Study tracks human milk nutrients in infant microbiome

September 1, 2020

Science Daily/Cornell University

A new study in mice helps explain why gut microbiomes of breastfed infants can differ greatly from those of formula-fed infants.

The study, "Dietary Sphinganine Is Selectively Assimilated by Members of the Mammalian Gut Microbiome," was published in July in the Journal of Lipid Research.

Sphinganine from milk Johnson Lab/Provided A new technique allows researchers to track specific nutrients as they are taken up by gut microbes in a mouse's digestive tract. The image shows certain microbes (red) taking in a nutrient common in human milk called sphinganine; blue microbes have not taken it in.

The paper describes an innovative technique developed at Cornell to track the fate of metabolites -- nutrients formed in or necessary for metabolism -- through a mouse's digestive tract and identify how they interact with specific gut microbes.

"We think the methods are expandable to many different microbiome systems," said senior author Elizabeth Johnson, assistant professor of nutritional sciences in the College of Agriculture and Life Sciences. She noted that researchers investigating effects of a high-fat vs. low-fat diet, or a keto diet, might use the technique to track metabolites.

The methodology could reveal how specific metabolites promote specific bacteria. This could allow nutritionists to prescribe that patients eat foods containing specific metabolites to intentionally change the composition of their microbiomes, Johnson said.

Human milk and many other foods contain a class of lipid metabolites called sphingolipids. Previous research suggested that these metabolites help shape an infant's microbiome, but it was not known if they actually interact with the microbiome.

The study identified two types of gut microbes, Bacteroides and Bifidobacterium, that use sphingolipids for their own metabolism.

While very little is known about the specific roles of gut microbes in human health, Bacteroides have been implicated in both beneficial and not-so-beneficial effects, depending on context. They are generally associated with microbiomes of healthy breastfed infants. Bifidobacterium, shown for the first time in this study to process dietary sphingolipids, are considered the quintessential beneficial bacteria, comprising up to 95% of breastfed infants microbiome.

They're also a highly popular over-the-counter probiotic.

"Our lab is very interested in how the diet interacts with the microbiome in order to really understand how you can best modulate it to have positive effects on health," Johnson said. "In this study, we were able to see that yes, these dietary lipids that are a big part of [breastfed] infants diets, are interacting quite robustly with the gut microbiome."

Sphingolipids originate from three main sources: diet; bacteria that can produce them; and most host tissues.

Johnson, along with first author Min-Ting Lee, a doctoral student, and Henry Le, a postdoctoral researcher, both in Johnson's lab, created a technique to specifically track dietary sphingolipids as they passed through the mouse gut.

"We custom synthesized the sphingolipid we added to the diet," Johnson said. "It is almost identical to ones derived from breast milk but with a small chemical tag so we could trace the location of the sphingolipid once it was ingested by the mice."

Lee then used a fluorescent label that attached to cells or microbes that absorbed the tagged lipid, such that any bacteria that had taken up sphingolipids lit up red. Microbes from the mice's microbiomes were then isolated and analyzed. Populations with red microbes were separated from the others, and these were then genetically sequenced to identify the species of bacteria.

With further investigation, Le was able to identify the metabolites that Bacteroides and Bifidobacterium produce when exposed to dietary sphingolipids. Further investigations are underway to determine whether these microbially-produced metabolites are beneficial for infant health.

Johnson recently received a five-year, $1.9 million Maximizing Investigators' Research Award from the National Institutes of Health (NIH) to expand on this work, to better understand how lipid-dependent host-microbe interactions affect human health..

The study was supported by seed funds from the Genomics Facility of the Biotechnology Resource Center at Cornell's Institute of Biotechnology.

https://www.sciencedaily.com/releases/2020/09/200901142725.htm

Probiotics alone or combined with prebiotics may help ease depression

July 6, 2020

Science Daily/BMJ

Probiotics either taken by themselves or when combined with prebiotics, may help to ease depression, suggests a review of the available evidence, published in BMJ Nutrition Prevention & Health.

But as to whether they might help to lessen anxiety isn't yet clear, say the researchers.

Foods that broaden the profile of helpful bacteria in the gut are collectively known as probiotics, while prebiotics are compounds that help these bacteria to flourish.

In the UK in 2016-17, 1.4 million people were referred with mental health issues, over half of them (53%) had anxiety or stress related disorders, while a third (33%) had depression.

A two-way relationship exists between the brain and digestive tract, known as the gut-brain axis. And the possibility that the microbiome -- the range and number of bacteria resident in the gut -- might help treat mental ill health has become a focus of interest in recent years.

To explore this further, the researchers searched for relevant studies published in English between 2003 and 2019, which looked at the potential therapeutic contribution of pre-and probiotics in adults with depression and/or anxiety disorders.

Out of an initial haul of 71 studies, just 7 met all the criteria for inclusion. All 7 investigated at least 1 probiotic strain; 4 looked at the effect of combinations of multiple strains.

In all, 12 probiotic strains featured in the selected studies, primarily Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium bifidium. One study looked at combined pre-probiotic treatment, while one looked at prebiotic therapy by itself.

The studies varied considerably in their design, methods used, and clinical considerations, but all of them concluded that probiotic supplements either alone or in combination with prebiotics may be linked to measurable reductions in depression.

And every study showed a significant fall or improvement in anxiety symptoms and/or clinically relevant changes in biochemical measures of anxiety and/or depression with probiotic or combined pre-probiotic use.

Of the 12 different probiotics investigated, 11 were potentially useful, the findings showed.

The researchers highlight several caveats to their review: none of the included studies lasted very long; and the number of participants in each was small.

This makes it difficult to draw any firm conclusions about the overall effects, whether they are long lasting, and whether there might be any unwanted side effects associated with prolonged use, they say.

Nevertheless on the basis of the preliminary evidence to date, pre- and probiotic therapy warrant further investigation, they suggest.

Probiotics may help reduce the production of inflammatory chemicals, such as cytokines, as is the case in inflammatory bowel disease, suggest the researchers. Or they may help direct the action of tryptophan, a chemical thought to be important in the gut-brain axis in psychiatric disorders.

As anxiety disorders and depression affect people very differently, they require treatment approaches that take account of these complexities, they say. "In this way, with a better understanding of the mechanisms, probiotics may prove to be a useful tool across a wide range of conditions," they write.

People with depression and/or anxiety disorders also often have other underlying conditions, such as impaired insulin production and irritable bowel syndrome, they point out.

"As such, the effect that probiotics have on patients with [common mental disorders] may be twofold: they may directly improve depression in line with the observed findings of this review, and/or they might beneficially impact a patient's experience of their [common mental disorder] by alleviating additional comorbidities," they write.

"Purely from the information gathered for this review, it is valid to suggest that, for patients with clinically recognised depression: isolate, or adjuvant prebiotic therapy is unlikely to affect an individual's experience of their condition in a quantitatively evident way; and that isolate or adjuvant, probiotic/combined prebiotic-probiotic therapy may offer a quantitatively measurable improvement in parameters relating to depression," they conclude.

"However, there are inadequate data to suggest anything meaningful to support or refute the use of either pre/probiotic agents (or a combination of both) in patients with clinically recognised anxiety disorders; this would be a useful area to investigate further."

https://www.sciencedaily.com/releases/2020/07/200706203820.htm