Do you know anyone who drinks a lot of diet sodas and just cannot seem to lose weight? It has been known for some time that these artificial, no-calorie sweeteners not only do not encourage weight loss but may actually promote weight gain and even diabetes by continuously stimulating our desire to taste sweetness. When they were invented by the food industry, these new-to-nature molecules promised to offer a positive option to sugar. They seemed to be a healthier alternative that promised to change our habits and health risks from drinking the high fructose, sugary soft drinks that have defined American billboard culture since the 1950s. However, there are issues.

Sweet foods, it turns out, activate a set of digestive processes, enzymes and hormones like insulin that promote weight gain and diabetes. No-calorie sweet drinks do the same. This is very different from the gut and endocrine response to more bitter or alkaline foods such as vegetables, grains, legumes and other plant-based foods. So despite no calories, these sweeteners have not been so helpful in weight loss as a substitute for the sugary soft drinks. They also are not helpful to diabetics for these same reasons. There is now another reason to suspect that there are other problems with these beverages. It turns out that no-calorie soft drinks change the profile of bacteria in our gut, part of the so-called microbiome. These bacteria, which may in aggregate weigh three to six pounds, constitute one of the largest “organs” in the body. They actually contain about 150 times as much DNA as our human genome. The key issue for our diet is that they are essential to the process of healthy digestion. Many foods, especially plant materials, cannot be adequately metabolized and absorbed without a healthy gut bacterial population. When artificial sweeteners alter this profile, our ability to utilize our food effectively is impaired. We still feel hungry.

In studies of mice, strains that had the genes for obesity could be prevented from gaining weight if they were inoculated with the healthy gut bacteria from lean mice. Likewise, thin mice, if they received the bacteria of obese mice tended to become obese or even diabetic. If the same turns out to be true for humans, as it appears to be, nourishing our healthy gut bacteria may well be one of the pathways to improved weight loss. No-calorie drinks don’t do this.

Taking a probiotic supplement is not as effective in changing our gut bacterial population as is a healthy diet. Foods high in fat and sugar tend to foster a population of Bacteroides strains of bacteria, while a diet higher in fruits, vegetables and fiber, promote bacteria from the Firmicutes class. The latter tend to be better for us in many ways, including protecting us from diabetes, cancer, heart disease and inflammation in general. So don’t count on low calorie or no-calorie beverages to help you lose weight. Eat a Mediterranean style diet or one high in fruits, vegetables and whole grains to nourish healthy gut bacteria in your gut. They may just be your key to weight loss. Also, consider supplementation with high quality probiotics at least three to 20 billion units daily, especially after you have been taking antibiotics for any reason. So what to drink? Here are some low-calorie, no-calorie and more healthful options:

• Water — at least 64 ounces a day for the average, healthy adult;

• Water infused with flavor, such as citrus, cucumber or berries;

• Sparkling water with a twist of lemon or lime, if you wish, maybe with a dash of bitters;

• Tea — green, herbal or black, hot or iced; if you want a sweetener, try raw agave, stevia or raw honey, as these are lower glycemic alternatives;

• Fruit or vegetable juices — avoid those that are high in sugar or sodium content, instead look for high pulp, concentrates, organic types.

Dr. Victor S. Sierpina is the WD and Laura Nell Nicholson Family Professor of Integrative Medicine and Professor of Family Medicine at UTMB.