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Probiotic powers genes to relieve constipation, without upsetting gut

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Probiotic powers genes to relieve constipation, without upsetting gut

At any given time, as many as four million Americans are suffering through bouts of constipation, which has many causes but can also prove stubborn to relieve and hugely impact daily life.

Functional constipation (FC) is characterized by recurrent infrequent stools, or difficulty passing those, and is associated with many serious health conditions such as including cardiovascular disease, Parkinson’s and colorectal cancer.

Constipation also has somewhat of a double-whammy effect on the gut. If there’s already a good-bacteria imbalance, it can further strip away beneficial microorganisms – or probiotics – which are crucial for gastrointestinal health. Laxatives, commonly used to relieve the condition, can deplete this healthy population even further.

Now, scientists have found a way to kickstart gut motility without stripping the delicate gut microbiome of its all-important microbial diversity and balance – by using a specific strain of probiotic sourced from the gut itself.

Researchers from Jiangnan University, Hainan University and the University of Hong Kong found that the gut probiotic Bifidobacteria longum, which aids food breakdown and inhibits inflammation, can be harnessed to relieve constipation. Zooming in, the scientists found that certain strains of B. longum contain the abfA gene cluster, which was able to utilize arabinan – a common plant polysaccharide that’s generally indigestible for humans and difficult for the gut’s bacteria to make use of.

Previously, B. longum has been found to reduce weight gain, insulin resistance and systolic blood pressure.

“We established the causal link between a genetic variant – the abfA cluster – to the key functional difference of probiotic B. longum in multiple model organisms, including mice and humans, and provided mechanistic and ecological insights into how a single gene cluster can affect the gut motility of hosts through arabinan metabolism,” said senior author Qixiao Zhai of Jiangnan University.

The findings come after isolating 185 B. longum strains from 354 participants, from infants to older adults aged 108 years. Through this, the abfA genetic factor became clear.

When constipated mice were given B. longum without the abfA cluster, it did not have any effect on relieving the animals. Similarly, the scientists were able to predict the incidence of constipation in a cohort of humans, based solely on the abundance of abfA in their microbiome – even when the gene cluster was found among other bacteria, not B. longum.

Testing their hypothesis further, the researchers conducted a human trial, with one cohort supplemented with abFa-cluster-carrying B. longum, and another with abFa-deficient B. longum. The results found that the abFA supplementation boosted how the bacteria made use of arabinan, increased beneficial gut metabolites and relieved constipation.

Importantly, the pros did not come with the cons often accompanying constipation relief, such as a decrease in healthy gut bugs – something prevalent in laxative use.

The findings also show that a probiotic alone may not provide the same benefits from one person to another, due to the unique makeup of the individual gut microbiome.

“Probiotic strains were often effective in animal models yet failed in human clinical trials or were poorly validated in humans,” said Jiachao Zhang of Hainan University. “Proof-of-concept studies based on a human cohort in combination with evidence from animal studies are urgently needed for translational research.”

Here, the abfA cluster has been found to be a key target for treatment of constipation in humans, which completely changed how effective B. longum was when tested on human subjects.

“Collectively, this study identified and systematically characterized a key genetic factor responsible for arabinan utilization that addressed one critical challenge in the probiotic field, namely widespread yet unknown strain specificity in probiotic treatment efficacy,” said Shi Huang of the University of Hong Kong.

As well as providing a path to developing more broad spectrum, effective probiotics for gut health, the scientists believe the key abfA cluster itself may be a vital clue in the prevalence and diagnosis of gut problems beyond constipation.

“The abfA cluster is so prevalent in the gut microbiota that it can be developed as a simple yet powerful biomarker for gastrointestinal diseases,” Huang added.

The research was published in the journal Cell Host & Microbe.

Source: University of Hong Kong via Scimex



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