Could a bacterial supplement help maintain weight loss after dieting?

Overweight and obesity are major risk factors for cardiovascular disease (CVD), the world’s leading cause of death, which was responsible for an estimated 32% of all global deaths in 2022.

Weight loss reduces CVD risk – and even modest reductions can be beneficial. One study found that a 5-10% weight loss was associated with improvements in cardiovascular risk factors.

However, maintaining weight loss is difficult. On average, most people regain 80% of the weight they have lost within five years. Weight regain also occurs after stopping newer pharmacological treatments, including GLP-1 receptor agonists.

A recent systematic review concluded that patients could regain up to nearly 10kg after stopping semaglutide or tirzepatide.

Identifying therapeutic targets that support weight maintenance is therefore important. One potential target is the gut microbiota.

Akkermansia muciniphila

A human’s gut microbiota contains up to 100 trillion microbes, with more than 150-times as many genes as the human genome. Increasing evidence suggests that the gut microbiome has an important role in obesity risk.

In one model of type 2 diabetes (T2D), faecal microbiota transplanted from healthy donors prevented body weight gain in mice with diabetes. One bacterial species, Akkermansia muciniphila (Akk), which is a probiotic, appears to have a role in preventing the development of T2D and obesity.

In an analysis of 15 animal studies, Akk reduced body weight gain by 10.4% and fasting blood glucose by 21.2%. Unlike many gut bacteria, which break down dietary substrates, Akk uses the mucus layer covering the intestinal epithelium as a substrate for carbon, nitrogen and energy.

This Gram-negative anaerobic bacterium is a common resident of the human gut and although animal studies suggested Akk might help prevent weight regain, the first human study was undertaken only in 2016.

Researchers recruited 49 adults with overweight or obesity and placed them on a calorie-reduced diet for six weeks. Analysis of faecal samples showed a relationship between Akk levels and overall health: those with higher Akk abundance were metabolically healthier before and after the dietary intervention.

Although this was of interest, it did not explain the nature of the relationship. That changed in 2019, when 32 overweight or obese insulin-resistant volunteers received a pasteurised Akk supplement for three months. At the end of the study, insulin sensitivity improved by 30% compared with placebo, with small reductions in weight (2.27kg) and hip circumference (2.63cm).

These findings suggested that Akk might support weight loss. However, given the animal data indicating a potential effect on weight regain, a randomised trial was needed to test whether Akk could help prevent regain after dieting.

Small effect

In a recent controlled trial, Mount et al randomised 90 adults with overweight or obesity to an eight-week low-energy diet designed to induce weight loss of more than 8%. This was followed by a 24-week weight maintenance phase, during which participants could eat as they wished and were randomised to receive either Akk supplementation or a matching placebo.

The primary outcome was the change in body weight during the maintenance phase. After 24 weeks, participants taking Akk had gained an average of 1.2kg, compared with 3.2kg in the placebo group.

There was also a slightly greater loss of fat mass among those taking Akk. However, there were no other significant differences between groups in cardiovascular markers, such as fasting lipids. If Akk supplementation does help to prevent weight regain, the study by Mount and colleagues suggests the effect is small, at around 2kg.

Implications for practice

Before recommending Akk products, it is worth considering the latest findings alongside wider evidence on probiotics, synbiotics – combinations of prebiotics and probiotics – and weight loss.

One recent analysis concluded that although probiotics produced significant reductions in body weight, the effect was small, at around 0.91kg. Other studies of Akk have also shown small reductions in weight, but the benefit appears to depend on baseline abundance of the organism.

For example, participants with higher baseline Akk levels showed poor colonisation and no significant clinical effects. Similarly, the recent trial by Mount and colleagues found greater benefits only among those with lower baseline Akk levels.

The current evidence supports a cautious, balanced discussion with patients. Akk supplementation may have a modest effect on weight regain in some people, but further studies are needed to define its clinical value in obesity risk reduction and long-term weight maintenance.

References

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