The hype over probiotics is obvious, as packaging advertises their inclusion in food products in almost every grocery store. Yet probiotics have been a part of the human diet for thousands of years, though they were unknown until the 19th century. Before the discovery of probiotic microbes, however, people ate probiotics in fermented foods and drinks that included wine, yogurt, cheese, beer, kefir, kimchi, and sauerkraut. In fact, Pliny the Elder, an ancient Roman naturalist, prescribed fermented milk to treat intestinal problems.

Knowledge about probiotics started to deepen in the 1890s. When throughout the Balkans, Russian zoologist Ilya Ilyich Metchnikoff noted that people in rural Bulgaria lived noticeably longer than much wealthier European city dwellers, with many living over 100 years despite harsh climates and severely impoverished conditions. He found that a staple of their diet, a type of soured milk (essentially yogurt), largely contributed to their extended lifespans. After some research, Metchnikoff concluded that this was due to the lactic acid in a type of Lactobacillus bacteria that helped ferment this yogurt.

In the 1990s, scientists began to research the microbiome within the human digestive system, looking at how the microbes people eat affected their health. The early 21st century saw the World Health Organization (WHO) issue a formal definition for probiotics, kickstarting research that led to discoveries about how different microbial strains affect the body. Certain microbial strains or species are not beneficial for health, whereas others are. This led to the use of the term “probiotic” to describe beneficial bacteria in the gut. Today’s probiotics offer numerous benefits beyond their forebears, which has led to food processing companies and supplement manufacturers looking into producing probiotics for their products. 

Why Are Probiotics Important? 

Before looking into how probiotics are manufactured, it’s essential to understand why probiotics are so important. Defined by the WHO as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host," probiotics are found in various foods and supplements. When consumed in the right amounts, they’ve been proven to assist with digestion, sustain the body’s immune system, heighten metabolism, and provide other health benefits.

Since the early 2000s, scientific studies have corroborated what both Pliny the Elder and Ilya Ilyich Metchnikoff recognized: that probiotics positively affect human health. This has led to the development of various food products, most of which utilize fermented milk as a basis for probiotic fabrication. Probiotics can be incorporated not just into yogurt-like foods but also into dry food matrices and dietary supplements, many of which remain stable for up to two years.

How Are Probiotics Manufactured? 

To make a high-quality probiotic suitable for consumers, the process for manufacturing probiotics requires expertise, advanced equipment, and a modern processing environment. Production differs according to the formulated product, strains, and processing methods. Though considered dietary supplements, the methods for making probiotics are different.

The Steps: How Are Probiotics Manufactured? 

Manufacturing probiotics can be divided into five basic steps, though quality testing should be included throughout the process.

These include:

Selecting a Strain

Strain selection depends on the health issues it’s meant to resolve; for example, aiding digestion, fortifying the immune system, or relieving stress. Probiotics should also be able to survive within the stomach’s acidic conditions.

Commonly used strains in probiotic manufacturing include:

  • Lactobacillus: These strains produce lactic acid, one of the hundreds of probiotic species found within the human body.

Its benefits include: 

  • Augments mineral bioavailability
  • Encourages growth factors
  • Fosters immune functions
  • Generates lactic acid and hydrogen peroxide
  • Maintains beneficial levels of Candida albicans
  • Minimizes intestinal absorbency
  • Stabilizes intestinal mucosal barrier
  • Sustains necessary equilibrium of bacterial types
  • Bifidobacterium: Like Lactobacillus, these bacteria produce lactic acid. They colonize the colon and help create a microbial barrier against adverse bacteria. Certain species keep detrimental bacteria from attaching by binding themselves to the intestinal mucosal barrier.
  • Bacillus: This genus forms a spore-like protein coating around it, enabling it to survive intact through stomach acids. The proteins that form this protective envelope allow them to germinate and multiply once they reach the small intestine. They’re even able to withstand bile, so they can also survive in the small intestine.  
  • Streptococcus: Used in the dairy industry, Streptococcus thermophilus helps ferment yogurt and multiple types of cheese.

Formulating Media

When considering the correct measurements of raw material for an effective probiotic formula, the strains must resist both stomach acids and bile to survive through the stomach and into the intestinal tract. Once the strains are chosen, they must ferment and stabilize the strain to control what nutrients and parameters will optimize growth, after the establishment of which large scale production can begin.

Fermenting Raw Material

Bacteria cultivation takes up to six weeks and must be specially produced to preserve the quality and freshness of each order. Cultivation can’t be rushed, and once it’s begun, there’s no way to source an identical strain from another supplier, as strain identification numbers are specific to raw material suppliers. 

In fermentation, all equipment must be sterilized to prevent contamination. Once added to  the media, the strain multiplies within a bulk tank, where a warm and nutrient-rich bath nurtures the bacterial colony until it reaches its required count. This is when by-products called metabolites form as bacteria metabolize the nutrients.

Separation & Drying

The metabolites and probiotic strains are separated via a centrifuge, and probiotic stability requires close watch, as they lose freshness as soon as they’re packaged. The probiotic bacteria are cooled to very low temperatures, after which they’re dried in an environment that’s neither too hot nor humid. Probiotics can either be freeze-dried or spray-dried. These processes transform the probiotic into a dry powder.

Blending & Packaging

Though this process results in a powder containing only one strain, other probiotic powders can be blended together to make multi-strain formulas with a balanced and uniformly dispersed amalgam.

Other ingredients that can go into the mixture include: 

  • Binders for producing alternate forms of dosage
  • Complementary ingredients with a similar health focus
  • Flavoring ingredients
  • Prebiotics that support probiotic growth within the body

Once properly blended, the ingredients are formed into capsules, powders, or tablets. Probiotic expiration dates differ depending on the bacterial strain. They’re also highly sensitive to humidity, light, and temperature, so they should be packed and shipped with care so they’re not exposed to moisture, direct sunlight, or high temperatures.

Which Machine Do I Need?

The Equipment: How Are Probiotics Manufactured?

When considering how probiotics are manufactured, the equipment used in the production process must ensure both stability and high yield while safeguarding against certain allergens. The most important aspect of probiotic fabrication involves making processes consistent and reproducible to guarantee probiotic performance and the quality of the final product. This requires specific equipment customized for probiotic production, much of which is used by the pharmaceutical industry or for manufacturing nutraceuticals.  

Depending on the exact processes employed, manufacturers may need the following: 

  • Formulation tanks where nutrients and water are mixed to prepare it as a media to promote fermentation.  
  • Autoclave or other sterilization equipment to disinfect the nutrient-rich media at high temperatures before continuing to fermentation.
  • Bioreactor or fermenter that controls temperature, pH, oxygen levels, and other environmental conditions during the fermentation process to form bacterial colonies from media.  
  • Centrifuge with a sieve that separates probiotic bacteria from spent media, sieving off the concentrate for the next processing stage while filtering out permeate.
  • Concentrate vessels in which cryoprotectants or lyoprotectants are added to protect probiotic bacteria during freezing or freeze-drying processes.
  • Pelletizer that forms the solid biomass into pellet form.
  • Feeder valve to regulate flow of pellets on to where they’re frozen or freeze-dried.  
  • Freeze dryer or other drying equipment to remove moisture from probiotic pellets.

Commercially manufacturing probiotics requires manufacturers to understand the sensitivities of the strains. This will involve testing production methods in a lab setting. Scaling up often offers significant challenges, as controlling each process during largescale production is more difficult. For example, while centrifugation may take mere minutes in the lab, commercial production may take many hours due to the huge volume of processed probiotics. For this reason, a system's testing should be done before establishing it in an industrial environment.

How Are Probiotics Manufactured with Prater Machinery?

Prater Industries builds equipment and systems for the pharmaceutical and nutraceutical industries, both sister sectors to the probiotic industry. Prater’s centrifugal rotary sifters act as sieves for separating probiotic bacteria from spent media. Before the freeze-drying phase of production, Prater’s rotary airlock feeder valves can feed and meter pelleted probiotics from the pelletizer. Please contact us today to learn more about how probiotics are manufactured and what other Prater equipment can be utilized within your specific system.