The human body harbours a large variety of microbial communities. It is already well-known that these communities play an important role in human health. Therefore, microbial imbalances can be responsible for several health disorders by different mechanisms. In recent years, probiotic bacteria have been increasingly applied to restore imbalances and stimulate microbiome functions such as immune modulation. Tablets are the dosage form of choice for oral probiotics. Nevertheless, a probiotic tablet with a sufficient amount of viable cells remains a challenge due to the stress of the compression process. Recent research demonstrated that the applied pressure and tableting properties play an important role in the survival of Lacticaseibacillus rhamnosus GG during direct compression. This study focused on the importance of the cell surface molecules in the protection of this prototype probiotic strain during direct compression. Spray-dried powders of L. rhamnosus GG and its exopolysaccharide-deficient mutant and lipoteichoic acid mutant were blended with two different filler-binders and compacted at various compression pressures. Under each tableting condition, the survival rate and tableting properties were analysed. The results demonstrated that the cell surface molecules play an important role in the behaviour of L. rhamnosus GG during direct compression. Specifically, the long, galactose-rich exopolysaccharides of L. rhamnosus served a protective shield during tablet production, promoting the survival rate of this probiotic strain. The D-alanylation of the lipoteichoic acids plays also an important role. When the D-alanyl ester content was completely absent, the survival rate was less affected by the tableting properties. Moreover, this research revealed that the sensitivity to the tableting properties is species and strain dependent. Copyright © 2020 Elsevier B.V. All rights reserved.