Researchers from Meiji and the University of Tokyo had previously demonstrated that the administration of heat-killed OLL2712 cells managed to suppress chronic inflammation and improve hyperglycaemia in obese, diabetic mice.
Tested on humans
For the current study, they sought to preliminarily examine the impact of OLL2712 supplementation on glucose metabolism and chronic inflammation in pre-diabetic human subjects.
They recruited 30 participants (22 men and eight women), aged 52 to 61, for a 12-week prospective, single-arm open trial, and a four-week post-treatment period afterwards.
All subjects were required to have fasting plasma glucose levels of 105mg/dL to 130mg/dL. They also had no diseases or food allergies, had not consumed excessive amounts of alcohol within the last three months, and did not regularly consume yogurt, beverages containing lactic acid bacteria, or probiotic supplements more than twice a week.
Every day for 12 weeks, each study subject was given 100g of a dairy beverage containing over 1,000 heat-killed OLL2712 cells.
Throughout the supplementation period, they were asked to maintain their regular diet and lifestyle habits. They were also given life diaries to record their compliance and report any issues, and interviewed at each clinic visit by a physician who mainly monitored subject compliance.
After overnight fasting, their blood samples were drawn and used to analyse their glycated haemoglobin (HbA1c), plasma glucose, serum glycoalbumin, total, LDL and HDL cholesterol, triglycerides, and non-esterified fatty acids (NEFA).
The researchers also measured their serum insulin levels and blood pressure. They subsequently found that the subjects' fasting plasma glucose and glycoalbumin levels were markedly lower after four and eight weeks of treatment, respectively.
However, these improvements were not seen after the treatment period, though the study did not specify how long after.
Yet when it came to chronic inflammation, serum levels of the pro-inflammatory cytokine MCP-1 (monocyte chemoattractant protein 1) was shown to have been significantly lowered after four, eight and 12 weeks of treatment, as well as after the treatment period.
Serum levels of another pro-inflammatory cytokine, IL-6 (interleukin-6), were markedly reduced after eight weeks of treatment, though they tended to be even lower after four weeks of treatment.
However, other cytokine levels did not see any notable changes throughout the study. As MCP-1 and IL-6 are both secreted in abundance from adipose tissue in the presence of chronic inflammation, the researchers wrote that "OLL2712 ingestion might suppress chronic inflammation in the adipose tissue".
Placebo needed for pre-diabetics
The researchers noted the most important limitation of the trial: the absence of a placebo group. They said, however, that they had "considered that this study could preliminarily evaluate the functionality of OLL2712 cells".
They explained that without intervention, pre-diabetics were known to develop increasingly worsening insulin resistance, resulting in higher blood glucose levels, but added that previous clinical trials had found these levels tended to be even higher during the intake period in the placebo group.
They also reported that the improvements they had observed in the subjects during the study were no longer seen after they had stopped ingesting the OLL2712 cells.
They concluded: "The results of this study suggested that the ingestion of heat-killed OLL2712 cells have the potential to improve insulin resistance and glucose metabolism in human pre-diabetic subjects.
"The ingestion of OLL2712 cells also suppressed serum MCP-1 and IL-6 levels, which are pro-inflammatory cytokines involved in the development of insulin resistance and hyperglycaemia. In addition, the result of the stratified analysis suggested that OLL2712 cells might exert anti-diabetic effects by suppressing chronic inflammation.
"(However) placebo-controlled trials are needed to prove the efficacy of OLL2712 cells. Based on the results of this study, we plan to conduct further studies with a randomised, double-blind, placebo-controlled design."
"Effects of 12-week Lactobacillus plantarum OLL2712 treatment on glucose metabolism and chronic inflammation in human pre-diabetic subjects: A single-arm pilot study"
Authors: Takayuki Toshimitsu, et al.