pages":420},[421,438,455,472],{"id":108,"data":109,"type":34,"maxContentLevel":19,"version":24,"reviews":112,"parsed":422},{"data":423,"body":425,"toc":436},{"title":340,"description":424},"The gut microbiota is, in fact, considered a separate endocrine organ involved in maintaining systemic homeostasis within the host, much like the main endocrine organs – pituitary, thyroid, and adrenal glands. In this sense, our tiny hitchhikers are shapeshifters, able to emulate the functions of other organs.",{"type":343,"children":426},[427,431],{"type":346,"tag":347,"props":428,"children":429},{},[430],{"type":351,"value":424},{"type":346,"tag":347,"props":432,"children":433},{},[434],{"type":351,"value":435},"Shifts in the composition of the gut microbiota caused by external factors (such as diet and antibiotics) can dramatically alter the symbiotic relationship between gut microbes and host. Common anti-bacterial household cleaning products like those containing triclosan can also disrupt the microbial composition of the gut. Triclosan has also been found to interfere with the action of thyroid hormones, and to block the action of estrogen and testosterone in human cells in petri dishes.",{"title":340,"searchDepth":24,"depth":24,"links":437},[],{"id":134,"data":135,"type":34,"maxContentLevel":19,"version":24,"reviews":138,"parsed":439},{"data":440,"body":442,"toc":453},{"title":340,"description":441},"This disruption to immune homeostasis – referred to as dysbiosis – promotes the development of metabolic disease. In a state of dysbiosis, the immune system is activated by the production of cytokines, which leads to chronic, low-grade inflammation (this is called a ‘cytokine storm’). Mature immune cells are then recruited and activated in metabolic tissues – in particular, adipose tissues (body fat).",{"type":343,"children":443},[444,448],{"type":346,"tag":347,"props":445,"children":446},{},[447],{"type":351,"value":441},{"type":346,"tag":347,"props":449,"children":450},{},[451],{"type":351,"value":452},"The result is that insulin signaling pathways are desensitized and the affected individual develops insulin resistance. The lipopolysaccharide (LPS) molecule is a major component of the outer membrane of certain bacteria, and its levels in the gut can influence metabolic health. Studies have shown that higher LPS levels are associated with increased inflammation and obesity.",{"title":340,"searchDepth":24,"depth":24,"links":454},[],{"id":169,"data":170,"type":34,"maxContentLevel":19,"version":24,"reviews":173,"parsed":456},{"data":457,"body":459,"toc":470},{"title":340,"description":458},"Additionally, research suggests that LPS may interfere with leptin production - a hormone which helps regulate appetite - leading to overeating and weight gain. Interestingly, some studies suggest that probiotics may help reduce LPS levels in the gut by competing for nutrients with pathogenic bacteria. This could potentially lead to improved metabolic health as well as reduced inflammation.",{"type":343,"children":460},[461,465],{"type":346,"tag":347,"props":462,"children":463},{},[464],{"type":351,"value":458},{"type":346,"tag":347,"props":466,"children":467},{},[468],{"type":351,"value":469},"Furthermore, prebiotic fibers such as those found in fruits and vegetables can also help promote healthy microbial populations which produce beneficial metabolites like short-chain fatty acids (SCFAs). SCFAs have been linked to improved insulin sensitivity and decreased risk of type 2 diabetes. The relationship between LPS levels and leptin production is complex, but it appears that higher levels of LPS can lead to decreased leptin production.",{"title":340,"searchDepth":24,"depth":24,"links":471},[],{"id":186,"data":187,"type":34,"maxContentLevel":19,"version":24,"reviews":190,"parsed":473},{"data":474,"body":476,"toc":487},{"title":340,"description":475},"This could explain why some people with obesity have lower than normal levels of the hormone. Additionally, research suggests that certain probiotics may help reduce LPS levels in the gut by competing for nutrients with pathogenic bacteria. For example, a study on mice found that supplementing their diet with Bifidobacterium longum reduced their body fat mass and improved glucose tolerance compared to those without supplementation. Interestingly, prebiotic fibers such as those found in fruits and vegetables can also help promote healthy microbial populations which produce beneficial metabolites like short-chain fatty acids (SCFAs).",{"type":343,"children":477},[478,482],{"type":346,"tag":347,"props":479,"children":480},{},[481],{"type":351,"value":475},{"type":346,"tag":347,"props":483,"children":484},{},[485],{"type":351,"value":486},"SCFAs are thought to play an important role in regulating energy metabolism by increasing insulin sensitivity and decreasing inflammation associated with metabolic disorders. In fact, one study showed that consuming a high-fiber diet was linked to lower concentrations of circulating LPS molecules - suggesting fiber intake may be beneficial for reducing inflammation related to metabolic diseases.",{"title":340,"searchDepth":24,"depth":24,"links":488},[],{"id":201,"data":202,"type":24,"version":19,"maxContentLevel":19,"summaryPage":204,"introPage":212,"pages":490},[491,508,525],{"id":220,"data":221,"type":34,"maxContentLevel":19,"version":24,"reviews":224,"parsed":492},{"data":493,"body":495,"toc":506},{"title":340,"description":494},"When lipopolysaccharide (LPS) gets into the blood, it behaves like a toxin. Through his research Cani learned that obese people had high levels of LPS in their blood, and it was the LPS that was responsible for triggering inflammation in their fat cells. More importantly, he discovered that LPS was preventing new fat cells from forming – existing fat cells were simply being overfilled.",{"type":343,"children":496},[497,501],{"type":346,"tag":347,"props":498,"children":499},{},[500],{"type":351,"value":494},{"type":346,"tag":347,"props":502,"children":503},{},[504],{"type":351,"value":505},"This tied in with the existing knowledge that when lean people store energy, they make new cells and fill them with small amounts of fat, whereas when obese people gain weight, they overfill existing fat cells, making the fat cells larger.",{"title":340,"searchDepth":24,"depth":24,"links":507},[],{"id":235,"data":236,"type":34,"maxContentLevel":19,"version":24,"reviews":239,"parsed":509},{"data":510,"body":512,"toc":523},{"title":340,"description":511},"This was an important discovery, because it showed that the fat of obese people was not just layers of stored energy, it was fat tissue that had biochemically malfunctioned, and LPS seemed to be causing that malfunction to occur.",{"type":343,"children":513},[514,518],{"type":346,"tag":347,"props":515,"children":516},{},[517],{"type":351,"value":511},{"type":346,"tag":347,"props":519,"children":520},{},[521],{"type":351,"value":522},"Cani’s findings also challenged the traditional thinking about weight gain, by demonstrating that 'obesity is not always a lifestyle disease caused by overeating and being under-active. Rather, it is a dysfunction of the body’s energy-storage system.' If lipopolysaccharide (LPS) was causing the fat tissue of obese people to malfunction, the logical next step in the obesity puzzle was to figure out how to prevent LPS from seeping into the blood.",{"title":340,"searchDepth":24,"depth":24,"links":524},[],{"id":250,"data":251,"type":34,"maxContentLevel":19,"version":19,"reviews":254,"parsed":526},{"data":527,"body":529,"toc":540},{"title":340,"description":528},"Akkermansia muciniphila is a bacterium that lives on the mucosal layer of the gut lining (‘muciniphila’ means mucus-loving). This mucus forms a protective barrier that prevents the microbiota from sneaking into the blood. In healthy individuals, Akkermansia accounts for about 4% of the intestinal bacteria. The more you have, the thicker your mucus layer, and the less LPS you’ll have in your blood. Akkermansia is responsible for persuading the cells in the gut lining to produce more mucus.",{"type":343,"children":530},[531,535],{"type":346,"tag":347,"props":532,"children":533},{},[534],{"type":351,"value":528},{"type":346,"tag":347,"props":536,"children":537},{},[538],{"type":351,"value":539},"Cani tried supplementing the diets of a group of mice with Akkermansia. Their LPS levels dropped, they started to store fat in healthy ways, and – most importantly, they lost weight. Akkermansia also made the mice more sensitive to leptin, so their appetites decreased. Cani’s work showed that mice had gained weight not because they ate too much, but because the LPS was forcing their bodies to store energy instead of expending it.",{"title":340,"searchDepth":24,"depth":24,"links":541},[],{"id":267,"data":268,"type":24,"version":24,"maxContentLevel":19,"summaryPage":270,"introPage":278,"pages":543},[544,561,583],{"id":286,"data":287,"type":34,"maxContentLevel":19,"version":24,"reviews":290,"parsed":545},{"data":546,"body":548,"toc":559},{"title":340,"description":547},"If you track the trajectory of the obesity epidemic, you’ll notice a rise in obesity levels worldwide starting in the 1950s, followed by a dramatic spike in the 1980s. In 10% Human, Collen surmises that this is no accident, as the timing of our expanding waistlines coincided with the mass roll-out of antibiotics after the end of the Second World War.",{"type":343,"children":549},[550,554],{"type":346,"tag":347,"props":551,"children":552},{},[553],{"type":351,"value":547},{"type":346,"tag":347,"props":555,"children":556},{},[557],{"type":351,"value":558},"Likewise, the spike in the 1980s occurred around the same time that we switched to intensive farming operations, which relied heavily on feeding antibiotics to livestock to promote growth. Collen speculates that the antibiotics used to fatten farm animals probably made their way onto our plates and into our tissues. Her view is backed up by Martin Blaser, whose studies showed a correlation between increased size (in terms of both weight and height) of humans and the accelerated use of antibiotics in farming, in the past few decades.",{"title":340,"searchDepth":24,"depth":24,"links":560},[],{"id":303,"data":304,"type":34,"maxContentLevel":19,"version":24,"reviews":307,"parsed":562},{"data":563,"body":565,"toc":581},{"title":340,"description":564},"Blaser’s studies also showed that antibiotic use in young childhood predisposes you to obesity in later life. This is especially true before age 3, which is a critical period for early life development.",{"type":343,"children":566},[567,571,576],{"type":346,"tag":347,"props":568,"children":569},{},[570],{"type":351,"value":564},{"type":346,"tag":347,"props":572,"children":573},{},[574],{"type":351,"value":575},"In 2004, Fredrik Bäckhed, a professor of microbiology at Gothenburg University in Sweden, cultivated germ-free mice in his lab. They were delivered by Caesarean-section, then kept in sterile chambers. Each mouse was a blank canvas – bred without microbiota, which meant that his team could colonize them with whichever microbes they wished to test their theories.",{"type":346,"tag":347,"props":577,"children":578},{},[579],{"type":351,"value":580},"Bäckhed observed that the germ-free mice were leaner and had lower body fat than mice colonized with conventional microbiota. When colonized with the conventional gut microbiota, the germ-free mice gained weight and their body fat increased by 50%, despite the fact that they were eating less. This proved that the gut microbiota are essential for helping us extract energy from food and deposit fat in the body.",{"title":340,"searchDepth":24,"depth":24,"links":582},[],{"id":318,"data":319,"type":34,"maxContentLevel":19,"version":24,"reviews":322,"parsed":584},{"data":585,"body":587,"toc":603},{"title":340,"description":586},"Bäckhed’s research was furthered by microbiologist Ruth Ley in 2005. Using DNA sequencing, Ley compared the microbiotas of obese and lean mice. In both types of mice, two groups of bacteria were dominant: the Bacteroidetes and the Firmicutes. But the obese mice contained half as many Bacteroidetes as the lean mice. Ley then checked the microbiotas of lean and obese humans and found the same ratio – the obese people had far more Firmicutes and the lean people had a greater proportion of Bacteroidetes.",{"type":343,"children":588},[589,593,598],{"type":346,"tag":347,"props":590,"children":591},{},[592],{"type":351,"value":586},{"type":346,"tag":347,"props":594,"children":595},{},[596],{"type":351,"value":597},"Peter Turnbagh, a PhD student from the same lab, took the experiment one step further by transplanting the microbes of the obese mice into germ-free mice. At the same time, he transferred the microbes of lean mice into a second set of germ-free mice. Both sets of mice were fed exactly the same amount of food, but fourteen days later, the mice colonized with the ‘obese’ microbiota had gotten fat, and those with the ‘lean’ microbiota had not.",{"type":346,"tag":347,"props":599,"children":600},{},[601],{"type":351,"value":602},"These findings were promising because they showed that our microbiota have a bigger influence on our metabolism than our genes – and our microbiota can be altered.",{"title":340,"searchDepth":24,"depth":24,"links":604},[],{"left":4,"top":4,"width":606,"height":606,"rotate":4,"vFlip":6,"hFlip":6,"body":607},24,"\u003Cpath fill=\"none\" stroke=\"currentColor\" stroke-linecap=\"round\" stroke-linejoin=\"round\" stroke-width=\"2\" d=\"m9 18l6-6l-6-6\"/>",{"left":4,"top":4,"width":606,"height":606,"rotate":4,"vFlip":6,"hFlip":6,"body":609},"\u003Cpath fill=\"none\" stroke=\"currentColor\" stroke-linecap=\"round\" stroke-linejoin=\"round\" stroke-width=\"2\" d=\"M4 5h16M4 12h16M4 19h16\"/>",1778179387565]