Some people with obesity have a distinct oral microbiome signature – a discovery that could lead to a way to spot the condition early and potentially prevent it.

The huge community of microbes that resides in the gut can contribute to weight gain and has been strongly and . So far, though, the evidence that the oral microbiome, which houses , is involved in or in has been more limited.

“The oral microbiome is the second largest microbial ecosystem in the human body, so we decided to study whether it is associated with systemic diseases,” says at New York University Abu Dhabi in the United Arab Emirates.

He and his colleagues took saliva samples from 628 Emirati adults, 97 of whom had obesity, and sequenced these to discover which microbes were present. The researchers compared these against 95 individuals from the group who were a healthy weight but were otherwise similar to the people with obesity in terms of age, sex, lifestyle, oral health and frequency of tooth brushing.

The comparison revealed that the oral microbiomes of the people with obesity featured more bacteria that drive inflammation, such as Streptococcus parasanguinis and Actinomyces oris, and more Oribacterium sinus, which produces lactate. Elevated lactate levels are .

Jha and his colleagues also identified 94 differences in microbial metabolic pathways between the two groups. For example, people with obesity had boosted mechanisms for carbohydrate metabolism and the breakdown of an essential amino acid called histidine, but were worse at making B vitamins and heme, which is important for transporting oxygen.

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Metabolites produced in greater numbers by the boosted processes in people with obesity included lactate, histidine derivatives, choline, uridine and uracil. These compounds are associated with indications of metabolic dysfunction, such as higher levels of triglycerides, liver enzymes and glucose in the blood.

“If we put this together, a metabolic pattern emerges. The data point toward a low‑pH, carbohydrate‑rich, inflammatory oral environment in the obese individuals,” says at King’s College London. “This study provides some of the clearest evidence to date that the oral microbiome reflects, and may contribute to, metabolic changes associated with obesity.”

For now, this is only an association, so cause and effect still need to be disentangled. “Some of these associations are mind-blowing to me, but right now, we cannot say anything about what is causing what, so that’s the next step for us,” says Jha.

To disentangle whether it is the oral microbiome causing obesity or it is being changed by the condition, Jha and his colleagues are planning follow-up experiments that look at both saliva and the gut microbiome to see if there is any movement of microbes or metabolites from the mouth to the gut.

Jha thinks that could be possible, but says his hypothesis is that our mouth is full of blood vessels that support our ability to taste and quickly deliver nutrients to where they are needed, and these vessels may also enable metabolites to get straight into our bloodstream and affect the rest of the body.

Establishing causation will also require randomised-controlled trials and studies that dig into the metabolic pathways, says Edwards.

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It could be that, when diet starts to change, some elements of the food can be better metabolised by certain bacteria, which flourish and start producing more metabolites that may influence our cravings for certain foods, pushing people towards the path of obesity, says Jha. Uridine, for example, is known to , he says.

If it does turn out that oral bacteria can drive obesity, it might provide a route for interventions to prevent it, says Edwards, such as transferring healthy oral microbes via a gel, prebiotics that promote the growth of specific bacteria, targeted antimicrobials or pH‑modifying rinses. “No doubt behavioural interventions, such as reducing sugar intake, will also help.”

Even if the oral microbiome is an effect of obesity rather than a cause, assessing it could still be useful. The distinct microbiome shifts could be easily picked up by a saliva test, so could work as a way to detect obesity early to facilitate prevention, says Jha.

A daily pill could soon be available as an alternative to Wegovy and Ozempic injections after a trial found it led to substantial weight loss and improved blood sugar levels in people with obesity and type 2 diabetes.

Orforglipron, developed by pharmaceutical company Eli Lilly, is designed to work in the same way as semaglutide, the active ingredient in Wegovy and Ozempic, which mimics a hormone called GLP-1.

A found that orforglipron enabled people with obesity but without type 2 diabetes to lose about 11 per cent of their body weight, on average, over 72 weeks. This is less than the 15 per cent typically achieved over a similar period , but taking medication as a pill is more convenient, says at the University of Texas.

To explore whether people with obesity and type 2 diabetes could also benefit, she and her colleagues enrolled more than 1600 people with both conditions from 10 countries including India, Australia, China, Germany, Brazil and the US.

They randomly assigned about 900 of the participants to take either a low, medium, or high dose of orforglipron daily. The remaining participants took a daily placebo pill, and they all received lifestyle advice.

After 72 weeks, those on the high dose had lost nearly 10 per cent of their body weight, on average, with 67 per cent of this group losing more than 5 per cent. The medium and low dose groups lost roughly 7 per cent and 5 per cent, on average, while those on the placebo lost less than 3 per cent.

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This confirms that orforglipron causes less weight loss than injectable GLP-1 drugs, but it can still provide benefits for people’s health and quality of life, says at University College London, who wasn’t involved in the study. “Weight loss of just 5 per cent tends to show very clear benefits – for instance, people are able to exercise a bit more, to change their lifestyle, reduce their risk of other conditions,” he says.

People taking the high dose also saw a reduction in their blood sugar levels of nearly 2 per cent, on average, with about 75 per cent of them achieving levels commonly targeted by diabetes patients, says Horn. Smaller benefits were seen with lower doses, and those on the placebo saw their blood sugar levels fall by just 0.1 per cent.

About a tenth of the participants on the high and medium doses had to stop taking the drug due to side effects such as nausea, vomiting and diarrhoea, which was about twice the rate seen in the low-dose and placebo groups. But most participants found the side effects were manageable, says Horn. “Side effects were consistent with other [injectable] GLP-1 medications,” she says.

Eli Lilly is hoping the drug will be approved by the US Food and Drug Administration for treating obesity and type 2 diabetes early next year, says Horn. “It is my hope as a physician that the FDA will choose to approve all three doses so that we have flexibility in choosing the best dose for our patients that optimises health and minimises side effects,” she says.

Orforglipron should be cheaper to make, store and deliver to patients than injectable GLP-1 drugs because it doesn’t require refrigeration or syringes, says Trapp. This, combined with the fact it avoids the discomfort of injections, means it could widen access to GLP-1 weight-loss drugs, which are currently expensive and difficult to access in some lower- and middle-income countries, he says.