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Short-Term Antibiotic Treatment Has No Major Effects on Metabolism

Some scientists believe that an imbalance in gut microbiota — the bacteria that live in the gut — may contribute to obesity and metabolic disease.

However, human evidence is limited and mostly based on observational studies.

A recent randomized controlled trial examined the effects of an antibiotic treatment on gut microbiota and metabolism in obese adults.

Below is a detailed summary of their findings.

Short-Term Antibiotic Treatment

Background

Growing evidence suggests that the bacteria living in your gut may affect your health in a number of ways. They may even play a role in chronic disorders, such as obesity and type 2 diabetes.

Several factors determine what types of bacteria thrive in your gut. These include:

  • Dietary composition: Gut bacteria depend on what and how much you eat. For example, by eating a lot of fiber you help sustain the good bacteria that live in your gut.
  • Antibiotics: Using antibiotics may drastically change your gut microbiota. Broad-spectrum antibiotics are the worst. Observational studies have linked antibiotic use with weight gain, especially early in life.

When potentially harmful bacteria overpopulate the gut and beneficial bacteria are lacking, it is often referred to as dysbiosis.

Observational studies and animal experiments have associated dysbiosis with a variety of metabolic disorders, inflammation and obesity. However, evidence from human studies is limited.

Likewise, strong evidence regarding the effects of antibiotics on metabolism in humans is lacking.

Article Reviewed

This study examined the effects of a 7-day antibiotic treatment on metabolism in overweight and obese men.

Effects of Gut Microbiota Manipulation by Antibiotics on Host Metabolism in Obese Humans: A Randomized Double-Blind Placebo-Controlled Trial.

Study Design

This was a randomized controlled trial examining the effects of antibiotics on gut microbiota and metabolism in obese people.

The researchers recruited 57 overweight and obese, pre-diabetic men who were randomly assigned to receive one of two 7-day antibiotic treatments or a placebo:

  • Amoxicillin: 1,500 mg/day of amoxicillin, a broad-spectrum antibiotic.
  • Vancomycin: 1,500 mg/day of vancomycin, a narrow-spectrum antibiotic that acts against gram-positive bacteria.
  • Placebo: 1,500 mg/day of microcrystalline cellulose (a complex carb) without any antibacterial activity.

At the start and end of each 7-day treatment, the researchers measured the following:

  • Gut bacteria composition: The composition and diversity of gut microbiota was assessed by analyzing genetic material in fecal samples.
  • Insulin sensitivity: Whole-body insulin sensitivity, as well as insulin sensitivity in liver and fat tissue, was analyzed using a number of different methods.
  • Inflammatory markers: Inflammation was assessed by measuring the circulating levels of inflammatory markers — interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α).
  • Gut permeability: Several methods were used to assess gut permeability.
  • Size of fat cells: Abdominal skin fat biopsies were taken to measure the size of fat cells.
  • Calorie expenditure: Calorie expenditure and macronutrient oxidation was measured using indirect calorimetry.
  • Short-chain fatty acids (SCFAs): Levels of SCFAs were measured in blood and fecal samples.
  • Secondary bile acids (SBAs): SBAs were analyzed in blood and fecal samples.

Most of the measurements were conducted after a 10-hour, overnight fast.

To find out if the any of the effects were sustained in the long-term, the researchers measured calorie expenditure, fat cell size and insulin sensitivity two months after the antibiotic treatment ended.

Bottom Line: This was a 7-day randomized controlled trial examining the effects of two antibiotics — amoxicillin and vancomycin — on various metabolic factors in obese, prediabetic men.

Finding 1: Vancomycin Decreased Bacterial Diversity

The study showed that using vancomycin significantly decreased bacterial diversity, compared to a placebo. In contrast, amoxicillin had no significant effects.

Vancomycin had the strongest effects on bacteria in the Firmicutes group, which is involved in short-chain fatty acid formation and the metabolism of bile acids.

Other groups of bacteria increased in abundance, including the vancomycin-resistantLactobacillus plantarum and Enterococcus.

Similar changes have been observed in previous studies examining the effects of antibiotics on gut microbiota.

The present study showed that many of these changes in the gut microbiota were sustained for at least 2 months after the antibiotic treatment ended.

Bottom Line: Vancomycin significantly decreased bacterial diversity, while amoxicillin had no significant effects.

Finding 2: Antibiotics Didn’t Affect Insulin Sensitivity

Insulin sensitivity is a measure of the sensitivity of cells to insulin.

In healthy people, insulin tells the body to clear sugar from the blood. In people with poor blood sugar control, such as diabetics, the body’s cells do not respond efficiently to insulin and blood sugar levels tend to remain high after a meal.

This phenomenon is known as insulin resistance or low insulin sensitivity.

This study showed that a 7-day antibiotic treatment did not affect insulin sensitivity.

These results are supported by a previous study in lean men showing that a broad-spectrum antibiotic treatment did not affect blood sugar control (6).

However, the findings contrast one study in obese people showing that vancomycin reduced insulin sensitivity by 4% in some of the participants. However, the decrease was modest, and the study didn’t include a control group (4).

Bottom Line: An antibiotic treatment with vancomycin or amoxicillin did not affect insulin sensitivity.

Finding 3: Antibiotics Didn’t Affect Calorie Expenditure or Body Weight

Antibiotic TreatmentThe antibiotic treatment did not affect calorie expenditure, fat oxidation or carb oxidation after a mixed, high-fat meal.

Additionally, body weight and fat cell size remained unchanged during the antibiotic treatment and for the duration of the 2-month follow-up period.

In contrast, previous animal studies show that gut microbiota may play a role in calorie absorption and body weight (7, 8).

The antibiotic dose might need to be higher or the treatment length longer to significantly affect body weight or calorie expenditure.

Two studies in endocarditis patients suggested that a 4–6 week treatment using a combination of different antibiotics and higher doses increased body weight (9, 10).

However, the current study strongly suggests that a short-term, 7-day antibiotic treatment with amoxicillin or vancomycin has no such effects.

Bottom Line: A 7-day antibiotic treatment did not affect calorie expenditure or body weight.

Finding 4: Antibiotics Didn’t Cause Inflammation

The researchers measured three inflammatory markers — interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α).

The circulating levels of these markers were unchanged during the antibiotic treatment.

Yet, there was a significant increase in the number of bacteria (Proteobacteria) that may potentially increase inflammation.

Bottom Line: A short-term antibiotic treatment did not affect the circulating levels of the inflammatory markers IL-6, IL-8 and TNF-α.

Finding 5: Antibiotics Didn’t Affect Gut Permeability

Intestinal permeability is a function of the gut wall, allowing nutrients to pass across the gut barrier and into the blood circulation.

When the gut wall is inflamed or weakened, intestinal permeability may be greater than usual. This may allow potentially harmful compounds to “leak” into the blood and cause systemic inflammation.

In fact, intestinal permeability is often assessed by measuring the circulating levels of endotoxins, which originate in the membranes of gram-negative gut bacteria.

This study showed that a 7-day antibiotic treatment with amoxicillin or vancomycin did not affect circulating endotoxin levels, suggesting that it doesn’t affect intestinal permeability.

Bottom Line: A 7-day antibiotic treatment didn’t increase circulating endotoxin levels, indicating that gut permeability remained unaffected.

Finding 6: Vancomycin Reduced Secondary Bile Acids

The liver plays an important role in digestion.

Not only does it store and process nutrients after they have been absorbed, it also produces bile – a liquid that’s essential in the digestion of fat.

Bile works by breaking fat into tiny droplets, known as micelles, allowing it to be absorbed into the bloodstream.

The bile is mainly composed of water and bile acids (bile salts). Most of the bile acids that enter the digestive tract are recycled, meaning they are absorbed and transported back to the liver and used to produce more bile.

A fraction of the bile acids pass down to the colon where they are changed (dehydroxylated by bacterial enzymes) into secondary bile acids (SBAs). SBAs are either absorbed or excreted in the feces.

High levels of SBAs are associated with high fat intake and have been implicated in the development of colon cancer.

The present study showed that vancomycin treatment reduced the levels of SBAs in feces and blood. This was accompanied by reductions in several groups of bacteria that are responsible for producing SBAs.

The health relevance of these findings is unclear.

Bottom Line: Vancomycin treatment reduced the levels of secondary bile acids, which have been associated with an increased risk of colon cancer.

Finding 7: Vancomycin Reduced the Formation of Short-Chain Fatty Acids

Certain types of beneficial gut bacteria in the Firmicutes group produce short-chain fatty acids (SCFAs), such as propionate, butyrate and acetate.

SCFAs are believed to have many health benefits. They nourish the cells lining the colon, may reduce appetite and food intake and have been associated with a reduced risk of colon cancer.

Vancomycin led to a decrease in these SCFA-producing bacteria. Accordingly, levels of butyrate and acetate were significantly lower in the fecal samples of those who were treated with vancomycin, while amoxicillin had no effects.

Similarly, circulating levels of butyrate tended to decrease in response to a vancomycin treatment.

Bottom Line: Treatment with vancomycin, but not amoxicillin, significantly reduced the formation of short-chain fatty acids – butyrate and acetate – in the colon.

Limitations

Although the study’s design appears to be excellent, the findings cannot be generalized to all antibiotics or treatments.

Only two types of antibiotics were tested. Other types of antibiotics or higher doses might have different effects.

Additionally, a longer antibiotic treatment could have given different results, and the findings do not necessarily apply to women or lean, healthy men.

Summary and Real-Life Application

This study showed that a 7-day antibiotic treatment with vancomycin caused significant changes in gut microbiota, while amoxicillin had no significant effects.

Vancomycin also significantly reduced levels of short-chain fatty acids and secondary bile acids in the colon, but the health relevance of these changes is unclear.

The antibiotics didn’t affect markers of inflammation, insulin sensitivity, gut permeability or other metabolic factors.

Simply put, short-term antibiotic treatment with amoxicillin or vancomycin doesn’t seem to affect any major risk factors for obesity, heart disease or type 2 diabetes.

However, before we can make strong conclusions about the health effects of antibiotics, longer studies testing different doses and types of antibiotics are needed.

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