The findings, published in Cell Reports, point to new avenues for preventing and treating the condition.

Although genetics play a role, obesity is mainly driven by lifestyle changes, including reduced physical activity and diets rich in highly processed foods. The gut microbiota is known to influence obesity, and emerging evidence suggests that people with obesity have less diverse and more inflammatory oral bacteria. But it is unclear whether and how oral bacteria may affect whole-body metabolism.

So, Ahmed Shibl at New York University Abu Dhabi in the United Arab Emirates and his colleagues analyzed data from the UAE Healthy Future Study, a project designed to understand factors that contribute to heart and metabolic diseases among Emirati adults.

Microbiota differences

The researchers analyzed data from 669 participants aged 18 to 43, collecting mouthwash samples, health measurements such as body weight, blood pressure, and cholesterol, and detailed lifestyle information, including smoking and exercise habits. 

By analyzing mouth bacteria, the team found that obesity was associated with distinct bacterial communities, lower microbial diversity, and increased levels of microbes linked to inflammation.

The researchers also found that many microbial pathways involved in breaking down sugars and generating obesity-related compounds were more active in obese people than in healthy-weight people.

Therapeutic strategies 

Compared to healthy-weight individuals, those with obesity had higher levels of molecules that are known to promote inflammation, interfere with insulin signaling, increase hunger, and raise the risk of diabetes and fatty liver disease. At the same time, people with obesity showed reduced microbial pathways responsible for making essential B vitamins, which are important for healthy energy use.

Computer models combining oral bacteria, their metabolic functions, and saliva chemicals could better distinguish obese from healthy individuals compared with clinical measurements alone. 

These results indicate a potential role of mouth bacteria in obesity-related diseases, the authors say. The findings, they add, “also suggest opportunities for microbiome-based prevention and therapeutic strategies against obesity and underscore the importance of investigating the oral microbiome’s contributions to other complex diseases.”

The findings, published in Nature Communications, suggest that gut microbiota profiles can help support personalized dietary interventions.

Lifestyle changes such as diet and exercise can help people with prediabetes, but individual responses vary due to differences in genetics and gut bacteria. The gut microbiota plays a key role in breaking down dietary fiber to improve insulin activity. However, whether microbial features can predict individual response remains unclear. 

Researchers led by Delei Song at Shanghai Jiao Tong University in China enrolled more than 800 people with prediabetes in a clinical study to investigate whether, and how, dietary fiber supplements can help improve blood sugar control.

Prediabetes subgroups

Study participants were randomly assigned to receive standard care with or without fiber supplements. Researchers grouped participants using multiple health measures, including age, weight, and blood sugar, rather than just blood sugar, and analyzed their gut microbiota. 

This approach identified four subgroups of people with prediabetes, each with distinct health profiles, such as differences in insulin production, heart and liver health, and family history of diabetes. These subgroups also showed differences in gut bacteria and blood metabolites, with some having less diverse gut microbiotas.

Only two of these subgroups benefited from dietary fiber, and this improvement depended on whether their gut bacteria could respond to fiber, the researchers found. 

Personalized medicine 

To predict who would benefit from dietary fiber, they researchers created a score based on changes in three key blood sugar measures. Then, they used machine learning to link these outcomes to specific gut bacteria. A set of specific gut bacteria could predict with good accuracy whether a person would respond well to fiber, the team found. 

Next, the researchers tested this approach in two independent groups of people with type 2 diabetes, showing it could predict both short-term and long-term benefits.

“Our study suggests that the gut microbiota response influences the effectiveness of dietary fiber intervention and provides a clinically applicable model to guide microbiome-targeted personalized medicine for prediabetes,” the authors say.

The findings, published in Cell Metabolism, may explain why some people respond better to exercise than others.

Previous studies suggested that gut microbes and certain amino acids might interfere with the benefits of exercise, but the exact mechanisms aren’t clear. So, researchers led by Yao Wang analyzed how overweight and obese men with prediabetes responded to a 12-week high-intensity exercise program in terms of insulin sensitivity and blood sugar control. 

The team also looked at obese mice to understand how gut microbes, the amino acid leucine, and fat cells influence exercise benefits.

Immune molecules

After 12 weeks of exercise, many circulating immune molecules changed similarly in all participants, but one molecule called sIL-6R decreased in people who responded well to exercise and increased in non-responders. Higher sIL-6R levels were linked to insulin resistance and inflammation. 

Further analyses showed that white fat tissue is the main source of sIL-6R, especially in obese men. This means that fat tissue not only stores energy but also influences how the body responds to exercise, the authors say.

In obese mice, exercise lowered the levels of sIL-6R, and artificially increasing sIL-6R blocked the benefits of exercise on insulin and blood sugar. The amino acid leucine also triggered fat cells to release sIL-6R, but blocking its production in fat cells could reverse this effect. 

Diabetes prevention

Mice receiving microbes from people who respond poorly to exercise showed higher blood levels of leucine and sIL-6R as well as worse insulin sensitivity, reduced blood sugar control, and more inflammation in fat tissue. Instead, mice receiving microbes from responders had lower levels of sIL-6R and improved metabolism. 

Further experiments showed that blocking sIL-6R or its production in fat cells reversed the negative effects observed in mice receiving microbes from people who respond poorly to exercise. Reducing sIL-6R also restored insulin sensitivity and lowered inflammation. 

Although factors such as sex and variability in gut microbiota colonization may affect the generalizability of the findings, the authors say, “therapeutic interventions targeting adipocyte-derived sIL-6R represent a promising strategy for maximizing exercise efficacy in personalized diabetes prevention.”

The findings, published in Cell Reports Medicine, suggest that glucocorticoids can alter metabolic and immune regulation by reshaping gut microbial functions.

Glucocorticoid hormones, a type of steroid hormones, help regulate metabolism, immunity, stress, and other processes, but too much can cause insulin resistance, increased infection risk, bone loss, and metabolic disruptions. Previous research suggests that glucocorticoids may alter the gut microbiota, which influences metabolism and immune health, but it remains unclear whether these changes come from direct effects on gut bacteria.

So, researchers led by Liwei Lyu at Herlev-Gentofte University Hospital in Denmark set up a clinical trial to study how glucocorticoids affected the gut microbiota, metabolism, and immunity in healthy young men.

Glucocorticoid treatment 

For seven days, study participants received either oral or injected glucocorticoids or no treatment. Glucocorticoid treatment was well tolerated with no major side effects reported. While overall blood sugar levels didn’t change, people who received oral glucocorticoids had lower inflammation markers and higher insulin levels.

Oral glucocorticoid treatment also resulted in signs of reduced insulin sensitivity, meaning the body had to produce more insulin to manage the same amount of sugar. 

These changes were linked to increased levels of bacteria such as Turicibacter bilis, Blautia, and Collinsella as well as lower levels of Sutterella wadsworthensis, Dysosmobacter welbionis, and several Clostridium and Lachnospira species. People who received injected glucocorticoids showed fewer changes, the researchers found. 

Altering metabolism

In people who received oral glucocorticoids, microbial pathways involved in breaking down sugars and fats were more active, suggesting that these bacteria may process glucose and lipids differently. Some amino acid and vitamin-related pathways were also affected. 

Using computer models, the researchers predicted that oral glucocorticoids increase the levels of certain microbial metabolites that reduce inflammation. Injected glucocorticoids had smaller effects and mostly influenced sugar-processing pathways. 

The findings indicate that glucocorticoids can alter gut microbial metabolism in ways that may influence the body’s metabolic and immune functions, the authors say. “Overall, the outcome of the present clinically controlled trial highlights the nuanced relationship between glucocorticoid therapy, gut microbiota, and host metabolic and systemic immune responses.”

The findings, published in Cell Metabolism, suggest that this approach is a promising way to help manage obesity by targeting gut bacteria and metabolism together.

Scientists have been long exploring ways to improve metabolism by targeting gut bacteria. For example, prebiotics such as fiber help good bacteria to grow, but they work differently for everyone. Previous research showed that delivering acetate to the lower gut using a special fiber, called acetylated cellulose (AceCel), may boost metabolism by influencing both the microbiota and the host’s metabolism. 

Building on those findings, researchers led by Tadashi Takeuchi at RIKEN Center for Integrative Medical Sciences in Yokohama, Japan, tested the effects of AceCel, which delivers acetate to the lower intestine, on metabolism and obesity in mice.

Burning fat

The researchers compared AceCel to sodium acetate, which is absorbed earlier during digestion and affects the bloodstream more directly. Unlike sodium acetate, AceCel stayed in the gut and led to higher levels of certain beneficial compounds. It also suppressed weight gain, reduced fat mass, and improved blood sugar levels—without causing muscle loss or reduced appetite. 

AceCel triggered the body to burn more fat and activated genes in the liver and fat tissue that are involved in fat breakdown and energy use, the researchers found. These benefits were specific to AceCel and not seen with other similar compounds.

Further experiments showed that AceCel helps the body switch from burning carbohydrates to burning fat, especially during rest or fasting. It does this by activating genes that promote fat breakdown and reducing sugar absorption in the intestine.

Therapeutic strategy

The beneficial effects of AceCel rely on changes in gut bacteria, the team found. AceCel increased the abundance of helpful bacteria such as Bacteroides caccae and Akkermansia muciniphila, which have been linked to metabolic health. 

When tested in germ-free mice or mice with only specific gut bacteria, AceCel only worked in those with Bacteroides, indicating that its benefits depend on these microbes. The key player appears to be a gut bacterium called Bacteroides thetaiotaomicron, which thrives when acetate is present. 

The authors caution that more research is needed to fully understand how acetate and gut bacteria interact, especially in humans. However, they add, “these findings highlight the potential of AceCel as a prebiotic that regulates carbohydrate metabolism in both bacteria and host, offering promise as a therapeutic strategy for obesity.”

What this research adds
Researchers analyzed the effects of a high-fat diet on mice colonized with Fusimonas intestini, a commensal bacterium found in both people and mice with obesity and high blood sugar levels. The team discovered that F. intestini produces long-chain fatty acids such as elaidate, which have been associated with obesity and insulin resistance. F. intestini appeared to impair the integrity of the gut barrier and promote low-grade inflammation. A high-fat diet altered the expression of microbial genes involved in lipid production, including FadR, a master regulator of fatty acid production. Mice colonized with Escherichia coli bacteria expressing FadR had more severe obesity compared to controls.

Conclusions
The findings indicate that gut commensals may contribute to obesity through the overproduction of microbe-derived lipids.

Obesity and diabetes are on the rise, with high fat intake being a major cause of these and other metabolic conditions. Now, researchers have found that specific gut microbes producing long-chain fatty acids can exacerbate diet-induced obesity by compromising the integrity of the gut barrier.

The findings, published in Cell Metabolism, indicate that gut commensals may contribute to obesity through the overproduction of microbe-derived lipids.

Scientists have known that gut bacteria and their metabolites can play a part in the progression of obesity and associated disorders such as diabetes. But how microbial metabolites promote these conditions remains poorly understood.

To address this question, researchers led by Hiroshi Ohno at the RIKEN Center for Integrative Medical Sciences analyzed the effects of a high-fat diet on mice colonized with Fusimonas intestini, a commensal bacterium that the team had previously isolated from mice with high blood sugar levels.

Fat production

The researchers found that F. intestini was also common in people with type 2 diabetes compared with non-obese individuals and those with normal blood sugar levels. More than 70% of people with diabetes harbored F. intestini, whereas only about 29% of controls did.

Mice colonized with F. intestini showed increased cholesterol levels in their blood as well as upregulated immune molecules that are hallmarks of low-grade inflammation and insulin resistance in fat tissues. 

Further tests showed that F. intestini produces long-chain fatty acids including elaidate and palmitate. Both molecules have been implicated in obesity and insulin resistance. In particular, elaidate has been regulated by the US drug regulator due to its link to cardiovascular diseases. 

“Since increased elaidate and palmitate were observed only when [a high-fat diet] was provided together with [F. intestini], we speculated that [F. intestini] might mediate the production of fatty acids that are harmful to host metabolism in response to dietary fat,” the researchers say.

Gut barrier

The high-fat diet altered the expression of microbial genes involved in lipid production, including FadR, a master regulator of fatty acid production, the researchers found. Indeed, mice colonized with Escherichia coli bacteria expressing FadR had more severe obesity compared to controls.

“These findings indicate that microbial functions involving fatty acid biosynthesis impact host metabolism to exacerbate obesity,” the researchers say.

In particular, F. intestini appeared to alter the integrity of the gut barrier through the production of long-chain fatty acids. Intestinal barrier impairment has been tied to obesity and type 2 diabetes through a form of low-grade inflammation called metabolic endotoxemia.

“Given that the expression of genes in gut microbes involved in fatty acid biosynthesis impacts host metabolism, we believe that further understanding of the microbial functions to produce, convert, and metabolize fatty acids in the intestine could open new therapeutic opportunities for obesity,” the researchers say.

What this research adds
Working in mice, researchers found that a diet based on casein, a protein that is commonly found in milk, protects diabetic animals by improving the function of insulin-producing cells. However, gluten — a protein found in certain cereal grains — as well as microbes such as Enterococcus faecalis, which produce specific enzymes that can break down gluten, were able to reverse casein-mediated protection. Breaking down gluten activated the immune system and increased inflammation in the pancreas.

Conclusions
The findings may inform dietary interventions to help protect people against type 1 diabetes and other autoimmune diseases.

Type 1 diabetes is an autoimmune disease in which the pancreas produces little or no insulin — the hormone that controls glucose levels in the blood. Now, researchers have found that some components of the gut microbiota can reverse the beneficial effects of dietary interventions that protect mice against type 1 diabetes.

The findings, published in Cell Host & Microbe, may inform strategies to help protect people against type 1 diabetes and other autoimmune diseases.

Previous studies in animal models have suggested that diet can influence the type 1 diabetes — perhaps through the microbiota. However, whether dietary interventions are mediated by gut microbes remains unclear. 

To address this question, Alexander Chervonsky at the University of Chicago and his colleagues study diet-microbiota interactions in a mouse model of type 1 diabetes.

Diabetes protection

The researchers fed mice a diet containing hydrolyzed casein, a protein that is commonly found in milk, as the only source of amino acids. This diet has been previously reported to protect diabetes-prone mice and rats from the condition.

The team found that hydrolyzed casein protected mice from type 1 diabetes also in the absence of the microbiota. Diabetes-prone mice on the hydrolyzed casein diet responded to glucose slower than mice on a standard diet. Hydrolyzed casein appeared to boost insulin secretion by reducing the stress of beta cells, a type of cells that make insulin and that are typically found in the pancreas in clusters known as islets.

“We suggest that the potential mechanism of protection by [hydrolyzed casein] diet is the reduction of intrinsic damage to the islets caused by cellular stress resulting in a reduction in the overall damage caused by autoimmunity and the prevention or postponement of hyperglycemia,” the researchers say.

Reversing benefits

When the researchers added gluten — a protein found in certain cereal grains — to the hydrolyzed casein diet, mice with an intact microbiota were no longer protected from diabetes, but germ-free mice were. 

Further experiments revealed that microbes such as Enterococcus faecalis, which produce specific enzymes that can break down gluten, were able to reverse casein-mediated protection from diabetes. Breaking down gluten activated the mice’s immune system and increased inflammation in the pancreas, the researchers found.

The results suggest that dietary components such as gluten require processing by the members of the microbiota to trigger autoimmune reactions. “Whether other proteins can utilize similar mechanisms (overcoming positive effects of milk proteins or on their own) is very important,” the researchers say. “We expect our findings to lead to new approaches to protection from autoimmunity and inflammation.”

What this research adds
Researchers used a specific technique that can label both dietary cholesterol and the gut microbes that interact with it. Working in mice, the team found that some gut bacteria can use cholesterol from the diet to generate a molecule called cholesterol sulfate, which has many important roles in the human body, including stabilizing the cell membrane. They also found that Bacterioides can convert cholesterol into cholesterol sulfate.

Conclusions
The findings suggest that Bacteroides can metabolize cholesterol, thus helping to regulate its levels in the blood. Identifying associations between gut microbes and cholesterol can help investigate diet-microbiota interactions in multiple systems.

Cholesterol is a fatty substance found in the blood that helps the body to build healthy cells, but high levels of cholesterol can increase a person’s risk of heart disease. New research now shows that some gut bacteria can metabolize cholesterol, thus helping to regulate its levels in the blood.

The study, published in Nature Microbiology, “opens the door for thinking about whether the microbiome, or specific microbes, can remove cholesterol from circulation,” says senior author Elizabeth Johnson at Cornell University.

Cholesterol can be acquired through the diet or generated in the liver. During digestion, the bile secretes cholesterol into the gut, and gut microbes are thought to influence both bile acid synthesis and biliary cholesterol secretion. The gut microbiota has also been shown to modulate low-density lipoprotein cholesterol (LDL), sometimes called ‘bad’ cholesterol. However, how cholesterol interacts with the gut microbiota has remained unclear.

To address this question, Johnson and her colleagues used a specific technique that can label both dietary cholesterol and the gut microbes that interact with it. The technique, called bio-orthogonal labelling sort sequence spectrometry (BOSSS), was previously developed in Johnson’s lab.

Identifying microbes

The researchers fed labeled cholesterol to mice and then detected cholesterol-interacting gut microbes by their fluorescence. After that, they isolated those bacteria from bacteria that did not interact with cholesterol. Then, DNA sequencing identified the gut microbes associated with cholesterol, and a metabolomic analysis of the isolated microbiota samples revealed which molecules were made when bacteria interacted with cholesterol.

Bifidobacterium pseudolongum and bacteria from the genera Clostridium, Parabacteroides, Oscillospira and Turicibacter were the most common cholesterol-interacting microbes, the researchers found.

The metabolomic analysis showed that gut bacteria can use cholesterol from the diet to generate a molecule called cholesterol sulfate, which has many important roles in the human body, including stabilizing the cell membrane.

Metabolizing cholesterol

The sequencing analysis indicated that Bacteroides microbes were responsible for producing cholesterol sulfate from cholesterol. To confirm this finding, the researchers colonized germ-free mice with Bacteroides strains that lacked an enzyme needed to convert cholesterol into cholesterol sulfate. The gut microbiotas of these mice did not produce cholesterol sulfate, whereas the microbiotas of germ-free mice that were colonized with normal Bacteroides did.

Further analyses showed that the cholesterol sulfate produced by Bacteroides microbes is taken up into blood circulation through the portal vein, a blood vessel that carries blood from the gut and other organs to the liver.
“Overall, these results suggest [cholesterol sulfate] biosynthesis by Bacteroides may modulate the host state via numerous targets that warrant further investigation,” the researchers say. Identifying associations between gut microbes and cholesterol can also help investigate diet-microbiota interactions in multiple systems, they say.

What this research adds
Working in mice, researchers found that two MACs, L-arabinose and sucrose, act together on the gut microbiota, preventing obesity. L-arabinose, which reduces the absorption of sucrose in the gut, seems to increase the levels of bacteria that produce the short-chain fatty acids acetate and propionate, while sucrose boosts the production of these molecules.

Conclusions
The findings suggest that each MAC has specific effects on gut microbes that may influence host’s health.

By being resistant to digestion by the host, microbiota-accessible carbohydrates, or MACs, become prebiotics that gut microbes transform into beneficial compounds. New research in mice suggests that each MAC has specific effects on gut microbes that may prevent diet-induced obesity.

The findings, published in Cell Reports, could pave the way for new approaches that use specific MACs to modulate the gut microbiota and improve host’s metabolic function.

“MACs represent the major energy source for specific gut microbes, which ferment MACs into various metabolites, including short-chain fatty acids that can be beneficial to the host and suppress the development of disease,” the researchers say.

Because gut microbes differ in their ability to use MACs as fuel, how these carbohydrates influence the microbiota and thus host’s health may vary. What’s more, little is known about the effects of each MAC on gut microbes and host’s metabolism.

To address this question, a team of researchers led by Yun-Gi Kim at Keio University set out to investigate the effects of two MACs, L-arabinose and sucrose, on obesity and gut microbiota in mice.

L-arabinose is a carbohydrate extracted from plants and is used as a natural sweetener and food additive. It reduces the absorption of sucrose in the gut, lowering sugar levels in the blood after a meal. Recent research has also showed that L-arabinose modulates the gut microbiota composition and eases symptoms of gut inflammation in mice.

Concerted action

The researchers gave sucrose in the presence or absence of L-arabinose to mice that had fasted for 24 hours. Then, they measured the animals’ blood glucose levels 15, 30 and 45 minutes later. Sucrose levels were lower in mice that received L-arabinose compared to those that didn’t. 

Mice on a high-fat diet that received L-arabinose gained less weight and had lower blood cholesterol levels than those that didn’t receive L-arabinose. Dietary supplementation with L-arabinose also improved glucose tolerance, the researchers found. However, L-arabinose had beneficial effects against diet-induced obesity only in the presence of dietary sucrose.

Supplementation with L-arabinose also appeared to have effects on the gut microbiota: it increased the levels of Bacteroides and Bifidobacterium, two types of bacteria that are negatively correlated with body-weight gain.

Anti-obesity effects

To test whether the levels of specific gut microbes were sufficient for the beneficial effects of L-arabinose on obesity, the researchers colonized germ-free mice with Bacteroides acidifaciens, whose levels were increased in response to L-arabinose, or Escherichia coli as a control. Then, they fed the animals a high-fat diet.

Compared to controls, mice colonized with B. acidifaciens gained less weight and had better glucose tolerance when treated with L-arabinose, the researchers found.

Further experiments showed that L-arabinose increased the levels of bacteria that produce the short-chain fatty acids acetate and propionate, while sucrose acted in concert by boosting the production of these molecules. 
“The present study demonstrated that L-arabinose and sucrose cooperatively act on specific bacteria, such as Bacteroides, which in turn synergistically increase the concentrations of acetate and propionate in the intestine and prevent diet-induced obesity,” the researchers say.

What this research adds
Researchers characterized and traced bacterial sphingolipids produced by the gut microbe Bacteroides thetaiotaomicron in mice. The researchers identified a previously unknown bacterial sphingolipid that transits to the colons and livers of mice. In a mouse model of hepatic steatosis — a condition characterized by increased build-up of fat in the liver, sphingolipid production rescued the excessive storage of lipids. Adding this sphingolipid to liver cells reduced the production of fat, the team found.

Conclusions
The findings suggest that the gut microbiota could contribute to liver function through the transfer of bacterial sphingolipids to the host’s liver.

Metabolites produced by the gut microbiota can contribute to host health and disease, but their effects in specific tissues remain elusive. Now, researchers have found that a specific class of lipids can modulate liver metabolism in mice.

The findings, published in Cell Host & Microbe, suggest that the gut microbiota could contribute to liver function through the transfer of bacterial lipids to the host’s liver.

Bioactive sphingolipids (SLs) are produced by Bacteroides and Prevotella bacteria and have been implicated in immune system modulation and decreased intestinal inflammation. But although it is known that bacterial sphingolipids can alter SL levels in the liver, the effects of bacterial sphingolipids on liver health are unclear.

To address this question, Elizabeth Johnson at Cornell University and her colleagues developed a method to characterize and trace bacterial sphingolipids produced by the gut microbe Bacteroides thetaiotaomicron in mice.

Bacteria-derived lipids

The researchers identified a previously unknown bacterial sphingolipid that transits to the colons and livers of mice. The transfer was not observed using a strain of B. thetaiotaomicron that is unable to produce sphingolipids, the researchers found.

“Despite extensive efforts to characterize other B. thetaiotaomicron-derived lipids that transit to the liver, thus far, our methods have detected only this specific candidate SL,” the researchers say. However, they note, other derivatives of bacterial SLs likely transit to host tissues.

Further analyses showed that the metabolism of fatty acids — the building blocks of fat in the body — was altered in mice with a sphingolipid-producing microbiota. Adding the B. thetaiotaomicron-derived sphingolipid to liver cells reduced the production of fat by improving respiration in cells incubated with excess sugar.

Fat build-up

Next, the team set out to monitor lipid-dependent metabolic effects in the liver. To do so, they fed mice a fat-free diet for two weeks. This diet results in excess storage of fat in the liver and the onset of hepatic steatosis — a condition characterized by increased build-up of fat in the liver.

Sphingolipid production rescued the excessive storage of lipids in mice with hepatic steatosis. Rodents with a sphingolipid-producing microbiota also showed higher expression of genes involved in lipid metabolism.

“Our metabolomic and gene expression data from hepatocytes and mouse livers suggest that the transfer of lipids from sphingolipid-producing bacteria may, directly and indirectly, decrease hepatic lipid accumulation induced by a fat-free diet,” the researchers say.

The findings may help to develop dietary approaches or drugs to target bacterial sphingolipid metabolism for therapeutic use, they add.