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Probiotic genomic sequencing research could open new frontiers for dairy products.

It all started with a little bug. A REALLY little bug. It's a bacterium called Lactobacillus acidophilus, if you're a Latin scholar or interested in the taxonomy of microbes. If you're a health-conscious consumer or a curious processor, it's the culture that delivers those mysterious health benefits that the yogurt faithful have attributed to their product for hundreds of years.

Now the focus is on the really tiny components of this really little bug, all the way to the sequence of its DNA and beyond. So significant is the perceived human benefit of L. acidophilus that six organizations, including two university research labs, have joined forces just to pull down its genes, so to speak. They want to find out just what strands of DNA make it tick; how it ticks, and how it makes the immune system and other human systems tick.

Bring on the genes

The advances in genomic research in recent years have been staggering. The recently announced completion--more or less-of the human genomic sequencing project has drawn tremendous attention to this fascinating, limitless and, to some, even frightening area of research. Genomic sequencing penetrates to the core of life itself, into the DNA (deoxyribonucleic acid) that makes up the genes of living organisms and determines the traits they will show and bear. And while L. acidophilus has only about 2,000 genes compared with the estimated 30,000 to 40,000 genes of humans, researchers are, nevertheless, intrigued with the possibilities of the interplay between this microscopic organism and its human host.

"Our goal is to find out which of the genes in Lactobacillus acidophilus is responsible for its health--promoting qualities, which of the genes allow it to survive and enable it to be a probiotic culture," says Bill Haines, vice president of business-to-business marketing for Dairy Management Inc., Rosemont, Ill. "We want to know which of the claimed effects on human health are real and which may make commercial sense."

Each of the organizations involved in this research alliance has a vested interest in the outcome. Dairy farmers, for example, fund DMI and charge the organization to increase the use and consumption of dairy products.

The research may clear the way for the addition of effective probiotics to cheese and other cultured products. Probiotics are consumed by American consumers primarily in the form of yogurt with active cultures and through dietary supplements. Sour cream, cottage cheese, kefir, liquid yogurt and infant formula provide most of the remainder of the probiotic market, although some manufacturers have added probiotic cultures to ice cream and cheese as well. The results of the acidophilus study may also help identify other microorganisms that have the same genes and thus are potential probiotics.

The research will likely give a boost to similar examination of bifido culture, a bacterium found in the gut of infants and commonly used in European functional foods. On the high end, genetic engineers ponder the possibility of transferring the health-producing genes to other organisms to deliver probiotic effect.

Organizations like Southeast Dairy Foods Research Center, North Carolina Dairy Foundation, DMI and California Dairy Research Foundation hope to prove that dairy products are the best ways to deliver the probiotic benefits of acidophilus to consumers. "We think they are," says Haines. "It could be that (dairy products) help the probiotics work in the gut or enhance their function, their natural profile, or help them grow."

Rhodia, the primary funding organization in the alliance, hopes to sell more--and better--products. "We hope the research will lead to more efficacious, more stable probiotic cultures," says Scott Bush, commercial development manager for Rhodia Inc.

North Carolina State University sees the project as an extension of a long tradition of L. acidophilus work. The research focuses specifically on the NCFM strain of L. acidophilus, developed at North Carolina State University in 1972. NCFM, used because of its heartiness and ability to survive, particularly through bioprocessing, was the first acidophilus strain to be used in a sweet milk process.

"Rhodia has really come forward," says Todd Klaen hammer, director of Southeast Dairy Foods Research Center at North Carolina State. "They have spent a lot of money to move the field."

Long life may hinge on long-lived cultures

Stability in probiotic cultures has long been an issue with yogurt consumers and manufacturers alike. The centuries old suspicion that fermented milk products like yogurt increase longevity and improve overall health has been counterbalanced with the fact that many active milk cultures die in storage, in transport or in the intestine before they can do their thing.

Though belief in the healthful effects of probiotic cultures runs strong in the scientific community, validation is far from complete, at least for some of the claims.

"A lot of the work on probiotic cultures is scattered," says Douglas DiRienzo, a researcher with the National Dairy Council. "The work is good, well-established on its help with lactose maldigestion. But its effect on cholesterol, cancer, blood pressure, diarrhea and chronic (ailments) has not been fully established. A lot of the health claims are anecdotal. In some cases, people who consumed (foods with probiotic cultures) just claimed they feel better. Better efficacy work needs to be done.

"There has not been a lot of comprehensive work done on the DNA strands."

One thing is certain: To deliver longer lives to humans, healthful bacteria need longer lives themselves. Rhodia believes the current research will lead to bigger, better lives for probiotic (bacterial) populations.

"Delivering viable bacteria to consumers is still a challenge," says Rhodia's Bush. "Shipping and storage temperatures can be abusive. Our hope is that what we learn will enhance their stability in higher temperatures and for longer storage periods."

At the end of the research lies, also, better under standing of what happens in the GI tract, what goes on to produce the probiotic effect.

"We have found genes that help tolerate acid and bile," explains NCSU's Klaenhammer. "In the end, we will have a catalogue of genes that may impact these criteria."

At the top rung of microbiology

"This organism is very interesting, very adaptive," says Raul Cano, founder and director of the Environmental Biotechnology Institute at California Polytechnic State University. Cano is a microbiologist and molecular biologist and a specialist in the area of functional genomics. His lab gained recognition in 1995 when it isolated living 25 to 35 million-year-old microorganisms from amber. Recently, the lab completed sequencing work on bacteriophage. He knows that this is elitist stuff--"sex of the angels biology," as he calls it.

"Uncovering the DNA sequence is just the first step in understanding what a gene does," says Cano. "A lot of things happen before a gene becomes protein. The project demands skill in recognizing DNA patterns as well as the ability to clone using special systems. Many of the genes go unrecognized. Even serendipity plays a role in what they become."

During the human genome sequencing research, scientists discovered that human beings carry the history of evolution in their genes. It is carried in the so-called "junk" DNA. Lactobacillus is not nearly so complex.

"Lactobacillus seems to build a lasting relationship with other organisms," explains Cano. "It doesn't need to carry all those genes."

"We hope to upgrade strains currently out there. We may look for strains that are already more stable," Bush says. "We may be able to screen strains related to more stability. Or perhaps we will be able to find ways to turn on certain genes to make a culture more stable. Perhaps we can find a way to activate the chain of activity of a gene."

"One of the goals in the genome project is to understand the properties and why L. acidophilus is an effective probiotic," says Klaenhammer. "Sequencing the genetic makeup of acidophilus will help us better understand how the organism works and functions. Once we have knowledge of functionality, we'll be better able to develop strains targeted toward specific conditions."

"We will end up with a better understanding of how lactic bacteria promotes health in humans," says Cal Poly's Cano. "We will have a better functional understanding of them. If lucky, we will be able to identify the key genes that promote human health. And promoting and extending human life is always a goal of science."

"Who knows?" says Haines. "Beyond the host of dairy product benefits, we may discover how to insert the healthful genes into higher-order organisms for better health. Perhaps this is far-fetched ... but you just don't know!"


Probiotics are consumed by U.S. consumers primarily in the form of yogurt with active cultures and through dietary supplements. Sour cream, cottage cheese, kefir, liquid yogurt and infant formula provide most of the remainder of the probiotic market, although some manufacturers have added probiotic cultures to ice cream and cheese as well.
Sales Year  Yogurt sales at
              (in billions)
'96-'97              $1.468
'97-'98              $1.534
'98-'99              $1.637
'99-'00               $1.76
Figures courtesy of Carlos Ayola, Frost
& Sullivan


Probiotic--A live microbial food supplement that affects the host animal beneficially by improving microbial balance in its intestines.

Prebiotic--A non-digestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon.

Synbiotic--A combination of probiotics and prebiotics that beneficially affects the host by improving the survival and the implantation of live microbial dietary supplements in the gastrointestinal tract by selectively stimulating the growth and/or by activating the metabolism of one or a limited number of health-promoting bacteria.


1. Pathogen interference, exclusion and antagonism

2. Immunostimulation and immunomodulation

3. Anticarcinogenic and antimutagenic activities in animal models

4. Alleviation of symptoms of lactose intolerance

5. Vaginal/urinary tract health

6. Reduction in blood pressure in hypertensive subjects

7. Decreased incidence and duration of diarrhea (antibiotic-associated diarrhea, Clostridium difficile, travelers and rotaviral)

8. Maintenance of mucosal integrity

Note: These benefits were identified at a symposium entitled "Probiotic Bacteria: Implications for Human Health," presented as part of the Experimental Biology '99 meeting in Washington, D.C., in April 1999 and published as a supplement to The Journal of Nutrition. Guest editor for the supplement was Douglas DiRienzo, National Dairy Council, Rosemont, Ill.



In case you lost track of the zeros, that's 100 trillion. That's the number of cells accumulated by bacterial populations at all sites of the human body. For perspective, bacteria exceed the number of cells in the human body by a 10 fold count.

Studies have determined that microbial colonization is not necessary for human survival. However, animals that are germ-free have proven more susceptible to infection than animals with conventional germ populations.

Susceptibility to infection has been attributed to poor immune function and lack of "colonization resistance."

Establishing that colonizing microflora have a major impact on nor mal human health is not the same as the claim of probiotic proponents that supplying exogenous microorganisms (those provided by food or an agent outside the organism) to the intestines will have a positive health benefit. The latter is the ultimate goal of most current probiotic research.
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Author:Pehanich, Mike
Publication:Food Processing
Geographic Code:00WOR
Date:Jun 1, 2001
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