Researchers have successfully tweaked a specialized compound from brown seaweed that appears to hold powerful anti-obesity potential – not through appetite suppression or fat burning, but by targeting the gut microbiome to get your body to fight weight gain naturally and long-term, without drugs or diet changes.
In a study out of Zhejiang University of Technology, scientists extracted fucoidan, a sugar-rich sulfated polysaccharide found in Saccharina japonica, also known as sweet kelp – a type of edible brown seaweed used widely throughout Japan and Korea. While fucoidans – which are found throughout brown algae species – is known for its antioxidant, anti-inflammatory, and immune-system-regulating properties, it's proven difficult for scientists to pry out its full bioactive potential.
Investigating whether they could make fucoidan more bioavailable and therefore biologically impactful, the researchers chemically broke it down into smaller fragments with varying molecular weights and sulfate content, producing four low molecular weight fucoidans (LMWFs). A lower molecular weight means it can interact with the gut's flora much better than larger, complex polysaccharides, which are generally not well broken down by microbial enzymes.
Of the four candidates, one known as LMWF4 stood out. This engineered compound had both the lowest molecular weight and the highest level of sulfation. Lowering the molecular weight made the compound easier for the body to absorb and interact with, while increasing the number of sulfate groups enhanced the molecule's ability to influence gut bacteria.
Essentially, by making fucoidan smaller and more chemically active, the researchers turned a naturally beneficial compound into a targeted gut-regulating tool that didn't just pass through the digestive system but was able to play a role in its makeup that supported metabolic health.
"The structural differences in LMWFs can significantly influence its regulatory effects on gut microbiota and its impact on obesity outcomes," the researchers wrote. "We utilized fucoidan and its four derivatives, each characterized by varying molecular weights and degrees of sulfation, in mouse experiments."
As noted, LMWF4 had a very low molecular weight (mW) of 2.6 kilodalton (kDa), high sulfation (37.7%) and high fucose content (92.9%) – essentially retaining all the good parts of fucoidan but engineered in a way that enabled the gut to reap the benefits it can't otherwise do naturally.
In the study on mice, the animals were split into groups and fed either a low-fat diet (LFD) as the control group, or a high-fat diet (HFD) to model diet-driven obesity. The LFD mice served as the healthy baseline for what regular weight, metabolic health and gut microbiota would look like on a "normal" mouse diet. The real test, though, was among the high-fat diet mice.
After four weeks on the HFD, these mice were then split into groups again – one cohort continued without any intervention, another received natural (crude) fucoidan, extracted directly from brown seaweed, and the remaining animals were each given one of the four LMWFs. After another four weeks, the researchers measured the HFD animals' weight gain, fat accumulation, blood glucose levels and cholesterol, and analyzed their gut microbiota.
What they found was that all fucoidan-treated mice gained less weight than the animals on the HFD and no intervention. But the most dramatic effects came from LMWF4, which not only reduced weight gain and fat buildup but also improved blood sugar and cholesterol levels. They also had a healthier balance of gut bacteria, increasing the abundance of microbes linked to better metabolic health and reducing those associated with obesity.
This suggested that LMWF4 was able to move the gut ecosystem in a way that helps the body resist weight gain – even when exposed to a diet high in fat. In fact, LMWF4 restored the gut's diversity of flora, increasing species richness to near-normal levels. Specifically, this molecule saw an increase in Akkermansia species, known to help protect against obesity, as well as boosts in the levels of genera Blautia and Eubacterium, plus the Muribaculaceae family, which boost short-chain fatty acid (SCFA) production. This too is a marker for improved metabolic health.
Importantly, there was also a drop in numbers of a yet-to-be-classified collection known as the Rikenellaceae_RC9_gut_group, which has been associated with inflammation and obesity-related microbiome shifts in mice. The populations are generally increased through HFDs. Helicobacter species, linked to inflammation and obesity, were also decreased.
Overall, the changes in the mice weren't due to any direct effect on fat metabolism, but what was happening among the microbes. Using DNA sequencing of microbial communities, the team found that LMWF4 reshaped the gut flora to increase the abundance of these beneficial bacteria, while at the same time suppressing those linked to obesity. The results suggested that LMWF4 was able to somehow reprogram the gut environment in a way that made the body more resistant to weight gain and metabolic dysfunction.
While, of course, a key limitation to the study is that it's on mice, however, the results hint that instead of trying to force the body to shed weight with medication or restriction, it might be possible to achieve the same goals by promoting the right fat-fighting microbial army.
And because LMWF4 is derived from a safe, edible source – as kombu, it's often eaten as a cold, pickled dish or dried for a snack or umami-rich stock – it could be developed into a functional food ingredient or supplement for long-term gut-friendly health.
"The analysis of the structural characteristics of different fucoidan, along with the corresponding changes in gut bacteria, provides valuable insights into their influence on the gut microbiota and establishes a foundation for further development of fucoidan-based therapies," the researchers added.
There's a growing body of research supporting the health properties of fucoidans, which are found in the cell walls of brown seaweeds. In a 2024 study looking at fucoidan extracted from Sargassum binderi (Malaysian seaweed), researchers found that rats fed this compound had 36% less weight gain and 18% lower visceral fat compared to untreated animals on a HFD. In 2022, S. japonica (formerly known as Laminaria japonica) fucoidan investigated how the compound improved the fat and blood-sugar profiles of mice that had been treated with antibiotics, hinting at its beneficial interaction with gut flora. And last year, scientists found that crude polysaccharides (including fucoidan) from Sargassum thunbergii had fat-inhibitory effects.
While further studies are needed in humans, this new research opens the door to a new kind of natural obesity treatment that could make the gut resistant to weight gain – and also promote weight loss – long-term. And it shows that not all fucoidans are created equal, and could be "bio-hacked" to better target the microbiome.
"Investigations into the intestinal microbiota at both the phylum and species levels revealed that the administration of the polysaccharide LMWF4 via gavage can mitigate the HFD-induced decrease in the overall quantity and diversity of intestinal flora," the researchers added. "Our discovery indicates that modifications characterized by relatively low Mw and a high sulfation degree exhibit a more pronounced anti-obesity effect. Additionally, these modifications demonstrate a greater capacity to regulate intestinal flora disorders, thereby presenting a potential candidate for anti-obesity treatment."
The research was published in the journal Carbohydrate Polymers.
Source: Zhejiang University of Technology via ScienceDirect
