High-fat diet with antibiotic use linked to gut inflammation

Combining Western diet and antibiotic use is a pre- IBD risk factor

July 15, 2020

Science Daily/University of California - Davis Health

UC Davis researchers have found that combining a Western-style high-fat diet with antibiotic use significantly increases the risk of developing pre-inflammatory bowel disease (pre-IBD). The study, published July 14 in Cell Host and Microbe, suggests that this combination shuts down the energy factories (mitochondria) in cells of the colon lining, leading to gut inflammation.

Irritable bowel syndrome (IBS) affects approximately 11% of people worldwide. It is characterized by recurring episodes of abdominal pain, bloating and changes in bowel habits. IBS patients with mucosal inflammation and changes in the gut's microbial composition are considered pre-IBD.

Antibiotic usage with high-fat diet is a risk factor

The study included 43 healthy adults and 49 adult patients diagnosed with IBS. The researchers measured fecal calprotectin, a biomarker for intestinal inflammation, of participants. Elevated levels of fecal calprotectin indicated a pre-IBD condition. The study identified 19 patients with IBS as pre-IBD.

The researchers found that all participants who consumed high-fat diet and used antibiotics were at 8.6 times higher risk for having pre-IBD than those on low-fat diet and no recent history of antibiotic use. Participants with the highest fat consumption were about 2.8 times more likely to have pre-IBD than those with the lowest fat intake. A history of recent antibiotic usage alone was associated with 3.9 times higher likelihood of having pre-IBD.

"Our study found that a history of antibiotics in individuals consuming a high-fat diet was associated with the greatest risk for pre-IBD," said Andreas Bäumler, professor of medical microbiology and immunology and lead author on the study. "Until now, we didn't appreciate how different environmental risk factors can synergize to drive the disease."

Shutting the cell's powerhouse promotes gut microbial growth

Using mouse models, the study also tested the effect of high-fat diet and antibiotics use on the cells in the intestinal lining. It found that high-fat diet and antibiotics cooperate to disrupt the work of the cell's mitochondria, shutting its ability to burn oxygen. This disruption causes reduction in cell's oxygen consumption and leads to oxygen leakage into the gut.

The body's beneficial bacteria thrive in environments lacking oxygen such as the large intestine. Higher oxygen levels in the gut promote bacterial imbalances and inflammation. With the disruption in the gut environment, a vicious cycle of replacing the good bacteria with potentially harmful proinflammatory microbes that are more oxygen tolerant begins. This in turn leads to mucosal inflammation linked to pre-IBD conditions.

The study also identified 5-aminosalicylate (mesalazine), a drug that restarts the energy factories in the intestinal lining, as a potential treatment for pre-IBD.

"The best approach to a healthy gut is to get rid of the preferred sustenance of harmful microbes," Lee said. "Our study emphasized the importance of avoiding high fat food and abuse of antibiotics to avoid gut inflammation."

https://www.sciencedaily.com/releases/2020/07/200715142400.htm

Antibiotic use linked to greater risk of heart attack and stroke in women

April 24, 2019

Science Daily/European Society of Cardiology

Women who take antibiotics over a long period of time are at increased risk of heart attack or stroke, according to research carried out in nearly 36,500 women.

The study, published in the European Heart Journal [1] today (Thursday), found that women aged 60 or older who took antibiotics for two months or more had the greatest risk of cardiovascular disease, but long duration of antibiotic use was also associated with an increased risk if taken during middle age (aged 40-59). The researchers could find no increased risk from antibiotic use by younger adults aged between 20-39.

Professor Lu Qi, director of the Tulane University Obesity Research Centre, Tulane University, New Orleans, and adjunct professor of nutrition at Harvard T.C. Chan School of Public Health, Boston, USA, who led the research, says that a possible reason why antibiotic use is linked to an increased risk of cardiovascular disease is because antibiotics alter the balance of the micro-environment in the gut, destroying "good" probiotic bacteria and increasing the prevalence of viruses, bacteria or other micro-organisms that can cause disease.

"Antibiotic use is the most critical factor in altering the balance of microorganisms in the gut. Previous studies have shown a link between alterations in the microbiotic environment of the gut and inflammation and narrowing of the blood vessels, stroke and heart disease," he said.

The researchers studied 36,429 women who took part in the Nurses' Health Study, which has been running in the USA since 1976. The current study looked at data from 2004 to June 2012. In 2004 the women were aged 60 or older, and they were asked about their use of antibiotics when they were young (20-39), middle-aged (40-59) or older (60 and older). The researchers categorised them into four groups: those who had never taken antibiotics, those who had taken them for time periods of less than 15 days, 15 days to two months, or for two months or longer.

During an average follow-up period of nearly eight years, during which time the women continued to complete questionnaires every two years, 1056 participants developed cardiovascular disease.

After adjustments to take account of factors that could affect their results, such as age, race, sex, diet and lifestyle, reasons for antibiotic use, overweight or obesity, other diseases and medication use, the researchers found that women who used antibiotics for periods of two months or longer in late adulthood were 32% more likely to develop cardiovascular disease than women who did not use antibiotics. Women who took antibiotics for longer than two months in middle age had a 28% increased risk compared to women who did not.

These findings mean that among women who take antibiotics for two months or more in late adulthood, six women per 1,000 would develop a cardiovascular disease, compared to three per 1,000 among women who had not taken antibiotics.

The first author of the study is Dr Yoriko Heianza. a research fellow at Tulane University. She said: "By investigating the duration of antibiotic use in various stages of adulthood we have found an association between long-term use in middle age and later life and an increased risk of stroke and heart disease during the following eight years. As these women grew older they were more likely to need more antibiotics, and sometimes for longer periods of time, which suggests a cumulative effect may be the reason for the stronger link in older age between antibiotic use and cardiovascular disease."

The most common reasons for antibiotic use were respiratory infections, urinary tract infections and dental problems.

The study is the largest prospective study to investigate the link between antibiotic use and risk of heart disease and stroke, and this is one of the strengths of the study, as well as the long follow-up and comprehensive information on factors that could affect the results such as life style, diet, age, other diseases and medication use.

Limitations include the fact that the participants reported their use of antibiotics and so this could be mis-remembered. However, as they were all health professionals, they were able to provide more accurate information on medication use than the general population. The researchers did not have information on the different classes of antibiotics used, but believe that the most common type of prescription tends to depend on the infections it is treating, and information on these was included in their analysis. As the study only looked at middle-aged and elderly women, the results cannot necessarily be extrapolated to younger ages and to men.

Prof Qi concluded: "This is an observational study and so it cannot show that antibiotics cause heart disease and stroke, only that there is a link between them. It's possible that women who reported more antibiotic use might be sicker in other ways that we were unable to measure, or there may be other factors that could affect the results that we have not been able take account of.

"Our study suggests that antibiotics should be used only when they are absolutely needed. Considering the potentially cumulative adverse effects, the shorter time of antibiotic use the better."

https://www.sciencedaily.com/releases/2019/04/190424202539.htm

Childhood antibiotics and antacids may be linked to heightened obesity risk

These drugs may alter gut microbes associated with weight gain, say researchers

October 30, 2018

Science Daily/BMJ

Young children prescribed antibiotics and, to a lesser extent, drugs to curb excess stomach acid, may be at heightened risk of obesity, new research suggests.

These drugs, particularly if taken for lengthy periods, may alter gut microbes that have been associated with weight gain, explain the researchers.

The composition of gut bacteria (the microbiome) has been linked to various aspects of human health, including obesity. And certain drugs, such as antibiotics and acid suppressants-histamine 2 receptor antagonists (H2RA) and proton pump inhibitors (PPIs)-can alter the type and volume of bacteria in the gut.

To try and find out if exposure to these drugs in early childhood might increase the risk of obesity, the researchers looked at the medicines prescribed to 333,353 infants, whose medical records had been input into the US Military Health System database between 2006 and 2013, in the first two years of their lives.

In all, 241, 502 (72.5%) had been prescribed an antibiotic; 39,488 (just under 12%) an H2RA; and 11,089 (just over 3%) a PPI during this period. Some 5868 children were prescribed all three types of drug.

Some 46,993 (just over 14%) children became obese, of whom 9628 (11%) had not been prescribed any antibiotics or acid suppressants.

Boys, those born after a caesarean section, and those whose parents were below officer rank were more likely to become obese.

But after taking account of potentially influential factors, a prescription for antibiotics or acid suppressants was associated with a heightened risk of obesity by the age of 3 -- the average age at which obesity was first identified in these children.

A prescription for antibiotics was associated with a 26 per cent heightened risk of obesity. This association persisted, irrespective of antibiotic type, and strengthened with each additional class of antibiotic prescribed.

Acid suppressants were also associated with a heightened obesity risk, although to a lesser extent, and this association strengthened for each 30-day supply prescribed.

Although the largest study of its kind, it is nevertheless observational, and as such, can't establish cause. And potentially influential information on how much the children's mothers weighed, and whether they smoked or had other underlying conditions wasn't available.

And the researchers emphasise that the links between the individual, the environment, and obesity are complex, highlighting the "current difficulty of drawing clear conclusions about the interplay between exposure history, gut microbiota and propensity to develop obesity."

They add: "There is an important therapeutic role for microbiota-altering medications. The long term risks to health must be weighed against the short-term benefits."

But they also point out that over prescription of both antibiotics and acid suppressants, including in young children, is "a significant problem."

https://www.sciencedaily.com/releases/2018/10/181030184507.htm